@article {pmid42242290,
year = {2026},
author = {Al-Burak, SA and Suleiman, A and Voznyy, V and Elganga, M and Zajner, C and Juncal, V and Sheidow, TG and Malvankar-Mehta, MS},
title = {Age-related macular degeneration (AMD) associated with glucagon-like peptide-1 receptor agonist use: a systematic review.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2026.05.010},
pmid = {42242290},
issn = {1715-3360},
abstract = {BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly prescribed for diabetes, obesity, and cardiovascular risk reduction. However, their ocular safety profile, particularly regarding age-related macular degeneration (AMD), remains uncertain. This systematic review evaluates the association between GLP-1 RA use and the incidence or progression of AMD including both nonexudative and neovascular subtypes.

METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and registered with PROSPERO (CRD420251183938). MEDLINE, Embase, CENTRAL, Web of Science, and PubMed were searched from inception through 2025 for observational studies and randomized trials evaluating AMD outcomes among adults exposed to GLP-1 RAs. Comparators included nonuse, placebo, or alternative metabolic therapies. Risk of bias was assessed using Risk of Bias in Non-Randomized Studies of Interventions and certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. Due to heterogeneity of outcome definitions, results were synthesized qualitatively.

RESULTS: Eight observational studies encompassing 91 408 to 600 816 participants were included. GLP-1 RA use was associated with a reduced incidence of nonexudative AMD across diabetic and nondiabetic populations, with relative risk reductions varying substantially by population, comparator, and follow-up duration. Findings for neovascular AMD were heterogeneous: most studies reported neutral or protective associations, whereas one population-based cohort of older adults with diabetes observed an increased risk (adjusted hazard ratio 2.21, 95% CI 1.65-2.96), with low absolute event rates. Overall risk of bias was moderate to high, and certainty of evidence for all outcomes was very low.

CONCLUSIONS: Current evidence does not demonstrate a consistent increase in AMD risk associated with GLP-1 RA therapy and may be associated with a lower incidence of nonexudative AMD, although the certainty of evidence is very low and noncausal explanations cannot be excluded. Prospective studies with standardized endpoints are needed to clarify causal relationships.},
}

@article {pmid42242606,
year = {2026},
author = {Boyer, DS and Saad, L and Washington, I and Melamud, A and Graham, KB and O'Malley, AE and DeBartolomeo, GM and Jiang, H and Harris, LD and Kay, CN and Ferrone, PJ and Khan, S and , },
title = {Gildeuretinol Acetate vs Placebo for Geographic Atrophy Secondary to Age-Related Macular Degeneration: The SAGA Randomized Clinical Trial.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.05.018},
pmid = {42242606},
issn = {2468-6530},
abstract = {OBJECTIVE: To assess the effects of gildeuretinol acetate (C20D3-vitamin A) in geographic atrophy (GA).

DESIGN: 24-month, double-masked, multicenter, randomized, placebo-controlled trial.

PARTICIPANTS: Participants ≥60 years with GA.

INTERVENTIONS: Randomized 2:1 to oral gildeuretinol acetate 14 mg daily or placebo.

MAIN OUTCOME MEASURES: The primary endpoint was GA growth rate from baseline to 24 months. A prespecified sensitivity analysis accounted for a 6-month delay in onset of therapeutic effect. Secondary endpoints included change from baseline in low luminance visual acuity (LLVA), best-corrected visual acuity (BCVA), Visual Function Questionnaire (VFQ)-25, and Functional Reading Independence (FRI) Index.

RESULTS: Among 198 randomized participants (mean [SD] age 78.4 [7.0] years; 68.7% female), 69.2% completed the 24-month study. In the gildeuretinol and placebo groups, baseline mean (SD) total GA lesion area in mm[2] was 7.72 (6.10) and 7.09 (4.16); BCVA letter scores were 56.2 (21.3) (Snellen equivalent: ∼20/80) and 58.8 (18.0) (∼20/70); and LLVA letter scores were 31.1 (19.0) (∼20/200) and 31.6 (17.8) (∼20/250), respectively. Mean GA growth rates were 1.62 mm[2]/year with gildeuretinol and 1.87 mm[2]/year with placebo (least squares [LS] mean difference: -0.25 mm[2]/year; 95% CI: -0.53, 0.03; P = 0.075), a 13.4% relative reduction for gildeuretinol vs placebo. The LS mean (SE) GA growth rates from 6 to 24 months were 1.90 (0.12) mm[2]/year (placebo) and 1.61 (0.08) mm[2]/year (gildeuretinol), a 15.3% relative reduction (-0.29 mm[2]/year; 95% CI: -0.576, -0.004; nominal P = 0.047). At 24 months, LLVA declined 3.9 and 8.3 ETDRS letters in the gildeuretinol and placebo groups, respectively (difference: 4.4 letters; 95% CI: 0.40, 8.41; nominal P = 0.031). BCVA declined 6.9 letters with gildeuretinol and 10.2 letters with placebo (difference: 3.3 letters; 95% CI: -0.63, 7.23; P = 0.099). VFQ-25 scores declined 4.81 fewer points with gildeuretinol than placebo (95% CI: 0.87, 8.76; nominal P = 0.017) and FRI scores declined 0.35 fewer points (95% CI: 0.11, 0.58; nominal P = 0.004).

CONCLUSIONS: The prespecified primary endpoint was not met. Prespecified piecewise and secondary functional/patient-reported analyses favored gildeuretinol with nominal P values; these exploratory findings support further evaluation in adequately powered trials.},
}

@article {pmid42243112,
year = {2026},
author = {Cui, X and Hui, J and Zhao, Q and Han, Q},
title = {Plant-based diet quality and risk of age-related eye diseases: evidence from multi-cohorts with multi-omics insights.},
journal = {NPJ science of food},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41538-026-00919-z},
pmid = {42243112},
issn = {2396-8370},
support = {NKSGZ202305//Nankai University Eye Institute Key Science and Technology Fund/ ; TJYXZDXK-3-004A-3//Tianjin Key Medical Discipline Construction/ ; },
abstract = {Plant-based diets may influence age-related eye diseases (AREDs), but whether ocular benefits depend on diet quality remains unclear. We examined associations of a healthy plant-based diet index (PDI-H) and an unhealthy plant-based diet index (PDI-U) with age-related macular degeneration (AMD), cataract, glaucoma, diabetic retinopathy (DR), and retinal vein occlusion (RVO) using the UK Biobank prospective cohort and an independent Tianjin hospital-based cross-sectional sample. Cox regression, logistic regression, propensity score matching, restricted cubic splines, subgroup analyses, multi-omics profiling, and machine learning were applied. Higher PDI-H was associated with lower risks of AMD, cataract, glaucoma, and DR, whereas higher PDI-U was associated with increased risks of AMD, cataract, and DR. Associations with RVO were weak or absent. Findings from Tianjin were directionally consistent with UK Biobank results and should be interpreted as supportive cross-sectional evidence. Proteomic and metabolomic analyses linked plant-based diet quality to inflammation, lipid metabolism, glycaemic regulation, and hormonal signalling. Predictive models incorporating dietary indices showed good discrimination for AMD and cataract, with modest but consistent AUC improvements after adding PDI-H and PDI-U to traditional risk factors. These findings suggest that plant-based diet quality, rather than plant-based eating alone, may be a modifiable determinant of major AREDs.},
}

@article {pmid42243270,
year = {2026},
author = {Pawloff, M and Linhardt, D and Woletz, M and Hollaus, M and Mylonas, G and Holder, GE and Sacu, S and Windischberger, C and Ritter, M},
title = {Robust and reproducible population receptive field mapping in patients with retinal pathologies.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42243270},
issn = {1476-5454},
support = {KLI 670-B30; P35583//Austrian Science Fund (Fonds zur Förderung der Wissenschaftlichen Forschung)/ ; },
abstract = {PURPOSE: Previous studies have shown high reproducibility of population receptive field (pRF) mapping in young, healthy individuals. The present study examines whether such a level of reproducibility can also be achieved in patients suffering from retinal disease.

METHODS: Eleven patients with Stargardt disease and eleven patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) were examined in up to four sessions using high-resolution ultra-high field fMRI (Siemens Magnetom 7 T) and microperimetry (MP, Nidek MP-3). Reproducibility of the pRF parameters within and between sessions was assessed using Spearman's correlation coefficient.

RESULTS: Retinotopic maps calculated from ultra-high field MRI had excellent intra- and intersession reproducibility for pRF center position (median correlation between sessions for pRF center eccentricity: r = 0.91; polar angle: r = 0.90), but only modest reproducibility for pRF size (average correlation r = 0.39). Reproducibility was constant across sessions multiple weeks apart, indicating a long-term stability of the method. In addition, the results show that reproducibility is not related to the severity of retinal disease.

