@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&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&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 & visual science},
volume = {67},
number = {3},
pages = {41},
doi = {10.1167/iovs.67.3.41},
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).

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 × 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 µm 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.

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.

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.},
}

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

@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},
doi = {10.2196/79699},
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.

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.

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.

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.

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.},
}

Humans
Female
Male
Aged
Middle Aged
*Self-Examination/methods
*Macular Degeneration/diagnosis
*Vision Disorders/diagnosis
Diabetic Retinopathy/diagnosis
Aged, 80 and over
*Mobile Applications

@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 = {},
number = {},
pages = {127968},
doi = {10.1016/j.envpol.2026.127968},
pmid = {41850516},
issn = {1873-6424},
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 glial 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 microns 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 = {},
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 {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 & 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.

METHODS:  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 G needle and one with a 40 G needle-either to the fellow eye on the same day or to the same eye one month apart. Injections (0.05 mL bevacizumab, ranibizumab, or aflibercept) were administered in an operating room by a single surgeon following Avery et 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.

RESULTS:  Mean age was 69.3 ± 11.5 years; 69 % were men. VAS pain scores were significantly lower with 40 G needles than with 30 G needles (2.33 ± 1.26 vs 4.02 ± 1.73; mean paired difference -1.69 ± 0.33; p < 0.001). Median VR grade declined from 2 (IQR 2-3) to 0 (IQR 0-1) with 40 G needles (p < 0.001). SCH grade did not differ between gauges (median 0, IQR 0-1; p = 0.93). No injection related adverse events occurred.

CONCLUSIONS:  Using an ultrathin 40 G needle for IVIs significantly reduces patient‑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.

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.

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 < 0.0001). In adjusted models, male sex (OR = 2.00, 95% CI 1.02-4.00) and lower income were strongly associated with referable AMD prevalence; race and age were not.

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.

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 & visual science},
volume = {67},
number = {3},
pages = {37},
doi = {10.1167/iovs.67.3.37},
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.

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.

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).

CONCLUSIONS: The NOTCH3 R544C variant may be associated with an increased risk of AMD, warranting further studies to clarify the underlying mechanisms.},
}

Humans
*Receptor, Notch3/genetics/metabolism
Female
Male
Taiwan/epidemiology
*Macular Degeneration/genetics/epidemiology
Middle Aged
Aged
Registries
Risk Factors
Biological Specimen Banks
Prevalence
*Mutation

@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 & visual science},
volume = {67},
number = {3},
pages = {36},
doi = {10.1167/iovs.67.3.36},
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).

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°, 2°, and 9° eccentricities (plateau set at 9°). Generalized linear mixed-effects models assessed associations of MPOV with OCT biomarkers and qCSF metrics.

RESULTS: Lower MPOV values were associated with reduced ONL thickness (β*, 0.343-0.424; all P < 0.01), presence of hDCs (β*, -0.80 to -0.60; all P < 0.01), and iRORA at 1° (β*, -0.43; P = 0.03). MPOV at all eccentricities was associated with lower AULCSF (β*, 0.32-0.45), CA (β*, 0.38-0.48), and CS at 3 cpd and 6 cpd (β*, 0.39-0.69; all P < 0.05), but not with VA (β*, 0.10-0.28; all P > 0.05).

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.},
}

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

@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},
abstract = {PURPOSE: To evaluate associations between social determinants of health (SDOH) and treatment rates among patients with exudative age-related macular degeneration (exAMD).

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.

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).

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 & 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.

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.

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 × 3-mm and 6 × 6-mm angiograms, and significantly increased FAZ area and FAZ perimeter on 6 × 6-mm angiograms. There was no difference on 12 × 12-mm angiograms. Compared to controls, AOFVD eyes had significantly reduced FAZ circularity on 3 × 3-mm angiograms.

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 & 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).

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.

RESULTS: Patients were followed for 2.5 ± 0.3 years. Central subfield thickness decreased from 267.6 ± 61.0 µm to 225.8 ± 42.1 µm (P < .001), and treatment intervals extended from 6.5 ± 2.4 to 11.5 ± 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.

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},
doi = {10.3346/jkms.2026.41.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.

METHODS: This cross-sectional study, based on data from the Korea National Health and Nutrition Examination Survey (2017-2021), included 15,030 subjects aged ≥ 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.

RESULTS: Among the four groups, the GA group showed highest mean age (72.47 ± 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 ± 0.02 vs. 0.93 ± 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 ± 3.70 vs. 20.35 ± 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.

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.},
}

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

@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 & 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.

BACKGROUND: This study explored the socioeconomic impact of low vision and blindness, mainly due to untreatable bilateral eye diseases, on individuals and their households.

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.

RESULTS: A total of 110 patients (mean age 51.4 ± 14.6 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 < 0.001). The primary monthly income of patients decreased significantly (p < 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 years (adjusted odds ratio [AOR] 10.7, 95% CI: 1.2-96.0, p = 0.035), 51-60 years (AOR 8.4, 95% CI: 1.2-59.9, p = 0.034), and over 60 years (AOR 46.5, 95% CI: 4.8-445.6, p < 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.

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 {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.

PATIENTS AND METHODS: This retrospective, two-center study included 32 eyes undergoing PPV with subretinal tPA (25-50 µg/0.1-0.2 mL) and SF6 or air tamponade, followed for ≥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.

RESULTS: Mean patient age was 60.8 ± 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 ± 0.30 to 0.56 ± 0.26 logMAR (P<0.001), with 55.2% gaining ≥3 lines. CMT reduced from 501 ± 219 to 276 ± 70 µm (P<0.001), and SMH size decreased from 5 ± 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.

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.},
}

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

@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 & visual science},
volume = {67},
number = {3},
pages = {35},
doi = {10.1167/iovs.67.3.35},
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.},
}

*Awards and Prizes
Humans
*Ophthalmology/history
History, 21st Century
History, 20th Century
*Macular Degeneration/history
United States

@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 & visual science},
volume = {67},
number = {3},
pages = {34},
doi = {10.1167/iovs.67.3.34},
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.},
}

Humans
*Macular Degeneration/physiopathology/diagnosis
*Dark Adaptation/physiology
*Retinal Rod Photoreceptor Cells/physiology
Retinal Pigment Epithelium/pathology
Awards and Prizes
Tomography, Optical Coherence

@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 & visual science},
volume = {67},
number = {3},
pages = {33},
doi = {10.1167/iovs.67.3.33},
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.},
}

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

@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 {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).

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.

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 ± 0.43 logMAR, range: 0-1.8) and the day of IOI diagnosis (0.67 ± 0.52, range: 0-2.3) (p < 0.001). VA after IOI resolution showed no significant difference from baseline (p > 0.99). Intravitreal injections were resumed in 42 eyes. IVFs re-challenge was attempted in 9 eyes, with 5 developing another episode of IOI.

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 {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 {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 & 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 {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 = {},
doi = {10.3390/ijms27052516},
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.},
}

Humans
*Protein Processing, Post-Translational
*Eye Diseases/metabolism/therapy
Animals
*Lactic Acid/metabolism
Lysine/metabolism
Signal Transduction

@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 = {},
doi = {10.3390/diagnostics16050656},
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 {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 = {},
doi = {10.3390/jcm15052031},
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 {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 = {},
doi = {10.3390/jcm15051686},
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 {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 {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.

METHODS: Retrospective observational study conducted in a tertiary hospital (March 2024-March 2025). Patients receiving faricimab (treatment-naïve or pre-treated with anti-VEGF therapy), with ≥1 post-loading dose, were included. Dosing intervals were analyzed at baseline, 6 and 12 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.

RESULTS: We included 129 patients (148 eyes), mean age 74.5 ± 8.85 years; 55% were female. A total of 39 patients (30.2%) were treatment-naïve and 90 (69.8%) were pretreated. At 12 months, 48.8% of naïve and 55.5% of pretreated patients achieved 8-12 weeks intervals. Mean persistence was 12.2 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 months. Only one patient discontinued due to inefficacy. No serious adverse events or endophthalmitis occurred.

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 {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.

DESIGN: Retrospective, interventional case series SUBJECTS: Patients with phakic lens status in both eyes at baseline who received ≥12 unilateral anti-VEGF injections.

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.

MAIN OUTCOME MEASURES: Hazard ratio (HR) and 95% confidence interval (CI) for incident cataract surgery in the injected eye, compared with the fellow eye.

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.

CONCLUSION: Long-term intravitreal anti-VEGF treatment was associated with a significantly increased risk of developing cataract for which surgical intervention was performed.},
}

@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 {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.

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' κ and sensitivity, and specificity were computed for four major pathologies.

RESULTS: Among 202 eyes (mean age 62.7 ± 12.3 years), RS inter-agreement was moderate for diagnosis (overall κ = 0.59) and referral (κ = 0.47). NRS showed substantial (NRS1 κ = 0.78) to moderate (NRS2 κ = 0.64; NRS3 κ = 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 (κ = 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.

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 {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 {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 {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).

DESIGN: Retrospective cohort study using a multicenter, real-world electronic health record database.

SUBJECTS: Adults aged ≥18 years diagnosed with PXG (study group) or POAG (control group).

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.

MAIN OUTCOME MEASURES: The primary outcome was the development of CSCR within 1- and 5-year follow-up periods following the glaucoma diagnoses.

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 = 0.036) at the 1-year follow-up and 1.631 (95% CI, 1.014-2.622; p = 0.044) at 5 years.

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 {pmid41818453,
year = {2026},
author = {Prenner, S and Fine, HF and Do, DV},
title = {Photobiomodulation for Dry Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {57},
number = {3},
pages = {146-148},
doi = {10.3928/23258160-20251125-02},
pmid = {41818453},
issn = {2325-8179},
}

@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 & 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.

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.

RESULTS: In total, 25 patients with RAO (14 women and 11 men, 71.5 ± 8.9 years) and 19 healthy individuals (10 women and 9 men, 69.0 ± 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).

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.},
}

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

@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.

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.

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.

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 {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 {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.

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.

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.

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 {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.

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.

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.

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.

https://www.crd.york.ac.uk/prospero/, identifier CRD420231132016.},
}

@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 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 GLP Toxicology study in NHP 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 {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 {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 {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 {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 {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.

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.

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 {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.},
}

Humans
*Macular Degeneration/immunology/microbiology/metabolism
*Gastrointestinal Microbiome/immunology/physiology
Animals
Dysbiosis/immunology
*Retina/immunology/metabolism/pathology

@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.

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.

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.

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.},
}

*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

@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.

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: ≥ 150 min/week (primary) and ≥ 300 min/week (secondary). Participants were categorized as: inactive (below threshold), weekend warriors (WW; meeting threshold with ≥ 50% MVPA concentrated within 1-2 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 years.

RESULTS: At the ≥ 150 min/week threshold, both WW (hazard ratio [HR] = 0.89, 95% confidence interval [CI]: 0.84-0.94, P < 0.001) and regularly active patterns (HR = 0.93, 95% CI: 0.87-0.99, P = 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 = 0.74, 95% CI: 0.55-0.99, P = 0.043) and age-related macular degeneration (AMD, HR = 0.85, 95% CI: 0.75-0.97, P = 0.016). Direct comparisons between the WW and regularly active patterns showed no significant differences for these conditions (all P > 0.05), except for a nominal difference in glaucoma (P = 0.036). At the ≥ 300 min/week threshold, only the WW pattern remained significantly associated with reduced risk of cataract (HR = 0.91, 95% CI: 0.86-0.97, P = 0.002) and glaucoma (HR = 0.86, 95% CI: 0.75-0.97, P = 0.019).