CONCLUSION: The data demonstrate that retinotopic mapping of the primary visual cortex using ultra-high field MRI is a highly reproducible technique for the assessment of macular function in patients with retinal disease. The technique provides an unbiased quantification of retinal function adjunct to conventional clinical assessments and may assist the early diagnosis of retinal disease. In addition, it may be a valuable objective method for monitoring visual deficits during long-term therapeutic interventions or disease progression.},
}

@article {pmid42245065,
year = {2026},
author = {Lee, SS and Wang, CA and de Vries, VA and van Hemert, DJ and Schulze, A and Brandl, C and Aman, AM and Alonso-Caneiro, D and Choquet, H and Gorski, M and Hammond, CJ and Heid, IM and Hunter, ML and Hysi, P and Jiang, C and Jonas, J and Klaver, CC and Kneepkens, SC and Konig, S and Lingham, G and Luber, C and Melton, PE and Pennell, CE and Ramdas, WD and Read, SA and Schuster, AK and Wang, YX and Zimmermann, ME and , and Khawaja, AP and Gharahkhani, P and MacGregor, S and Guggenheim, JA and Mackey, DA},
title = {Genome-wide discovery reveals 30 loci for choroidal thickness and uncovers potential causal links with angle-closure glaucoma.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.26.26354075},
pmid = {42245065},
abstract = {The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.},
}

@article {pmid42232161,
year = {2026},
author = {Guo, H and Yan, R and Han, X and Yu, W},
title = {Dysregulated Polarized Secretion of Small Extracellular Vesicles in the Retinal Pigment Epithelium: Mechanisms and Pathological Roles in Age-Related Macular Degeneration.},
journal = {Journal of inflammation research},
volume = {19},
number = {},
pages = {612984},
pmid = {42232161},
issn = {1178-7031},
abstract = {The pathogenesis of age-related macular degeneration (AMD) is intrinsically driven by retinal pigment epithelium (RPE) dysfunction. Under physiological conditions, the strictly polarized secretion of small extracellular vesicles (sEVs) by the RPE dictates outer retinal homeostasis. In response to oxidative and hypoxic stress, this secretory architecture is profoundly disrupted, transforming sEVs into mediators of drusen formation, inflammation, and neovascularization. This review systematically delineates the molecular machinery governing RPE-sEV trafficking, unveiling the distinct protein and miRNA cargo profiles segregated between the apical and basolateral domains. We highlight the unique secretory features of RPE and elucidate how AMD stressors disrupt this polarity via cytoskeletal collapse, secretory autophagy, and Rab GTPase dysregulation. Consequently, this altered sEV secretion abolishes apical neurotrophic support while deteriorating the basolateral microenvironment. Crucially, this establishes a vicious pathological loop where microenvironmental deterioration and sEV dysregulation are mutually causative. Recognizing dysregulated sEV polarity as a contributing factor to AMD, we propose that repairing RPE intracellular trafficking offers a fundamental strategy to restore secretory homeostasis and impede disease progression.},
}

@article {pmid42233695,
year = {2026},
author = {Battu, P and Sharma, S and Singh, R and Anand, A},
title = {Circulating biomarker profile and its diagnostic predictive utility in age-related macular degeneration.},
journal = {Biomarkers in medicine},
volume = {},
number = {},
pages = {1-10},
doi = {10.1080/17520363.2026.2677199},
pmid = {42233695},
issn = {1752-0371},
abstract = {PURPOSE: We evaluated the serum expression profiles of proteins encoded by AMD-related genes in age-related macular degeneration patients and controls.

METHODS: In our case-control study, we employed Enzyme-linked immunosorbent assay (ELISA) to analyze the expression of Collagen type X alpha 1 chain (COL10A1), Transforming growth factor-beta receptor type 1(TGFβR1) and Tumor Necrosis Factor Receptor Superfamily (TNFRSF10A) in serum. We have also statistically analyzed the correlations among the biomarkers and further assessed their diagnostic potential using the least absolute shrinkage and selection operator (LASSO) regression.

RESULTS: Out of three evaluated serum protein levels, two were found to be significantly associated with AMD. The expression of COL10A1 was significantly upregulated (p < 0.0001), and TNFRSF10A was significantly downregulated (p < 0.0001) in AMD patients compared to controls. The LASSO logistic regression revealed that serum expression of COL10A1 and TNFRSF10A proteins can reliably differentiate AMD cases from controls with predictive accuracy of 87.3%.

CONCLUSION: Our findings indicate that serum levels of COL10A1 and TNFRSF10A are significantly altered in AMD patients compared to controls. LASSO regression analyses further revealed that these proteins together have a strong ability to differentiate between AMD cases and controls, suggesting their potential as reliable biomarkers for risk prediction of AMD.},
}

@article {pmid42234083,
year = {2026},
author = {Saraf, A and Garima, K and Dharwadkar, S and Keshav, S and Patwardhan, SD and Giri, NB and Saxena, M and Phadke, Y and Khare, A and Mishra, A and Kumar, V and Singh, S},
title = {Safety of GBL1204-An Ophthalmic Bevacizumab in Prefilled Syringe for Neovascular Age-Related Macular Degeneration: A Phase I Study.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42234083},
issn = {2193-8245},
abstract = {INTRODUCTION: GBL1204 1.25 mg is an ophthalmic-grade bevacizumab formulation, manufactured in accordance with the stringent ophthalmic quality standards, and supplied in a single-use prefilled syringe (PFS). This clinical trial evaluated the short-term safety and biological activity of a single intravitreal injection of ophthalmic bevacizumab in patients with neovascular age-related macular degeneration (nAMD).

METHODS: This phase I, open-label, single-arm, multicentre trial enrolled 16 participants (aged ≥ 50 years) with best-corrected visual acuity (BCVA) score using Early Treatment of Diabetic Retinopathy Study charts of 20/40-20/320 (approximate Snellen equivalent) at five centres across India. Participants were administered a single intravitreal injection of GBL1204 (1.25 mg/0.05 mL). The main objective was evaluation of ocular and systemic treatment-emergent adverse events (TEAEs), and laboratory parameters over 4 weeks.

RESULTS: GBL1204 complies with the particulate matter standards specified in the United States Pharmacopeia USP < 789 > for ophthalmic injectable solutions. GBL1204 was safe and well tolerated by the patients over 4 weeks. No ocular or systemic serious adverse events occurred. Nine participants (56.25%) reported 14 TEAEs (13 ocular, 1 non-ocular). Of the 14 adverse events, 8 (57.14%) were considered as mild; all adverse events resolved on their own, and without any sequelae. Mean (standard error mean, SEM) BCVA improvement from baseline was + 1.80 (0.76) letters at day 7 and + 3.0 (1.10) letters at day 28. The corresponding mean (SEM) central macular thickness reductions were - 41.67 µm (40.35) and - 64.67 µm (42.74) at days 7 and 28, respectively. Serum vascular endothelial growth factor levels showed expected suppression consistent with bevacizumab pharmacodynamics.

CONCLUSION: A single intravitreal injection of GBL1204 demonstrated favourable short-term safety and tolerability, with evidence of visual and anatomical improvements. These findings support further evaluation of GBL1204 1.25 mg PFS in a pivotal phase III trial as a standardized alternative to compounded bevacizumab. Trial Registration Clinical Trial Registry-India (CTRI): Identification no. CTRI/2024/02/063012.},
}

@article {pmid42236129,
year = {2026},
author = {Zhang, C and Sonik, NR and Ayoubi, M and AbouKasm, G and Zhu, D and Fan, JC and Albini, TA and Yannuzzi, NA},
title = {Clinical efficacy and safety of aflibercept biosimilars in neovascular age-related macular degeneration: a systematic review and meta-analysis of randomised controlled trials.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328196},
pmid = {42236129},
issn = {1468-2079},
abstract = {BACKGROUND: To evaluate the efficacy and safety of aflibercept biosimilars compared with reference aflibercept in the treatment of neovascular age-related macular degeneration (nAMD).

METHODS: A systematic review and meta-analysis were conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered on PROSPERO (CRD4201069147). Phase 3 randomised controlled trials (RCTs) comparing aflibercept biosimilars to reference aflibercept in treatment-naïve nAMD were included. All included studies employed a standardised on-label aflibercept dosing regimen consisting of three initial monthly loading doses followed by injections every 8 weeks. The primary outcome was the mean difference (MD) in best-corrected visual acuity (BCVA) at week 8. Secondary outcomes included BCVA at week 52, proportion of patients gaining ≥15 letters or maintaining vision (<15-letter loss), central subfield thickness (CST) and adverse events (AEs).

RESULTS: Six RCTs (2022-2024) were included, comprising 2029 eyes (1020 biosimilar; 1009 reference). BCVA at week 8 did not differ significantly between groups (MD -0.34 letters; 95% CI -1.12 to 0.44; I²=0%; p=0.39), as was BCVA at week 52 (MD -0.04; 95% CI -1.18 to 1.10; I²=1%; p=0.94). No differences were observed in the proportion of patients gaining ≥15 letters, maintaining vision, CST changes or AEs.