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 {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.

METHODS: Retrospective study of 170 eyes characterising GA lesions using near infrared (NIR) and spectral domain optical coherence tomography (SD-OCT).

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  μm (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 mm/yr SQRT, SD 0.21). Bilateral disease (p = 0.005), reticular pseudodrusen (p = 0.02), larger baseline GA area (p < 0.001) and multifocal disease (p = 0.01) were independently associated with greater odds of rapid GA progression.

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 {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.

METHODS: nAMD patient-eyes that received ≥1 faricimab injection after May 2022 at one of 35 participating UK National Health Service retinal clinics with ≥12 months of follow-up after faricimab initiation as of July 2024 were included. Treatment-naïve (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.

RESULTS: 5854 nAMD patients (6991 eyes; 26.5% TN, 73.5% PT) were included. 83.3% of PT eyes switched from aflibercept 2.0 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.

CONCLUSIONS: These 1-year data support real-world faricimab effectiveness, durability, and safety in 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 {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 = {},
number = {},
pages = {},
pmid = {41805864},
issn = {2731-7218},
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.

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 focus on xenobiotics.

RESULTS: The findings demonstrate a distinct yet complex influence of systemic signals: a 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.

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 {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 & visual science},
volume = {67},
number = {3},
pages = {19},
doi = {10.1167/iovs.67.3.19},
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.

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.

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.

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.},
}

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

@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 & technology},
volume = {15},
number = {3},
pages = {10},
doi = {10.1167/tvst.15.3.10},
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.

METHODS: This retrospective study analyzed treatment-naïve 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.

RESULTS: Sixty‑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).

CONCLUSIONS: Quantitative OCTA biomarkers distinguish CNV etiologies and activity, providing a noninvasive, objective basis for clinical assessment and individualized treatment planning.

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.},
}

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

@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 = {},
number = {},
pages = {1-16},
doi = {10.1080/17460441.2026.2635492},
pmid = {41805144},
issn = {1746-045X},
abstract = {INTRODUCTION: Vision loss in older adults is largely driven by age-related macular degeneration (AMD), characterized by progressive damage 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.

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.

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 {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 {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 {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},
doi = {10.1371/journal.pone.0340477},
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.},
}

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

@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.

DESIGN: Reader study.

PARTICIPANTS: One hundred seventy-one pairs of CFP and FAF images from 60 eyes of 53 individuals.

METHODS: High-density, targeted microperimetry testing (with Goldmann Size III stimuli) was performed twice per visit in a 3.5° (approximately 1000 μm) 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.

MAIN OUTCOME MEASURES: Prevalence of a repeatable ≤10 dB defect for CFP- and FAF-defined GA ≥175 μm, and the minimum lesion size showing a ≥90% prevalence of a repeatable ≤10 dB defect (deemed characteristic of regions with a truly nonresponding test location on microperimetry).

RESULTS: Color fundus photograph-defined GA1 and GA2 and FAF-defined GA ≥175 μm were graded as present in 13%, 31%, and 41% of images, respectively, and 77%, 67%, and 62% lesions, respectively, had a repeatable ≤10 dB defect. Only CFP-defined GA1 ≥625 μm, CFP-defined GA2 ≥650 μm, and FAF-defined ≥675 μm had a ≥90% prevalence of a repeatable ≤10 dB defect.

CONCLUSIONS: Color fundus photograph and FAF-defined GA lesions ≥175 μm do not show the same functional characteristics as regions with a truly nonresponding test location, and only much larger lesions (approximately ≥650 μm) showed such similar functional characteristics. These findings provide crucial insights when considering CFP- and FAF-defined atrophic endpoints for clinical studies.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}

@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.

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.

SUBJECTS: We enrolled Whites aged 18 to 64 years with no clinical signs of AMD.

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.

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.

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.

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.

FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.},
}

@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.

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.

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.

CONCLUSIONS: This first phased atlas uncovers GM effects over the AMD course, identifying potential microbial and biochemical targets for intervening in disease development.},
}

Humans
*Gastrointestinal Microbiome/genetics/immunology
*Macular Degeneration/genetics/microbiology/immunology/pathology
Mendelian Randomization Analysis
Genome-Wide Association Study
Disease Progression
Polymorphism, Single Nucleotide

@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 {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).

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.

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.

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 {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 {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.},
}

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

@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 {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 {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 {pmid41016571,
year = {2025},
author = {Kao, CC and Chokkalingam, U and Singh, A and Shih, PC and Prakash, E and Wang, JS},
title = {Protective effects of acemannan-enriched Aloe polysaccharide J2 against UVA-induced autophagic cell death in retinal pigment epithelial cells.},
journal = {European journal of pharmacology},
volume = {1006},
number = {},
pages = {178199},
doi = {10.1016/j.ejphar.2025.178199},
pmid = {41016571},
issn = {1879-0712},
mesh = {*Ultraviolet Rays/adverse effects ; *Retinal Pigment Epithelium/cytology/drug effects/radiation effects/metabolism/pathology ; Humans ; *Aloe/chemistry ; *Autophagy/drug effects/radiation effects ; Reactive Oxygen Species/metabolism ; *Mannans/pharmacology ; Cell Line ; *Polysaccharides/pharmacology ; Cytoprotection/drug effects/radiation effects ; Mitogen-Activated Protein Kinases/metabolism ; },
abstract = {Age-Related Macular Degeneration (AMD) is one of the leading causes of irreversible vision loss worldwide, characterized by the degeneration of the retinal pigment epithelium (RPE) and photoreceptor cells, resulting in progressive loss of central vision. RPE cells are highly specialized and essential for retinal function, and their malfunction due to genetic, environmental, or age-related factors contributes significantly to AMD pathogenesis. Ultraviolet A (UVA) radiation is recognized as a major causative factor, as it induces the accumulation of reactive oxygen species (ROS) in RPE cells, ultimately contributing to the development of AMD. On the other hand, acemannan, a D-isomer mucopolysaccharide derived from Aloe vera pulp, is known for its antioxidant and anti-inflammatory properties. In this study, we extracted a highly purified Aloe-derived polysaccharide fraction enriched in acemannan, designated Aloe polysaccharide J2 (ACJ2), to investigate its protective effects against UVA-induced RPE damage. The results showed that post-treatment with ACJ2 significantly reduced UVA-induced cell death by lowering mitochondrial ROS levels, suppressing phosphorylation of mitogen-activated protein kinases (MAPKs), including p38 MAPK, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK), and downregulating proinflammatory mediators including tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and inducible nitric oxide synthase (iNOS). Furthermore, ACJ2 enhanced heme oxygenase-1 (HO-1) expression and mitochondrial DNA levels, and inhibited p62/sequestosome-1 (p62) consumption and microtubule-associated protein 1 light chain 3 (LC3)-I/II conversion, thereby reducing autophagic flux. These findings demonstrate that ACJ2 mitigates UVA-induced damage and restores disrupted autophagy in RPE cells, supporting its potential as a therapeutic candidate for AMD.},
}

*Ultraviolet Rays/adverse effects
*Retinal Pigment Epithelium/cytology/drug effects/radiation effects/metabolism/pathology
Humans
*Aloe/chemistry
*Autophagy/drug effects/radiation effects
Reactive Oxygen Species/metabolism
*Mannans/pharmacology
Cell Line
*Polysaccharides/pharmacology
Cytoprotection/drug effects/radiation effects
Mitogen-Activated Protein Kinases/metabolism

@article {pmid41006433,
year = {2025},
author = {Bradley, A and Park, S and Park, S and Kim, K and Galdamez, A and Min, H and Diaz-Aguilar, MS and Hartnett, ME and Lee, EJ and Lin, JH},
title = {Targeting ATF6 reduces pathological neovascularization and improves visual outcomes in retinal disease models.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {33070},
pmid = {41006433},
issn = {2045-2322},
support = {R01 EY015130/EY/NEI NIH HHS/United States ; P30 EY026877/EY/NEI NIH HHS/United States ; Merit I01BX002284//U.S. Department of Veterans Affairs/ ; DISC2-10973//California Institute for Regenerative Medicine/ ; P30EY026877/NH/NIH HHS/United States ; I01 BX002284/BX/BLRD VA/United States ; },
mesh = {Animals ; *Activating Transcription Factor 6/metabolism/genetics/antagonists & inhibitors ; Mice ; *Retinal Neovascularization/metabolism/pathology/genetics ; Disease Models, Animal ; Unfolded Protein Response/genetics ; Mice, Knockout ; Signal Transduction ; Retinopathy of Prematurity/metabolism/pathology ; Retina/metabolism/pathology ; Mice, Inbred C57BL ; Cell Proliferation ; },
abstract = {Pathological retinal neovascularization is a cause of vision loss in diseases including retinopathy of prematurity (ROP), wet age-related macular degeneration (AMD), and diabetic retinopathy. The Unfolded Protein Response (UPR) is an intracellular signal transduction mechanism that is activated by ER stress and upregulates many proteins, including angiogenesis factors like VEGF and HIF-1α. This suggests that UPR genes and pathways may drive retinal angiogenesis. Here, we tested the role of the UPR regulator Activating Transcription Factor 6 (ATF6) in pathological and developmental retinal angiogenesis. We induced pathological retinal neovascularization in Atf6[-/-] mice using the oxygen-induced retinopathy (OIR) model and found significantly preserved visual function, accompanied by decreased retinal neovascularization, endothelial cell proliferation, and UPR transcriptional program induction. When we chemically blocked ATF6 signaling by intraocular injection of the small molecule Ceapin-A7, we also saw suppressed retinal expression of UPR genes. Additionally, in postnatal day 7 Atf6[-/-] mice when the retinal vasculature is developing in response to physiologic intraocular hypoxia, there was a transient but significant defect in pruning and retinal blood vessel extension. Together, our results demonstrate ATF6's causal role in developmental and pathological retinal angiogenesis and highlight its potential as a therapeutic target to preserve vision in retinal neovascularization diseases.},
}

Animals
*Activating Transcription Factor 6/metabolism/genetics/antagonists & inhibitors
Mice
*Retinal Neovascularization/metabolism/pathology/genetics
Disease Models, Animal
Unfolded Protein Response/genetics
Mice, Knockout
Signal Transduction
Retinopathy of Prematurity/metabolism/pathology
Retina/metabolism/pathology
Mice, Inbred C57BL
Cell Proliferation

@article {pmid40973777,
year = {2025},
author = {Hogg, HDJ and Talks, SJ and Engelmann, J and Teare, MD and Pogose, M and Patel, PJ and Balaskas, K and Maniatopoulos, G and Keane, PA},
title = {Dual site external validation of artificial intelligence-enabled treatment monitoring for neovascular age-related macular degeneration in England.},
journal = {Eye (London, England)},
volume = {39},
number = {16},
pages = {2973-2979},
pmid = {40973777},
issn = {1476-5454},
support = {NIHR301467//DH | National Institute for Health Research (NIHR)/ ; },
mesh = {Humans ; *Artificial Intelligence ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; England ; *Angiogenesis Inhibitors/therapeutic use ; Aged ; Male ; Female ; Intravitreal Injections ; Ranibizumab/therapeutic use ; Aged, 80 and over ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Subretinal Fluid ; },
abstract = {BACKGROUND: Monitoring neovascular age-related macular degeneration (nAMD) is a significant contributor to ophthalmology demands in the NHS, with clinical capacity struggling to meet the demand. This task depends upon interpreting retinal optical coherence tomography (OCT) imaging, where artificial intelligence (AI) could rebalance clinical demand and capacity. However, evidence of safety and effectiveness in nAMD monitoring is lacking.