CONCLUSIONS: Aflibercept biosimilars demonstrated no significant difference in efficacy at 8 weeks and 52 weeks as well as safety relative to reference aflibercept in eyes with treatment-naïve nAMD following an on-label aflibercept treatment protocol; however, real-world extended durability remains untested. These findings were supported by a low risk of bias and a high-certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations tool.},
}

@article {pmid42237272,
year = {2026},
author = {Kong, M and Jin, R and Cheng, T and Sun, L and Tong, N},
title = {Serum microRNA-34a as a circulating biomarker for age-related macular degeneration and short-term anti-VEGF response in neovascular AMD.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04983-7},
pmid = {42237272},
issn = {1471-2415},
abstract = {OBJECTIVE: To evaluate whether serum microRNA-34a (miR-34a) is associated with age-related macular degeneration (AMD) and whether baseline serum miR-34a has the potential to predict short-term response to anti-vascular endothelial growth factor (anti-VEGF) therapy in patients with neovascular AMD (nAMD).

METHODS: In a cross-sectional cohort recruited at Qingdao Municipal Hospital between January and December 2024, serum miR-34a was quantified in 160 AMD patients and 122 age- and sex-matched healthy controls. AMD was staged according to Age-related Eye Disease Study (AREDS) criteria. Patients with nAMD received three consecutive monthly intravitreal anti-VEGF injections during the loading phase and were classified as good or poor responders according to prespecified anatomical and functional criteria based on optical coherence tomography (OCT) and best-corrected visual acuity (BCVA) after the loading phase. Peripheral blood samples were collected, and serum miR-34a expression was quantified using standard qPCR protocols.

RESULTS: Serum miR-34a was significantly higher in patients with AMD than in controls (p < 0.001). Receiver operating characteristic (ROC) analysis yielded an area under the curve (AUC) of 0.740 (95% CI 0.681-0.799; p < 0.0001) for discriminating AMD from controls. Across AMD subgroups, serum miR-34a differed significantly overall; patients with geographic atrophy (GA) exhibited higher miR-34a levels than those with nAMD (p < 0.05). Among patients with nAMD, baseline serum miR-34a was remarkably higher in good responders than in poor responders after the loading phase (p < 0.001). ROC analysis showed an AUC of 0.772 (95% CI 0.687-0.857; p < 0.0001) for predicting treatment response, and multivariable logistic regression identified higher serum miR-34a as independently associated with lower odds of poor response (OR 0.143, 95% CI 0.042-0.489; p = 0.002).

CONCLUSION: Elevated serum miR-34a is associated with AMD and may serve as a minimally invasive biomarker for distinguishing AMD from controls. In nAMD, baseline serum miR-34a also showed potential for predicting short-term response to loading-phase anti-VEGF therapy. These findings warrant validation in larger, longitudinal, and preferably multicenter cohorts.},
}

@article {pmid42239431,
year = {2026},
author = {Diwedi, B and Neog, A and Baanannou, A and Das, P and Menard, R and Halluin, C and Morse, D and Emmerich, K and Thierer, JH and Patnaude, M and Bonnet, F and Graber, JH and Mumm, JS and Madelaine, R},
title = {Mesenchymal-derived neural progenitors underlie local insulin production and neuronal transdifferentiation during retina regeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.05.20.726251},
pmid = {42239431},
issn = {2692-8205},
abstract = {In humans, retinal-neuron death, optic-nerve injuries, and associated neurodegenerative diseases, such as glaucoma and age-related macular degeneration, often lead to permanent vision loss. While the capacity for regeneration is low in the human nervous system, including the retina, some non-mammalian vertebrate species, including zebrafish, are capable of endogenous neuronal regeneration after injury. Unlike mammals, zebrafish do not form a scar that inhibits axonal and neuronal regeneration after injury. Rather, they harbor neural progenitor and stem-cell populations allowing regeneration of entire parts of the nervous system and restoration of tissue integrity and function. In the zebrafish retina, cycling neural progenitor cells of the ciliary marginal zone and quiescent resident neural stem cells (the latter of which are also called Müller glial cells) participate in neuronal regeneration following different types of injury. In this study, we report the identification of a novel, additional cellular source participating in neuronal regeneration of neurons in the zebrafish retina after genetic ablation of retinal ganglion cells. Before injury, these progenitor cells express molecular markers of neural-crest-cell and/or fibroblast identity, such as sox10 , pdgfrb , and eya2 , while after neuronal ablation they also express proneural factors including the ascl1a and olig2 genes. Combining genetic ablation of neurons with photoconversion or Cre/Lox-dependent genetic lineage tracing of sox10 -expressing cells, we demonstrated that these cells can differentiate into post-mitotic retinal neurons in the ganglion cell layer (GCL) in the absence of cell proliferation. We also showed, surprisingly, that this progenitor population locally produces insulin mRNA, and that insulin signaling is involved in the accumulation of mesenchymal-derived neural progenitors in the GCL and in their subsequent transdifferentiation into RGCs. This work reveals an unexpected and novel cellular mechanism of transdifferentiation, dependent on a neural-crest-derived mesenchymal cell population, participating in neuronal regeneration in the zebrafish retina. The discovery of this plastic cell population could potentially lead to new strategies to promote the formation of new neurons in the mammalian retina.},
}

@article {pmid42239615,
year = {2026},
author = {Wang, J and Wang, Q},
title = {IMPG1 Variant Causing Adult-Onset Foveomacular Vitelliform Dystrophy in Chinese: A Case Report.},
journal = {Case reports in ophthalmology},
volume = {17},
number = {1},
pages = {448-454},
pmid = {42239615},
issn = {1663-2699},
abstract = {INTRODUCTION: Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare entity and is mostly reported in French individuals. Here, we report a Chinese patient with AOFVD who had IMPG1 mutation and was misdiagnosed with age-related macular degeneration (AMD).

CASE PRESENTATION: A 59-year-old man complaining of vision loss was misdiagnosed with AMD and treated with intravitreal injections of anti-vascular endothelial growth factor, but with no improvement. Visual acuity was 20/50 in the right eye and 20/40 in the left eye. Fundus examinations revealed a bilateral symmetrical vitelliform "egg yolk" lesion. Spectral-domain optical coherence tomography revealed dome-shaped subretinal hyperreflective materials and cuticular drusen at the retinal pigment epithelium-Bruch's membrane complex in both eyes. No clear neovascularization was observed. Electrooculography revealed a decreased Arden ratio. Based on multimodal imaging analysis and genetic testing, the patient was diagnosed with AOFVD. No therapeutic intervention was administered. One month after the patient's visit, vitelliform "egg yolk" lesion was absorbed in the right eye, and the patient's visual acuity decreased to 20/100 in the right eye.

CONCLUSION: AOFVD is rare and underdiagnosed. It can disguise as AMD or other similar macular diseases. Clinicians should be alert to this condition, pay attention to its identification, and avoid unnecessary treatments.},
}

@article {pmid42240907,
year = {2026},
author = {Güçlü, H and Doğanlar, Z and Şambel Aykutlu, M and Köse, G and Doğanlar, O},
title = {The role of STAT3-targeted therapy created with COLIVELIN in the cross-talk between IL6/JAK2/STAT3 and TGF-β/SMAD2/SMAD3 signaling in a hyperinflammation and ROS-induced in vitro AMD model and its effect on retinal apoptosis.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42240907},
issn = {1573-2630},
support = {(TÜBAP-2021/68)//Republic of Türkiye Trakya University Scientific Research Projects Unit/ ; },
abstract = {This study aimed to investigate the therapeutic potential of Colivelin in modulating the cross-talk between the IL-6/JAK2/STAT3 and TGF-β/SMAD2/SMAD3 signaling pathways and its downstream effects on retinal apoptosis in an in vitro AMD model. An in vitro AMD model was established in ARPE-19 human RPE cells using a sublethal combination of lipopolysaccharide and hydrogen peroxide. Apoptosis was quantified via Tali® image cytometry. Gene expression profiling was performed by qRT- PCR. Protein expressions were assessed by Western blot. Formal mediation analysis was employed to quantify pathway-specific mechanistic contributions. The AMD model exhibited significant upregulation of hypoxia-related genes (HIF-1α, VEGF, MMP3, MMP9), pro-inflammatory cytokines (IL-6, TNF-α), and pro-apoptotic markers (BAX, p53, Caspase- 3), accompanied by markedly elevated ROS levels and reduced cell viability. Low-dose Colivelin (1 µM) significantly enhanced STAT3 phosphorylation, restored antioxidant gene expression (GSS, CAT, SOD2), suppressed hypoxia-associated gene expression, and substantially reduced TGF-β receptor, SMAD2, and SMAD3 expression at both transcriptional and protein levels. Formal mediation analysis revealed that 91-98% of Colivelin's anti-apoptotic effect at the therapeutic dose was mediated through STAT3-driven suppression of TGF-β/SMAD2/3 signaling, rather than through direct STAT3 transcriptional activity on apoptotic target genes. Conversely, high-dose Colivelin (10 µM) paradoxically activated SMAD2/3-independent pro-apoptotic cascades, demonstrating a dose- dependent biphasic response. This study provides the first formal mechanistic evidence that Colivelin exerts its cytoprotective effects in AMD primarily through a STAT3 → SMAD2/3 suppression axis. Low-dose (1 µM) Colivelin demonstrated superior and broader therapeutic efficacy compared to Bevacizumab by simultaneously modulating oxidative stress, hypoxia, angiogenesis, and apoptotic signaling pathways. These findings establish Colivelin as a promising multi-target therapeutic candidate for AMD, with its therapeutic window defined by the capacity of STAT3 activation to selectively suppress TGF-β/SMAD-driven apoptotic signaling without engaging compensatory pro-death mechanisms. Rigorous pharmacokinetic optimization and in vivo validation are warranted to advance Colivelin toward clinical translation.},
}

@article {pmid42240995,
year = {2026},
author = {Xue, CC and Chee, ML and Li, H and Tham, YC and Cheng, CY},
title = {Reported Metformin Use and Age-Related Macular Degeneration in Patients With Diabetes.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.1799},
pmid = {42240995},
issn = {2168-6173},
}

@article {pmid42230733,
year = {2026},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX},
title = {Presence and associations of retinal pigment epithelium and outer retinal atrophy: the Beijing eye study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-55175-8},
pmid = {42230733},
issn = {2045-2322},
abstract = {The goal of the study was to assess the presence of an incomplete (iRORA) and complete (cRORA) retinal pigment epithelium (RPE) and outer retinal atrophy in a general population and explore their associations with other parameters. Participants of the population-based Beijing Eye Study with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV) or those without retinal diseases, underwent optical coherence tomography of the macula. Among 5894 eyes, presence of iRORA and cRORA increased from 0/5117 (0%) and 0/5117 (0%) in the normal group and 0/457 (0%) and 0/457 (0%) in early AMD to 5/277 (1.8%;95%CI:0.3,3.3) and 0/277 (0%) in intermediate AMD, 6/6 (100%) and 6/6 (100%) in geographic atrophy, 0/2 (0%) and 2/2 (100%) in exudative AMD, and 10/30 (33.3%;95%CI:17.8,48.8) and 6/30 (25.0%;95%CI:12.0,38.0) in PCV, respectively. Higher iRORA presence was associated (multivariable analysis) with higher AMD stage (OR:54.7;95%CI:6.68,449;P < 0.001), higher PCV presence (OR:1.523 × 10[5];95%CI:834,2.785 × 10[7];P < 0.001), and higher presence of reticular pseudodrusen (OR:19.2;95%CI:1.94,190;P < 0.001). Drusen number (OR:0.97;95%CI:0.91,1.03;P = 0.27) and subfoveal choroidal thickness (OR:1.003;95%CI:0.994,1.013;P = 0.49) were not associated. Higher cRORA presence correlated with higher PCV presence (OR:48.6;95%CI:4.58,517;P = 0.001) and higher presence of reticular pseudodrusen (OR:120;95%CI:13.1,1094;P < 0.001). iRORAs and cRORAs were spatially associated with ellipsoid zone and external limiting membrane defects and intraretinal hyperreflective foci (iHRFs) in the outer and inner retinal layers. The findings suggest that iRORAs and cRORAs presences were relatively low in our population-based study, and were associated with higher presence of reticular pseudodrusen but not with drusen number or subfoveal choroidal thickness. The spatial association with ellipsoid zone defects and external limiting membrane defects and iHRF in the outer retinal layer and beyond fits with the notion of an RPE cell migration playing a role in the development of iRORAs and cRORAs.},
}

@article {pmid42230802,
year = {2026},
author = {Swaroop, A and Roska, B},
title = {Revisiting retinal and macular degeneration in the genomics era.},
journal = {Nature reviews. Genetics},
volume = {},
number = {},
pages = {},
pmid = {42230802},
issn = {1471-0064},
abstract = {Retinal and macular degeneration constitute a prominent cause of untreatable vision loss globally. The development of efficacious therapies is impeded by extensive clinical and genetic heterogeneity, poor phenotype-genotype correlation and lack of appropriate disease models. Pioneering advances in next-generation sequencing together with computational methods, human model systems and genetic manipulation technologies have begun to unravel causal genes and variants as well as gene interaction networks. Photoreceptor dysfunction or death represents the end point for both Mendelian and complex traits affecting the retina or its specialized central region, the macula. Here we review the genetic and genomic bases of retinal and macular degeneration and how recent advances are informing therapies to slow the loss of or restore vision.},
}

@article {pmid42230852,
year = {2026},
author = {Wu, X and Zhang, X and Jiang, Y and Gu, Z and Li, C and Zhu, X and Huang, Y and Li, B and Ma, M and Zhao, S and Zheng, Z},
title = {Association of high-intensity evening light exposure with risk of incident age-related macular degeneration, cataract, and glaucoma: a prospective cohort study of 82,826 participants.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42230852},
issn = {2509-2723},
abstract = {Excessive artificial light at night (ALAN) disrupts circadian rhythms and may accelerate ocular aging; however, personal objective dosimetry data linking evening light exposure to specific age-related eye diseases (AREDs) remain sparse. The objective of the study is to determine whether personal high-intensity light exposure during the evening transition window (20:00-23:30) is associated with the risk of incident age-related macular degeneration (AMD), cataracts, and glaucoma. This prospective cohort study utilized data from the UK Biobank. Participants (n = 82,826) were monitored for 7 days via wrist-worn accelerometers equipped with high-resolution light sensors between 2013 and 2015. Individuals with baseline eye diseases were excluded. Average light intensity (lux) during the evening transition period (20:00-23:30) was categorized by percentiles (top 10% threshold ≈1000 lx). Incident AMD, cataract, and glaucoma were identified through linked hospital inpatient records and death registries using ICD-9 and ICD-10 codes. Among 82,826 participants, 6058 incident ARED cases occurred during a median follow-up of 7.85 years. Evening light exposure exceeding 1000 lx (top 10%) was significantly associated with increased hazards of incident AMD (HR, 1.31; 95% CI, 1.06-1.62), cataract (HR, 1.18; 95% CI, 1.08-1.30), and primary open-angle glaucoma (POAG) (HR, 1.47; 95% CI, 1.07-2.03). Significant time-response relationships were observed, with per-hour exposure to > 2250 lx further elevating the risk of overall AREDs (HR, 1.10; 95% CI, 1.04-1.16) and POAG (HR, 1.18; 95% CI, 1.04-1.35). High-intensity artificial light in the evening is an independent, modifiable risk factor for major ocular aging pathologies.},
}

@article {pmid42223803,
year = {2026},
author = {Servin, AE and McFadden, I and Esmaeilkhanian, H and Holcomb, D and Lin, J and Awh, CC},
title = {Real-World Utilization and Initial Experience with Aflibercept-ayyh (PAVBLU[®]) for Retinal Disorders in United States Retina Practices: A Descriptive Retrospective Analysis.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42223803},
issn = {2193-8245},
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) therapies are standards of care for vision-threatening retinal diseases. This retrospective observational study describes demographics, utilization, best recorded visual acuity (BRVA), and safety among eyes with neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), diabetic macular edema (DME), or retinal vein occlusion (RVO) treated with the biosimilar aflibercept-ayyh (PAVBLU[®]) in routine clinical practice.

METHODS: Electronic medical records from the Retina Consultants of America database of patients receiving aflibercept-ayyh (12/1/2024-10/31/2025) were analyzed, focusing on eyes with ≥ 84 days of follow-up. The index date was defined as the first documented aflibercept-ayyh injection. Post-index data were used to evaluate treatment patterns, changes in BRVA, and adverse events of special interest (AESIs). Within-eye changes in BRVA were assessed using the Wilcoxon signed rank test and summarized as mean change in logarithm of the minimum angle of resolution (ΔlogMAR).

RESULTS: A total of 1000 consecutive eyes from 989 patients (55% female, 43% male, 2% unknown) received 3730 injections of aflibercept-ayyh; 91% switched from prior anti-VEGF therapy and 9% were anti-VEGF treatment-naïve. Disease distribution was 58% nAMD, 19% RVO, 16% DME, and 7% DR. Among switchers, median (IQR) number of prior injections was 21 (8, 46). Median (IQR) follow-up was 6.0 months (4.6, 7.1). Median (IQR) number of aflibercept-ayyh injections per eye was 4 (3, 5). Among eyes with ≥ 84 days of follow-up (n = 889), mean BRVA logMAR remained stable for switchers (0.4 to 0.4; P = 0.96) and improved from baseline in anti-VEGF-naïve eyes (0.5 to 0.4; P < 0.01). Confirmed AESIs included iritis (n = 2; 0.05% of injections), with no events of vitreous cells, endophthalmitis, retinal detachment, retinal vasculitis, or vitreous hemorrhage.