METHODS: Using a published non-inferiority design protocol, 521 pairs of ipsilateral retinal OCTs from consecutive visits for nAMD treatment were collected from two NHS ophthalmology services. Real-world binary assessments of nAMD disease activity or stability were compared to an independent ophthalmic reading centre reference standard. An AI system capable of retinal OCT segmentation analysed the OCTs, applying thresholds for intraretinal and subretinal fluid to generate binary assessments. The relative negative predictive value (rNPV) of AI versus real-world assessments was calculated.

RESULTS: Real-world assessments of nAMD activity showed a NPV of 81.6% (57.3-81.6%) and a positive predictive value (PPV) of 41.5% (17.8-62.3%). Optimised thresholds for intraretinal fluid increase (>1,000,000 µm³) and subretinal fluid increase (>2,000,000 µm³) for the AI system assessments produced an NPV of 95.3% (85.5-97.9%) and PPV of 57.8% (29.4-76.0%). The rNPV of 1.17 (1.11-1.23) met predefined criteria for clinical and statistical superiority and accompanied an rPPV of 1.39 (1.10-1.76).

CONCLUSIONS: This study suggests that the same thresholds for interpreting OCT-based AI analysis could reduce undertreatment and overtreatment in nAMD monitoring at different centres. Interventional research is needed to test the potential of supportive or autonomous AI assessments of nAMD disease activity to improve the quality and efficiency of services.},
}

Humans
*Artificial Intelligence
Tomography, Optical Coherence/methods
*Wet Macular Degeneration/drug therapy/diagnosis
England
*Angiogenesis Inhibitors/therapeutic use
Aged
Male
Female
Intravitreal Injections
Ranibizumab/therapeutic use
Aged, 80 and over
Visual Acuity
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Subretinal Fluid

@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 & 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).

METHODS: Thirty-four adults with AMD, 64.7% female, mean age 80.2(±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.

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.

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.

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.},
}

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

@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.

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.

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.

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 {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.

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.

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+ model using 39 196 additional images from the US population and tested on 3 datasets, including an external set from Singapore.

EXPOSURE: Age-related macular degeneration risk features.

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.

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+ 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]).

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.},
}

Humans
*Artificial Intelligence
*Workflow
*Macular Degeneration/diagnosis/classification
Female
Male
Aged
*Eye Diseases/diagnosis
Reproducibility of Results
Middle Aged

@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.

DESIGN: Retrospective comparative study evaluating three DL architectures on OCT data with two experimental approaches.

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.

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.

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).

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±0.083 and accuracy of 0.831±0.006 using selective B-scans. In GA versus NGA classification, ViT-B/16 attained an AUC-ROC of 0.950±0.002 and accuracy of 0.873±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±0.003 and accuracy of 0.751±0.002 using selective B-scans.

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 {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.

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.

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 = 1.18, FDR adjusted P = 0.01), keratitis (OR = 1.13, P = 0.007), blepharochalasis (OR = 1.23, P = 0.002), and lacrimal system disorders (OR = 1.09, P = 0.04), while decreasing the risk of primary open-angle glaucoma (OR = 0.83, P = 0.003), exfoliation glaucoma (OR = 0.71, P = 0.001), and normotensive glaucoma (OR = 0.79, P = 0.02). Conversely, genetic liability to strabismus increased ADHD risk (OR = 1.09, P = 0.03). The identification of pleiotropic loci using PLACO suggested that genetic factors played a role in the associations between ADHD and ocular diseases.

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.},
}

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

@article {pmid40293961,
year = {2025},
author = {Maniglia, M and Jayakumar, S and Demirayak, P and Maxwell, E and Anand, D and Cortez, J and Vice, JE and Visscher, KM and Seitz, AR},
title = {A Gaze-Contingent Display Framework for Perceptual Learning Research with Simulated Central Vision Loss.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {218},
pages = {},
doi = {10.3791/67596},
pmid = {40293961},
issn = {1940-087X},
support = {R01 EY031589/EY/NEI NIH HHS/United States ; R21 EY033623/EY/NEI NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/physiopathology/rehabilitation ; Eye Movements/physiology ; *Learning/physiology ; Fixation, Ocular/physiology ; *Eye-Tracking Technology ; *Visual Perception/physiology ; },
abstract = {Macular degeneration (MD) is one of the leading causes of vision impairment in the Western world. Patients with MD tend to develop spontaneous eye movement strategies to compensate for their vision loss, including adopting a preferred retinal locus, or PRL, a spared peripheral region that they use more frequently to replace the damaged fovea. However, not all patients are successful in developing a PRL, and even when they do, it might take them months. Currently, no gold standard rehabilitative therapy exists, and MD research is further hindered by issues of recruitment, compliance, and comorbidity. To help address these issues, a growing body of research has used eye tracking-guided, gaze-contingent displays in a simulated central vision loss paradigm in individuals with intact vision. While simulated vision loss is qualitatively different than pathological central vision loss, our framework provides for a highly controlled model through which to study compensatory eye movements and test possible rehabilitation interventions in low vision. By developing a comprehensive framework, rather than relying on isolated and disconnected tasks, we create a cohesive environment where we can test larger-scale hypotheses, allowing us to examine interactions between tasks, assess training effects across multiple measures, and establish a consistent methodology for future research. Furthermore, participants in simulated central vision loss studies show similarities in their oculomotor compensatory behaviors compared to patients with MD. Here, we present a framework for conducting gaze-contingent studies related to simulated central vision loss. We emphasize the utilization of the framework to test behavioral and oculomotor performance of healthy individuals on a wide range of perceptual tasks encompassing different levels of visual processing. We also discuss how this framework can be adapted for training MD patients.},
}