CONCLUSION: In this descriptive real-world analysis, aflibercept-ayyh was associated with stable visual acuity in previously treated eyes and vision improvement in treatment-naïve eyes, with no new or unexpected safety findings, consistent with expectations for aflibercept and the established body of evidence supporting biosimilarity between aflibercept-ayyh and reference aflibercept, EYLEA[®]).},
}

@article {pmid42224684,
year = {2026},
author = {Nadar, D and Shende, P},
title = {Unveiling the Potential of Drug Delivery Systems for Tyrosine Kinase Inhibitors in the Treatment of Neovascular Eye Diseases.},
journal = {Critical reviews in therapeutic drug carrier systems},
volume = {43},
number = {2},
pages = {61-123},
doi = {10.1615/CritRevTherDrugCarrierSyst.2026060256},
pmid = {42224684},
issn = {2162-660X},
abstract = {Tyrosine kinase inhibitors (TKIs) represent a promising category of therapeutic agents for managing edema and neovascular eye diseases (NEDs) such as corneal neovascularization, proliferative diabetic retinopathy and neovascular age-related macular degeneration. By impeding the phosphorylation of receptor tyrosine kinases, TKIs prevent the activation of angiogenic signaling pathways that are vital for cell growth and proliferation. However, the TKIs delivery in ophthalmology presents significant challenges such as toxicity and poor bioavailability. This review discusses emerging TKIs for NEDs, their physicochemical properties, and delivery systems, highlighting strategies such as sustained-release ocular implants, hydrogels, particulate and composite systems. Amid each category, we explore groundbreaking research approaches with a focus on preclinical and clinical studies, providing an in-depth look at the latest advancements in TKI-based delivery systems. Numerous TKI formulations currently under investigation (AXPAXLI, DURAVYU, CLS-AX and D-4517.2) hold the potential to improve therapeutic outcomes and enhance patient adherence, transforming the treatment landscape of NEDs. Advanced TKI delivery platforms, integrated with artificial intelligence-driven tools and minimally invasive technologies may enable more effective and personalized treatment options in the field of eye care.},
}

@article {pmid42225822,
year = {2026},
author = {Sun, H and Bu, F and Xin, X and Yan, J and Huang, T},
title = {Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42225822},
issn = {1476-5454},
abstract = {OBJECTIVES: To identify drug-associated risk signals for neovascular age-related macular degeneration (nAMD) and explore their biological basis.

METHODS: We analysed the US FDA Adverse Event Reporting System (FAERS) to detect drugs with disproportionate nAMD reporting. Drug targets were mapped and causality was assessed by integrating summary-based Mendelian randomisation (SMR) and colocalisation analyses using cis-pQTL data. Single-cell RNA sequencing from nAMD patients evaluated cell type-specific gene expression. Protein-protein interaction and pathway enrichment analyses elucidated underlying mechanisms.

RESULTS: FAERS analysis identified five drugs (apixaban, carbamazepine, latanoprost, rituximab and semaglutide) significantly associated with higher reporting risks of nAMD. SMR implicated six genes (IGFBP6, MAPKAPK2, NFKB1, RGMA, RNASE1 and WARS1) in nAMD risk, with evidence supporting colocalisation for WARS1. Most candidate genes were predominantly expressed in vascular remodelling endothelial cells, while WARS1 was also highly specific to monocytes. Enrichment analysis highlighted their critical involvement in immune and inflammatory responses, particularly within the Toll-like receptor, TNF and NF-kappa B signalling pathways.

CONCLUSIONS: This study suggests a potential association between specific drugs and nAMD and reveals six genes as their possible molecular basis, thereby providing prioritised candidate targets and testable biological hypotheses for subsequent experimental validation.},
}

@article {pmid42226100,
year = {2026},
author = {He, B and Chen, Y and Cai, P and Xi, R and Shen, X and Guo, S and Chen, J and Li, S and Wu, Y},
title = {Exendin-4 averts all-trans-retinal-driven damage to photoreceptors and the retina via the GLP-1R/PKA/CREB1 signaling axis.},
journal = {Cellular & molecular biology letters},
volume = {},
number = {},
pages = {},
doi = {10.1186/s11658-026-00952-6},
pmid = {42226100},
issn = {1689-1392},
support = {82471093//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Atrophic macular degeneration comprises dry age-related macular degeneration (AMD) and autosomal recessive Stargardt disease (STGD1). These disorders lead to irreversible blindness and still lack effective therapies. The rise of all-trans-retinal (atRAL) brought on by visual cycle disruption closely links to retinal atrophy in both conditions, yet the key downstream targets remain obscure. Exendin-4 (EX-4) is a natural glucagon-like peptide-1 receptor (GLP-1R) agonist. Recent clinical retrospective studies indicate that GLP-1R agonists such as exenatide (synthetic EX-4) can markedly lower the 5-year risk of developing dry AMD. Here, we sought to clarify the protective effect of natural EX-4 against retinal degeneration in atrophic macular degeneration linked to impaired clearance of atRAL.

METHODS: Cell and animal paradigms of STGD1 and dry AMD were generated by atRAL-loaded 661W cells and light-exposed Abca4[-/-]Rdh8[-/-] mice, respectively. RNA-sequencing, cell viability assays, morphometric analysis, annexin V/propidium-iodide staining using flow cytometry, quantitative polymerase chain reaction (qPCR), western blotting, immunofluorescence, electroretinography (ERG), fundus photography, hematoxylin and eosin (H&E) histology, and TUNEL staining were integrated to delineate the anti-apoptotic actions of EX-4 and to uncover its underlying protective mechanism.

RESULTS: GLP-1R/cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA)/cAMP response element-binding protein 1 (CREB1) signaling was markedly downregulated in atRAL-challenged 661W cells and in neural retina of light-exposed Abca4[-/-]Rdh8[-/-] mice. EX-4 reinstated this pathway, suppressed caspase-3 activation and DNA damage, and curtailed apoptosis in both cell and tissue contexts. Silencing of Glp1r or the PKA catalytic subunits by small interfering RNA (siRNA) abrogated EX-4-induced activation of the PKA/CREB1 axis in atRAL-loaded 661W cells. Pharmacologic blockade of CREB1 phosphorylation with the PKA inhibitor H-89 or the CREB1 inhibitor 666-15 largely nullified the DNA-protective and anti-apoptotic benefits conferred by EX-4 in 661W cells following atRAL exposure, suggesting that the GLP-1R/PKA/CREB1 signaling axis contributes to its cytoprotection action. More importantly, intraperitoneal injection of EX-4 significantly preserved retinal structure and function in Abca4[-/-]Rdh8[-/-] mice after exposure to light, and mitigated punctate lesions in the fundus.

CONCLUSIONS: EX-4 exerted anti-apoptotic and DNA-protective effects against atRAL-induced photoreceptor loss and retinal degeneration at least partially through activating the GLP-1R/PKA/CREB1 pathway. These findings suggest that GLP-1R agonists could serve as potential preventive therapeutics for atrophic macular degeneration associated with atRAL toxicity, including dry AMD and STGD1.},
}

@article {pmid42227867,
year = {2026},
author = {Palladino, L and Paglia, L and Meschiari, G and Altieri, F and Cesa, S and Iazzetti, A and Cairone, F},
title = {Structural and thermal stability assessment of repackaged bevacizumab using RT-PCR-based differential scanning fluorimetry and intrinsic fluorescence spectroscopy.},
journal = {Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners},
volume = {},
number = {},
pages = {10781552261457538},
doi = {10.1177/10781552261457538},
pmid = {42227867},
issn = {1477-092X},
abstract = {IntroductionBevacizumab is a humanized monoclonal anti-VEGF antibody widely used in oncology and ophthalmology for the treatment of age-related macular degeneration and diabetic macular edema. Its intravitreal administration requires galenic repackaging, raising concerns regarding physicochemical stability and sterility assurance during storage. This study evaluated the structural and thermal stability of repackaged bevacizumab stored at 4 °C for up to four weeks.MethodsStability was assessed using intrinsic fluorescence spectroscopy and differential scanning fluorimetry (DSF) performed on a real-time PCR platform. Structural integrity was monitored through fluorescence emission spectra, while thermal stability was determined by melting temperature (Tm) analysis over time.ResultsIntrinsic fluorescence showed a constant emission maximum at 338 nm throughout the storage period, indicating preservation of the tertiary structure. DSF analysis demonstrated stable thermal unfolding profiles, with no significant variation in Tm values between baseline (67.4 ± 0.3 °C) and four weeks (67.2 ± 0.4 °C; p > 0.05).ConclusionsRepackaged bevacizumab maintained structural integrity and thermal stability for up to four weeks under refrigerated storage conditions. These findings support refrigerated batch preparation under the tested conditions and highlight RT-PCR-based DSF as a practical quality-control tool for hospital pharmacy settings.},
}

@article {pmid42227873,
year = {2026},
author = {Karl, NAM and Schuhmayer, AC and Pomberger, L and Eidherr, M and Khalil, H and Kallab, M and Rothbächer, J and Strohmaier, C and Huemer, J and Bolz, M and Reisinger, AS},
title = {Difference in Ocular Perfusion Drop After Intravitreal Aflibercept in Patients with Neovascular AMD and Diabetic Macular Edema.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/02713683.2026.2679143},
pmid = {42227873},
issn = {1460-2202},
abstract = {PURPOSE: Vascular endothelial growth factor (VEGF) is a factor in the pathogenesis of Age-Related Macular Degeneration (AMD) and Diabetic Macular Edema (DME), yet they differ in pathogenesis. It has been shown that only patients with diabetic retinopathy have elevated VEGF levels in the aqueous humor. Intravitreal injections of anti-VEGF substances have been the gold standard in treating diseases for several years, but an impact on ocular perfusion has been assumed. This study aimed to investigate the effects of intravitreal aflibercept injection (IVI) on ocular perfusion in patients with AMD and DME.

METHODS: This prospective study included 36 eyes of 36 patients, with 18 patients having nAMD (n = 18) and 18 patients having DME (n = 18), all treated with IVI. Ocular perfusion was measured using Laser Speckle Flowgraphy (LSFG). The parameter Mean Blur Rate (MBR) reflects erythrocyte flow velocity and serves as an indirect marker of perfusion. MBR was measured at the optic nerve head (ONH). The device's software can analyze MBR in areas of major retinal vessels (MV) and in microperfusion areas of the tissue (MT). Measurements were conducted at three time points (before scheduled IVI, as well as 1 week and 4 weeks after).

RESULTS: In patients with AMD, significant decrease in MV was observed, while no significant change was noted for MV in patients with DME (Analysis of Variance, ANOVA, p = 0.04 vs. p = 0.2). However, both groups showed a significant decrease in MT (ANOVA, p < 0.001 for both groups).

CONCLUSION: The results indicate that retinal perfusion as measured with LSFG is less impaired in patients with DME following IVI treatment. This could be related to endothelial dysfunction, which appears to be restricted to retinal endothelial cells, as MT as a surrogate marker of choroidal perfusion showed a significant reduction in the DME group. Responses highlight physiological differences between retinal and choroidal capillaries.},
}

@article {pmid42229813,
year = {2026},
author = {Cai, CX and Toy, B and Martin, B and Fan, R and Westlund, E and Tran, D and Nishimura, A and Lee, H and Leng, T and Nagy, P and Mathioudakis, N and Zhang, L and Hribar, M and Chen, A and Armbrust, K and Goetz, K and Baxter, S and Boland, MV and Brown, EN and Tsui, E and Barkmeier, AJ and Wang, S and Mehta, N and Stocking, JC and O'Keefe, G and Lee, CS and Payne, PRO and O'Brien, WJ and DuVall, S and Alshammari, T and Falconer, T and Dorr, DA and Humes, I and McCoy, D and Adibuzzaman, M and Mahmood, R and Morgan-Cooper, H and Desai, P and Kothari, SY and Sena, A and Blacketer, C and Ostropolets, A and Shoaibi, A and Rao, G and Hripcsak, G and Ryan, P and Suchard, MA},
title = {Semaglutide and Neovascular Age-Related Macular Degeneration Among Adults with Type 2 Diabetes: An OHDSI Network Study.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.05.034},
pmid = {42229813},
issn = {1549-4713},
abstract = {OBJECTIVE: or Purpose: To investigate the potential association of semaglutide and neovascular age-related macular degeneration (NVAMD) DESIGN: Retrospective study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network during the study period from 12/1/2017-12/31/2024 SUBJECTS, PARTICIPANTS, AND/OR CONTROLS: Adults with type 2 diabetes (T2D) on semaglutide, other glucagon-like peptide-1 receptor agonists (GLP-1RAs) (dulaglutide, exenatide), or non-GLP-1RAs (empagliflozin, sitagliptin, glipizide) METHODS, INTERVENTION OR TESTING: The association between semaglutide and NVAMD was assessed using two approaches: an active-comparator cohort design and a self-controlled case-series (SCCS) analysis. The cohort design used propensity score-adjusted Cox proportional hazards models to estimate hazard ratios (HRs). The SCCS used conditional Poisson regression models to estimate incidence rate ratios (IRRs). A random-effects meta-analysis was used to generate network-wide HR and IRR estimates.

MAIN OUTCOME MEASURES: Two definitions of NVAMD, one based on condition codes alone (NVAMD-C) or condition codes and procedures (NVAMD-CP).

RESULTS: A total of 227,971 new users of semaglutide were included in the study. The risk of NVAMD among semaglutide users was similar to users of dulaglutide (NVAMD-C HR 0.57, 95% CI 0.21 to 1.57, P=.28; NVAMD-CP HR 0.25, 95% CI 0.05 to 1.27, P=.10), empagliflozin (NVAMD-C HR 0.98, 95% CI 0.54 to 1.79, P=.94; NVAMD-CP HR 0.79, 95% CI 0.38 to 1.64, P=.52), sitagliptin (NVAMD-C HR 2.08, 95% CI 0.90 to 4.83, P=.09; NVAMD-CP HR 1.80, 95% CI 0.55 to 5.86, P=.33), and glipizide (NVAMD-C HR 0.83, 95% CI 0.35 to 2.02, P=0.69; NVAMD-CP HR 0.50, 95% CI 0.21 to 1.19, P=.12). There was no evidence of increased or decreased risk for NVAMD associated with semaglutide exposure (NVAMD-C: incidence rate ratio [IRR] 0.92, 95% CI 0.67 to 1.26, P=.60; NVAMD-CP IRR 1.02, 95% CI 0.76 to 1.36, P=.92) nor any of the other GLP-1RA or non-GLP-1RAs.

CONCLUSIONS: We detected no differences in the risk of NVAMD associated with semaglutide use among adults with T2D.},
}

@article {pmid42229850,
year = {2026},
author = {Hallaj, S and Nishida, T and Kamalipour, A and Longhurst, CA and Freeman, WR and Baxter, SL and Boussina, A},
title = {Glucagon Like Peptide 1 Receptor Agonists and Age-Related Macular Degeneration Incidence.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.05.016},
pmid = {42229850},
issn = {2468-6530},
abstract = {PURPOSE: To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes.

DESIGN: Retrospective, propensity score-matched cohort study.

PARTICIPANTS: Adults with diabetes initiating a GLP-1RA or another non-insulin antidiabetic agent. In Epic Cosmos, 2,797,686 GLP-1RA users were matched 1:1 to 2,797,686 active comparators.

METHODS: We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-vascular endothelial growth factor treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models.

MAIN OUTCOME MEASURES: Incident any AMD and incident nAMD.

RESULTS: In the matched Epic Cosmos cohort (total N=5,595,372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% CI, 0.182%-0.192%] vs 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs 6.540% [95% CI, 6.017%-7.108%]); all P<.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs 0.065%), 5 years (0.280% vs 0.340%), and 10 years (1.874% vs 2.393%); all P<.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P<.001) and was not associated with increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P=.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups.

CONCLUSIONS: Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes.},
}

@article {pmid42218984,
year = {2026},
author = {Hyttinen, JMT and Salminen, A and Kauppinen, A and Kaarniranta, K},
title = {The role of Wnt signalling in the pathogenesis and therapy of age-related macular degeneration (AMD).},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {118114},
doi = {10.1016/j.bcp.2026.118114},
pmid = {42218984},
issn = {1873-2968},
abstract = {Age-related macular degeneration (AMD) is an ever-increasing disease which affects the vision of the elderly in the Western world. No preventive therapy exists so far and slowing its progression is only possible for a fraction of the cases, namely neovascular AMD, in which neovascularisation sprouts from the choriocapillaris layer into the retina. Nevertheless, one potential target for modulation as an AMD therapy is the manipulation of Wnt signalling, and especially its canonical type, the Wnt/β-catenin pathway. Wnt signalling is one of the fundamental cellular pathways involved e.g. in morphogenesis, proliferation, cell polarity, tissue maturation, as well as homeostasis, and apoptosis. The rationale of modulating Wnt signalling in AMD therapy, is that weakened autophagy, autophagy, the means of the cell to remove waste material, as well as increased epithelial-mesenchymal cell type transition (EMT), inflammation, and oxidative stress response have been detected in AMD. Corresponding to these, the upregulation of Wnt signalling pathway has been discovered to be related to this disease. Thus, inhibition of Wnt signalling could be used as in therapy, especially in the more common, dry form of AMD in all its stages. On the other hand, the activation of Wnt signalling could be used in the therapy of advanced neovascular AMD, primarily for maintaining the blood-retinal barrier, which preserves the homeostasis of the retinal vasculature. Therefore, several approaches concerning both the inhibition and upregulation of Wnt signaling are discussed in this review, in the context of potentially developing effective therapies against AMD in the future.},
}

@article {pmid42219076,
year = {2026},
author = {Mikhail, D and Tao, BK and Yu, P and Calicchia, L and Butt, FR and Dhivagaran, T and Al-Qattan, HM and Feo, A and Quarta, A and Mishra, AV and Seamone, ME and Navajas, EV and Kertes, PJ and Wong, DT and Muni, RH and Kaplan, AJ and Yan, P and Popovic, MM},
title = {Risk of Retinal Detachment After Intravitreal Injection of Anti-VEGF: A Systematic Review and Meta-Analysis.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.05.042},
pmid = {42219076},
issn = {1879-1891},
abstract = {TOPIC: This systematic review and meta-analysis evaluated the literature-pooled risk of retinal detachment (RD) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents.