Humans
*Macular Degeneration/physiopathology/rehabilitation
Eye Movements/physiology
*Learning/physiology
Fixation, Ocular/physiology
*Eye-Tracking Technology
*Visual Perception/physiology

@article {pmid40146119,
year = {2025},
author = {Christen, WG and Rist, PM and Moorthy, MV and Smith, DC and Holman, B and Clar, A and Glynn, RJ and Mares, JA and Sobrin, L and Shadyab, AH and Allison, MA and Millen, AE and Manson, JE and Sesso, HD and , },
title = {Cocoa Flavanol Supplementation and Risk of Age-Related Macular Degeneration: An Ancillary Study of the COSMOS Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {143},
number = {5},
pages = {429-437},
pmid = {40146119},
issn = {2168-6173},
mesh = {Humans ; Female ; Aged ; Male ; Double-Blind Method ; *Dietary Supplements ; *Macular Degeneration/prevention & control/epidemiology/diagnosis ; Middle Aged ; *Flavonols/administration & dosage ; Risk Factors ; Aged, 80 and over ; *Cacao ; *Plant Extracts/administration & dosage ; Disease Progression ; Follow-Up Studies ; Incidence ; },
abstract = {IMPORTANCE: Abnormalities of choroidal blood flow in the eye are associated with occurrence of age-related macular degeneration (AMD). Cocoa flavanols show beneficial effects on vascular risk factors in small and short-term trials and may help reduce AMD risk.

OBJECTIVE: To examine whether daily supplementation with cocoa extract, a source of flavanols, prevents the development or progression of AMD.

This was a prespecified ancillary study of the COSMOS (COcoa Supplement and Multivitamins Outcomes Study) trial, a double-blind, placebo-controlled, 2 × 2 factorial randomized clinical trial of a cocoa extract supplement and a multivitamin supplement in the prevention of cardiovascular disease and cancer among 21 442 US adults, including 12 666 women aged 65 years and older and 8776 men aged 60 years and older. The intervention phase was performed from June 2015 through December 2020; data analysis was completed in August 2024.

INTERVENTION: Cocoa extract supplement (500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin) or placebo.

MAIN OUTCOMES AND MEASURES: The primary end point was a composite of incident cases of AMD plus cases of progression to advanced AMD (geographic atrophy, neovascular membrane, retinal pigment epithelium detachment, or disciform scar) among participants with AMD at baseline, based on self-report confirmed by medical record review.

RESULTS: Mean (SD) participant age was 72.1 (6.6) years, and 12 666 participants (59.1%) were female. During a median (IQR) period of 3.6 (3.2-4.2) years of treatment and follow-up, 344 participants (1.6%) experienced a confirmed AMD event (316 incident AMD, 28 progression to advanced AMD). For the primary composite end point, there were 159 cases (1.5%) in the cocoa extract group and 185 cases (1.7%) in the placebo group (hazard ratio [HR], 0.87; 95% CI, 0.71-1.08; P = .21). Separate Cox models fitted because of evidence of nonproportional hazards (P = .048) indicated a 23% decreased risk in the cocoa extract group during the first 2 years of treatment (HR, 0.77; 95% CI, 0.59-1.01), with no added benefit for treatment beyond 2 years (HR, 1.06; 95% CI, 0.76-1.50). Similar time-dependent findings were observed for the secondary trial outcomes of incident visually significant AMD and advanced AMD.

CONCLUSIONS AND RELEVANCE: In this ancillary study of the COSMOS randomized clinical trial, cocoa extract supplementation for a median period of 3.6 years among older women and men had no effect overall on occurrence of AMD. However, a possible modest treatment effect early in the trial could not be ruled out, which warrants further investigation to clarify whether cocoa extract may help reduce AMD risk.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03205202.},
}

Humans
Female
Aged
Male
Double-Blind Method
*Dietary Supplements
*Macular Degeneration/prevention & control/epidemiology/diagnosis
Middle Aged
*Flavonols/administration & dosage
Risk Factors
Aged, 80 and over
*Cacao
*Plant Extracts/administration & dosage
Disease Progression
Follow-Up Studies
Incidence

@article {pmid40089134,
year = {2025},
author = {Gim, N and Ferguson, A and Blazes, M and Soundarajan, S and Gasimova, A and Jiang, Y and Sánchez, CI and Zalunardo, L and Corradetti, G and Elze, T and Honda, N and Waheed, NK and Cairns, AM and Canto-Soler, MV and Domalpally, A and Durbin, M and Ferrara, D and Hu, J and Nair, P and Lee, AY and Sadda, SR and Keenan, TDL and Patel, B and Lee, CS and , },
title = {Publicly available imaging datasets for age-related macular degeneration: Evaluation according to the Findable, Accessible, Interoperable, Reusable (FAIR) principles.},
journal = {Experimental eye research},
volume = {255},
number = {},
pages = {110342},
pmid = {40089134},
issn = {1096-0007},
support = {OT2 OD032644/OD/NIH HHS/United States ; P30 EY003790/EY/NEI NIH HHS/United States ; R01 AG060942/AG/NIA NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Tomography, Optical Coherence/methods ; *Databases, Factual ; Machine Learning ; Artificial Intelligence ; *Information Dissemination ; },
abstract = {Age-related macular degeneration (AMD), a leading cause of vision loss among older adults, affecting more than 200 million people worldwide. With no cure currently available and a rapidly increasing prevalence, emerging approaches such as artificial intelligence (AI) and machine learning (ML) hold promise for advancing the study of AMD. The effective utilization of AI and ML in AMD research is highly dependent on access to high-quality and reusable clinical data. The Findable, Accessible, Interoperable, Reusable (FAIR) principles, published in 2016, provide a framework for sharing data that is easily useable by both humans and machines. However, it is unclear how these principles are implemented with regards to ophthalmic imaging datasets for AMD research. We evaluated openly available AMD-related datasets containing optical coherence tomography (OCT) data against the FAIR principles. The assessment revealed that none of the datasets were fully compliant with FAIR principles. Specifically, compliance rates were 5 % for Findable, 82 % for Accessible, 73 % for Interoperable, and 0 % for Reusable. The low compliance rates can be attributed to the relatively recent emergence of these principles and the lack of established standards for data and metadata formatting in the AMD research community. This article presents our findings and offers guidelines for adopting FAIR practices to enhance data sharing in AMD research.},
}