CLINICAL RELEVANCE: Intravitreal anti-VEGF injections are the most frequently performed intraocular procedure, with RD remaining a poorly quantified complication. Pooled estimates equip clinicians to contextualize RD risk during informed consent.

METHODS: This systematic review and meta-analysis followed PRISMA guidelines (PROSPERO: CRD420251175527). MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to January 18, 2026. Included studies reported RD risk after anti-VEGF IVI for neovascular age-related macular degeneration (nAMD), diabetic macular edema, macular edema from retinal vein occlusion, proliferative diabetic retinopathy, or myopic choroidal neovascularization. Paired reviewers independently extracted data and assessed risk of bias using ROBINS-I and the Joanna Briggs Institute checklist for case series. A random-effects single-arm meta-analysis of proportions using a generalized linear mixed model generated pooled risk estimates per injection and per eye.

RESULTS: Twelve studies comprising 834,814 injections and 119 RD events were included. In the meta-analysis of 9 studies (787,849 injections), there were 92 rhegmatogenous RD (RRD) events, with a pooled risk of 0.012% [95% CI (0.009-0.015%), I²: 14.4%], equivalent to 1 in 8675 injections. An acute ≤90-day postprocedural sensitivity analysis yielded a consistent RRD risk of 0.013% [95% CI (0.010-0.016%), I²: 36.8%] (approximately 1 in 7692 injections). An eye-level sensitivity analysis yielded a per-eye risk of 0.08% [95% CI (0.02-0.31%), I²: 66.7%] (approximately 1 in 1250 eyes). Exploratory subgroup analyses showed no differences in RRD risk by injection number (≥100,000 vs. <100,000; P=0.520), study setting (single-center vs. multicenter; P=0.258), injection indication (nAMD only vs. mixed; P=0.061), injection provider (ophthalmologist vs. mixed; P=0.259), or risk of bias (P=0.356). One study evaluating severe PDR reported tractional RD risk as 3.6% [95% CI (2.3-5.2%)] (approximately 1 in 28 injections), likely reflecting disease-specific fibrovascular contraction.

CONCLUSION: Low-certainty evidence indicates RRD following anti-VEGF IVI is uncommon, with a per-injection risk of 0.012% (1 in 8675 injections). Per-eye risk was 0.08% (1 in 1250 eyes), which was subject to wider uncertainty but more relevant to patients undergoing long-term treatment; notably, the pooled mean of 13.8 injections per eye in the contributing studies likely underestimates real-world cumulative exposure. Future work should incorporate eye-level denominators and standardized reporting of RD subtypes, ocular characteristics, and injection technique to enable risk stratification and identification of modifiable procedural contributors.},
}

@article {pmid42219104,
year = {2026},
author = {Maiti, S and Joseph, J},
title = {From Systemic Disease to the Eye: Why Senescence Deserves Attention in Ocular Infections.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111095},
doi = {10.1016/j.exer.2026.111095},
pmid = {42219104},
issn = {1096-0007},
abstract = {The global increase in life expectancy has led to a growing elderly population, bringing new challenges in managing infectious diseases. Advancing age is accompanied by progressive dysfunction of both innate and adaptive immunity, resulting in impaired responses to pathogens and elevated morbidity and mortality. Cellular senescence, a state of permanent cell-cycle arrest with extensive molecular and phenotypic changes, including chromatin remodeling and the senescence-associated secretory phenotype (SASP), has emerged as a key factor in this process. Though initially protective as a tumor-suppressive mechanism, senescence becomes maladaptive with age, contributing to inflammaging, immune dysregulation, and heightened susceptibility to infection. In ocular diseases, such as age-related macular degeneration and chronic keratitis, senescent cells in retinal pigment epithelium and corneal tissues drive persistent inflammation and fibrosis, exacerbating vulnerability to opportunistic pathogens. Pathogens can exploit senescent cells through virulence factors and persistent inflammatory responses, thereby promoting chronic infection and even age-related diseases. Conversely, senescent cells and their SASP can intensify infection severity, as shown in viral infections such as SARS-CoV-2 and bacterial pathogens including Streptococcus pneumoniae and Mycobacterium tuberculosis. This reciprocal relationship illustrates how infection accelerates cellular aging while aging predisposes individuals to more severe infections. Emerging therapeutic strategies targeting senescence, including senolytics and senomorphics, hold promise for mitigating infection-related pathology. In parallel, vaccines and immunotherapies tailored to the aging immune system will be crucial for reducing infection burden in older populations. This review integrates current evidence on the bidirectional interplay between senescence and infection, emphasizing its clinical relevance and potential for translational intervention.},
}

@article {pmid42221036,
year = {2026},
author = {Zhu, Y and Gumustop, SS and Wang, L and Tong, A and Ding, X and Ploumi, I and Romano, F and Chen, C and Nodecker, KN and Shah, SH and Wagner, SL and Vavvas, DG and Husain, D and Miller, JW and Patel, NA and Kim, LA and Wu, DM and Miller, JB},
title = {Influence of Anti-VEGF Injections on Longitudinal Changes in Vascular Metrics Measured by OCTA in Age Related Macular Degeneration: A Retrospective Real-World Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {561121},
pmid = {42221036},
issn = {1177-5467},
abstract = {PURPOSE: To investigate the possible influence of repeated anti-VEGF injections on vascular metrics measured by optical coherence tomography angiography (OCTA) in patients with age-related macular degeneration (AMD).

METHODS: This retrospective longitudinal study included AMD patients with a follow-up time of at least 18 months from 2019 to 2024. Swept-source OCTA was performed on all eyes. Based on whether an eye received injections or not during follow-up, all eyes were divided into two groups (non-injection group only included non-exudative AMD). Vessel density, Vessel skeleton density in the superficial, deep, and retina slab, as well as foveal avascular zone (FAZ) size, circularity and perimetry of Angio 6mm×6mm were calculated. Change in vascular metrics between baseline and last follow-up were compared between the two groups using t-test or Mann-Whitney U-test. Correlation between change in vascular metrics and visual acuity was investigated by Spearman's Rank Correlation test.

RESULTS: A total of 164 eyes from 107 patients were included. The average follow-up time was 34 months. No statistically significant difference in baseline vascular metrics was detected between the injection group (57 eyes) and non-injection (107 eyes) group. The injection group received 12.56 injections during follow-up. Among all the parameters, only change in FAZ size during follow-up showed a statistically significant difference between the two groups (0.03 vs. 0.02 mm[2], P=0.043). No correlation was found between change in vascular metrics and change in visual acuity (P>0.05).

CONCLUSION: In this retrospective longitudinal study of 164 eyes, repeated intravitreal anti-VEGF injections were associated with no relevant significant changes in OCTA vascular metrics over time.},
}

@article {pmid42221039,
year = {2026},
author = {Swarnkar, PK and Singh Bhangu, J and Stewart, C and Rifat, M and Khalid, S and Winkworth, H and Franklin-Goddard, SL and Awad, MH and Williams, GS},
title = {Challenging the Treatment Threshold: Early Faricimab Prevents Vision Loss in nAMD - A Real-World Welsh Experience.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {604687},
pmid = {42221039},
issn = {1177-5467},
abstract = {PURPOSE: To compare real-world outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients initiated on Faricimab at early (<0.3 logMAR) versus late (0.6-0.7 logMAR) visual thresholds.

METHODS: Retrospective, single-centre cohort study of 97 patients (53 early, 44 late) treated at a UK centre, with three monthly loading doses followed by treat-and-extend. Outcomes: BCVA change, vision loss (≥5 letters), stable vision at 6/12/18 months, injection intervals, extension >8 weeks, dry macula.