Humans
*Macular Degeneration/diagnosis/diagnostic imaging
*Tomography, Optical Coherence/methods
*Databases, Factual
Machine Learning
Artificial Intelligence
*Information Dissemination

@article {pmid36535380,
year = {2024},
author = {Cao, J and Mongy, M and Ferreira, L and Brent, MH},
title = {Ganglion cell complex changes in wet AMD patients treated with anti-VEGF intravitreal injections according to a treat-and-extend protocol.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {59},
number = {2},
pages = {96-101},
doi = {10.1016/j.jcjo.2022.11.018},
pmid = {36535380},
issn = {1715-3360},
mesh = {Humans ; *Angiogenesis Inhibitors ; Vascular Endothelial Growth Factor A ; Intravitreal Injections ; Retrospective Studies ; Ranibizumab/therapeutic use ; *Wet Macular Degeneration/diagnosis/drug therapy ; Treatment Outcome ; Recombinant Fusion Proteins ; },
abstract = {OBJECTIVE: To analyze changes in ganglion cell complex (GCC) thickness in wet age-related macular degeneration (AMD) patients receiving intravitreal injections.

DESIGN: Retrospective cohort study involving 46 eyes at a single tertiary ophthalmology practice.

PARTICIPANTS: The injection group consisted of wet AMD patients who received intravitreal injections for at least 3 years following a treat-and-extend protocol. Twenty-two patients received ranibizumab, and 1 patient received aflibercept. The control group consisted of dry AMD patients who were observed only and did not receive medical treatment over the same period. GCC thickness and visual acuity were recorded at baseline and at 1-, 2-, and 3-year follow-up visits.

RESULTS: In the injection group, there was a nonsignificant trend toward reduction in GCC thickness over 3 years (-4.09 ± 8.47 µm; p = 0.09). Within the injection group, correlation analysis between the number of intravitreal injections and GCC thickness was nonsignificant but trended toward a direct relationship, with more injections correlated with a relatively thicker GCC at 3 years. There was no significant change in GCC thickness between baseline and year 3 for the control group.

CONCLUSIONS: Study results suggest that that there is no significant GCC thinning in wet AMD patients following a treat-and-extend regimen over 3 years.},
}

Humans
*Angiogenesis Inhibitors
Vascular Endothelial Growth Factor A
Intravitreal Injections
Retrospective Studies
Ranibizumab/therapeutic use
*Wet Macular Degeneration/diagnosis/drug therapy
Treatment Outcome
Recombinant Fusion Proteins

@article {pmid36320068,
year = {2022},
author = {Goncalves, A and Antonetti, DA},
title = {Transgenic animal models to explore and modulate the blood brain and blood retinal barriers of the CNS.},
journal = {Fluids and barriers of the CNS},
volume = {19},
number = {1},
pages = {86},
pmid = {36320068},
issn = {2045-8118},
support = {EY012021/NH/NIH HHS/United States ; HL055374/NH/NIH HHS/United States ; R01 EY012021/EY/NEI NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; R01 HL055374/HL/NHLBI NIH HHS/United States ; R01 EY029349/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Blood-Retinal Barrier/metabolism ; *Blood-Brain Barrier/metabolism ; Animals, Genetically Modified ; Endothelial Cells/physiology ; Central Nervous System ; },
abstract = {The unique environment of the brain and retina is tightly regulated by blood-brain barrier and the blood-retinal barrier, respectively, to ensure proper neuronal function. Endothelial cells within these tissues possess distinct properties that allow for controlled passage of solutes and fluids. Pericytes, glia cells and neurons signal to endothelial cells (ECs) to form and maintain the barriers and control blood flow, helping to create the neurovascular unit. This barrier is lost in a wide range of diseases affecting the central nervous system (CNS) and retina such as brain tumors, stroke, dementia, and in the eye, diabetic retinopathy, retinal vein occlusions and age-related macular degeneration to name prominent examples. Recent studies directly link barrier changes to promotion of disease pathology and degradation of neuronal function. Understanding how these barriers form and how to restore these barriers in disease provides an important point for therapeutic intervention. This review aims to describe the fundamentals of the blood-tissue barriers of the CNS and how the use of transgenic animal models led to our current understanding of the molecular framework of these barriers. The review also highlights examples of targeting barrier properties to protect neuronal function in disease states.},
}

Animals
*Blood-Retinal Barrier/metabolism
*Blood-Brain Barrier/metabolism
Animals, Genetically Modified
Endothelial Cells/physiology
Central Nervous System

@article {pmid35197297,
year = {2022},
author = {Palko, SI and Saba, NJ and Mullane, E and Nicholas, BD and Nagasaka, Y and Ambati, J and Gelfand, BD and Ishigami, A and Bargagna-Mohan, P and Mohan, R},
title = {Compartmentalized citrullination in Muller glial endfeet during retinal degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {119},
number = {9},
pages = {},
pmid = {35197297},
issn = {1091-6490},
support = {R21 EY028699/EY/NEI NIH HHS/United States ; R21 EY032741/EY/NEI NIH HHS/United States ; },
mesh = {Animals ; *Citrullination ; Gliosis/*metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neuroglia/*metabolism ; Retinal Degeneration/*metabolism ; Wet Macular Degeneration/metabolism ; },
abstract = {Muller glia (MG) play a central role in reactive gliosis, a stress response associated with rare and common retinal degenerative diseases, including age-related macular degeneration (AMD). The posttranslational modification citrullination targeting glial fibrillary acidic protein (GFAP) in MG was initially discovered in a panocular chemical injury model. Here, we report in the paradigms of retinal laser injury, a genetic model of spontaneous retinal degeneration (JR5558 mice) and human wet-AMD tissues that MG citrullination is broadly conserved. After laser injury, GFAP polymers that accumulate in reactive MG are citrullinated in MG endfeet and glial cell processes. The enzyme responsible for citrullination, peptidyl arginine deiminase-4 (PAD4), localizes to endfeet and associates with GFAP polymers. Glial cell-specific PAD4 deficiency attenuates retinal hypercitrullination in injured retinas, indicating PAD4 requirement for MG citrullination. In retinas of 1-mo-old JR5558 mice, hypercitrullinated GFAP and PAD4 accumulate in MG endfeet/cell processes in a lesion-specific manner. Finally, we show that human donor maculae from patients with wet-AMD also feature the canonical endfeet localization of hypercitrullinated GFAP. Thus, we propose that endfeet are a "citrullination bunker" that initiates and sustains citrullination in retinal degeneration.},
}

Animals
*Citrullination
Gliosis/*metabolism
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Neuroglia/*metabolism
Retinal Degeneration/*metabolism
Wet Macular Degeneration/metabolism

@article {pmid31927556,
year = {2020},
author = {Nasser, F and Kempf, M and Kurtenbach, A and Stöhr, H and Weber, BHF and Neuhaus, C and Rating, P and Zrenner, E},
title = {Correlating Adaptive Optics Images to Clinical Findings in Juvenile Macular Dystrophy with Hypotrichosis in Siblings with Homozygous CDH3 Pathogenic Variation.},
journal = {Ophthalmic research},
volume = {63},
number = {2},
pages = {141-151},
doi = {10.1159/000504757},
pmid = {31927556},
issn = {1423-0259},
mesh = {Adolescent ; Adult ; Cadherins/*genetics/metabolism ; DNA/*genetics ; DNA Mutational Analysis ; Electroretinography ; Female ; Humans ; Hypotrichosis/congenital/*diagnosis/metabolism ; Macular Degeneration/*diagnosis/genetics/physiopathology ; Male ; *Mutation ; Retinal Cone Photoreceptor Cells/*pathology ; Siblings ; Tomography, Optical Coherence ; *Visual Acuity ; },
abstract = {OBJECTIVE: We report on two German siblings diagnosed with congenital hypotrichosis and juvenile macular dystrophy, an extremely rare syndrome affecting both hair growth and visual functions.

METHODS: A detailed ophthalmological examination was carried out including fundus examination, visual acuity assessment, visual field determination, color vision testing, and electrophysiology (electroretinography [ERG]). Additionally, fundus photography and autofluorescence imaging (FAF) was performed, along with optical coherence tomography (OCT) and adaptive optics (AO) fundus imaging. Targeted Sanger sequencing and next-generation gene panel sequencing were carried out.

RESULTS: Macular dystrophy was evident in the fundus of both patients, as was a central scotoma in the static visual field. The kinetic visual field was normal. The ERG recordings were also normal, but the amplitudes of the multifocal ERG were reduced in the central 4-5° of the retina. The FAF images revealed a large central hypofluorescent area surrounded by a hyperfluorescent ring. The OCT images showed atrophy in the outer layers and tubulations. The AO images depicted a loss of central photoreceptors, as well as severe central atrophy in patient 1. A cone mosaic was observable in the peripheral AO fundus images of both patients. The disrupted cone mosaic on the AO images correlated with the hypofluorescent areas on autofluorescence. DNA testing identified the homozygous, likely pathogenic variant c.1508G>A/p.(Arg503His) (chr16:68719191) in the CDH3 gene.

CONCLUSIONS: The two siblings revealed hypotrichosis and macular dystrophy in both eyes. The identification of a homozygous CDH3 mutation in each patient confirms the syndromic entity of hypotrichosis with juvenile macular degeneration.},
}

Adolescent
Adult
Cadherins/*genetics/metabolism
DNA/*genetics
DNA Mutational Analysis
Electroretinography
Female
Humans
Hypotrichosis/congenital/*diagnosis/metabolism
Macular Degeneration/*diagnosis/genetics/physiopathology
Male
*Mutation
Retinal Cone Photoreceptor Cells/*pathology
Siblings
Tomography, Optical Coherence
*Visual Acuity

@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 Förderung der Wissenschaftlichen Forschung/ ; //Boehringer Ingelheim Pharma GmbH & 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.

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 weeks. The primary endpoint was the progression of GA area per eye. Potential correlations with clinical and imaging-based parameters were analysed.

RESULTS: The annual GA progression rate was 1.16 mm[2]/year (95% CI: 0.76-1.56; p < 0.001), with faster growth in eyes with larger baseline lesions (R[2] = 0.74). After square root transformation, the progression rate was 0.34 mm/year (95% CI: 0.26-0.43; p < 0.001), and the size dependency was reduced (adjusted R[2] = 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 = 0.017), the presence of perilesional hyperautofluorescence (p = 0.044) and a multifocal configuration of the GA lesions (p = 0.038). Intermediate AMD in the fellow eye was significantly associated with faster GA progression (p = 0.041).

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 {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 = {},
number = {},
pages = {},
doi = {10.1021/acs.jpcb.5c06621},
pmid = {41777091},
issn = {1520-5207},
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 {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 {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 {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.},
}

Humans
*Neural Networks, Computer
Algorithms
*Image Processing, Computer-Assisted/methods
*Retina/diagnostic imaging

@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 = {EY011373//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; EY018383//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; EY025383//U.S. Department of Health & 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.},
}

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

@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.},
}

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