RESULTS: Baseline VA was 74 ± 3.5 letters (early) vs 54 ± 2.0 letters (late), p<0.001. No early patient experienced sustained vision loss at 6, 12, or 18 months compared with 76.7%, 73.3%, and 75.0% of late patients, respectively (p<0.05 for all). At the 7th injection, 67.6% of late patients lost ≥5 letters vs 14.9% of early patients (ARR 52.7%, p<0.001). Cumulatively, 81.8% of late patients experienced ≥5-letter loss vs 41.5% of early patients (ARR 40.3%, NNT 3, p<0.001). Mean injection intervals were similar, but the early cohort sustained extension beyond 8 weeks in >50% of eyes from the 4th-5th interval onward. In contrast, the late cohort exhibited a biphasic collapse, with extension rates declining from 62.2% at 6th-7th to only 35.0% by 9th-10th. Despite a significant baseline anatomical disadvantage (18.9% vs 50.0% dry macula, p=0.001), the early cohort achieved 100% dryness by 18 months compared with 96.7% in the late cohort, with crossover occurring by 12 months (95.8% vs 89.7%, p=0.269).

CONCLUSION: In this retrospective, single-centre study, early faricimab initiation was associated with preservation of high-function vision, a lower risk of clinically significant vision loss, and high rates of anatomical quiescence and durable treatment extension. These findings suggest that proactive early intervention may offer advantages over reactive treatment paradigms, although confirmation in larger, prospective, and multi-centre studies is needed.},
}

@article {pmid42221729,
year = {2026},
author = {Zhao, AH and Alam, TA and Das, N and Maatouk, C and Singh, RP and Talcott, KE},
title = {Long-Term Predictive Value of Macular Thickness Fluctuations in Response to Anti-VEGF Treatment for Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261448432},
pmid = {42221729},
issn = {2474-1272},
abstract = {Purpose: To evaluate whether macular thickness fluctuations are predictive of long-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) after treatment initiation with antivascular endothelial growth factor (anti-VEGF). Methods: Patients with nAMD treated with anti-VEGF intravitreal injections for 3 and 5 years were evaluated. Anatomic parameters, including central subfield thickness (CST), were evaluated with optical coherence tomography. The cohort was segregated into quartiles based on CST variability over the initial 12 months of treatment. Kruskal-Wallis tests were used to compare 3- and 5-year final best-corrected visual acuity (BCVA), change in BCVA, final CST, and change in CST among quartiles. Multiple linear regression analyses were subsequently performed. Results: Three hundred sixty-six eyes were included in the 3-year analysis and 275 eyes in the 5-year analysis. Patients received an average of 8.4 injections over 12 months and had a final mean BCVA of 60.7 Early Treatment Diabetic Retinopathy Study letters. Those with the greatest CST variability demonstrated significantly lower baseline and final BCVA compared with other quartiles, alongside lower baseline BCVA values. No difference was found between quartiles for final CST and change in BCVA. Multiple linear regression analyses demonstrated that macular thickness variability characterized by the standard deviation of CST, baseline VA, and age was a significant predictor of VA after 3 and 5 years. Conclusions: Macular thickness variability was a statistically significant correlate and limited predictor of long-term response to visual outcomes at 3 and 5 years after anti-VEGF initiation. Macular thickness variability may be a biomarker with limited long-term predictive value in patients with nAMD.},
}

@article {pmid42221733,
year = {2026},
author = {Salabati, M and Mallepally, A and Farhani, K and Mahmoudzadeh, R and Brar, V and Randolph, J},
title = {The Effect of Acetylcholinesterase Inhibitors and N-Methyl-D-Aspartate Receptor Antagonists on the Risk of Development and Progression of Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261450196},
pmid = {42221733},
issn = {2474-1272},
abstract = {Purpose: To investigate whether memantine or acetylcholinesterase inhibitors are associated with reduced risk of developing age-related macular degeneration (AMD) and of progression from nonexudative to exudative AMD. Methods: This retrospective cohort study used data from the TriNetX US Collaborative Network between 2008 and 2023. Adults 50 years and older were included and categorized into AMD-naïve and dry AMD cohorts. Exposure groups were defined by outpatient prescriptions for acetylcholinesterase inhibitors (donepezil, rivastigmine, or galantamine) or memantine. Each exposure group was propensity score-matched 1:1 to unexposed controls based on demographic and clinical characteristics. Outcomes were incident AMD in the AMD-naïve cohort and incident exudative AMD in the dry AMD cohort at least 1 year after the prescription. Risk ratios (RRs) and 95% CIs were estimated, and memantine was compared with acetylcholinesterase inhibitors in a head-to-head analysis. Results: Among AMD-naïve patients, acetylcholinesterase inhibitor use (n = 35 397) and memantine use (n = 13 576) were associated with lower AMD incidence compared with matched controls (RR, 0.490; 95% CI, 0.442-0.543; P < .001; and RR, 0.532; 95% CI, 0.448-0.630; P < .001, respectively). In patients with dry AMD, both acetylcholinesterase inhibitors and memantine were associated with reduced progression to exudative AMD (RR, 0.448; 95% CI, 0.357-0.562; P < .001; and RR, 0.552; 95% CI, 0.362-0.842; P = .005). In head-to-head comparisons, similar risks for incident AMD were seen with memantine and acetylcholinesterase inhibitors (RR, 0.929; 95% CI, 0.762-1.132; P = .46) and progression to exudative AMD (RR, 1.198; 95% CI, 0.720-1.994; P = .49). Conclusions: Memantine and acetylcholinesterase inhibitors were associated with a reduced risk of AMD development and progression. These findings support further investigation into shared neuroprotective pathways and potential drug repurposing.},
}

@article {pmid42222587,
year = {2026},
author = {Mercuri, S and Sacu, S and Frank-Publig, S and Schrittwieser, J and Gumpinger, M and Leingang, O and Schmidt-Erfurth, U and Chakravarthy, U and Bogunovic, H and Virgili, G and Reiter, GS},
title = {Fluid Volumes Longitudinal Modeling to Predict Atrophy and Fibrosis in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {6},
pages = {101190},
pmid = {42222587},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the impact of retinal fluid volumes on the development of atrophy and fibrosis in neovascular age-related macular degeneration (nAMD) during routine care.

DESIGN: Retrospective longitudinal study.

PARTICIPANTS: Treatment-naïve eyes with nAMD from the Vienna Imaging Biomarker Eye Study (2007-2018), initiating anti-VEGF therapy.

METHODS: Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were automatically quantified on OCT using an approved artificial intelligence algorithm within the 1-, 3-, and 6-mm ETDRS regions. Macular neovascularization (MNV) type and baseline presence of subretinal hyperreflective material (SHRM) were assessed. Fluid volumes were modeled as time-dependent biomarkers using repeated-measure Cox models to evaluate cumulative effects over time on the development of atrophy and fibrosis, with hazard ratios calculated for quartiles (Qs) at each visit. Associations with change in visual acuity (VA) were performed in a subset of eyes with ≥12 months of follow-up.

MAIN OUTCOME MEASURES: Retinal fluid volumes, development of atrophy and fibrosis, and change in VA.

RESULTS: A total of 1060 eyes of 998 patients were included. Higher IRF volumes increased the risk of both atrophy and fibrosis (all P < 0.001). Subretinal fluid reduced the risk of atrophy (Q4, P ≤ 0.001) and fibrosis (1-mm, P = 0.028) in the 1- and 3-mm regions, but increased the risk of fibrosis in the 6-mm region (P ≤ 0.031). Higher PED volumes increased the risk of atrophy in the 6-mm region (P < 0.001), and fibrosis at all locations (P ≤ 0.002). Age and baseline presence of SHRM were associated with atrophy (P < 0.001), whereas type 2 and mixed/undefined MNVs were associated with both atrophy (P < 0.001) and fibrosis (P ≤0.004). In 552 eyes, time-related presence of fibrosis was associated with VA decline at all locations (P < 0.001). In all areas, Q4 of IRF was associated with linear VA decline (P <0.001). Larger SRF volumes (Q4) in the 1-mm region were associated with better vision (P <0.05). Higher PED volumes (Q3, Q4) were linked to VA decline at all locations (P < 0.001).

CONCLUSIONS: Assessment of the cumulative effects of retinal fluid volumes during anti-VEGF therapy using time-dependent biomarker modeling revealed notable associations with risk of atrophy, fibrosis, and VA decline.

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

@article {pmid42222588,
year = {2026},
author = {de Breuk, A and de Jong, S and Bakker, B and Kersten, E and Luttikhuizen, DT and Fauser, S and Klaver, CCW and den Hollander, AI and Hoyng, CB and Lechanteur, YTE},
title = {Geographic Atrophy in Patients with Age-Related Macular Degeneration Is Associated with Rare Variants in Complement Factor H and Complement Factor I.},
journal = {Ophthalmology science},
volume = {6},
number = {6},
pages = {101171},
pmid = {42222588},
issn = {2666-9145},
abstract = {PURPOSE: To describe the phenotype of patients with age-related macular degeneration (AMD) carrying rare genetic variants in the complement factor H (CFH) and complement factor I (CFI) genes.

DESIGN: Cross-sectional study.

PARTICIPANTS: Two hundred thirty-four patients with AMD carrying rare variants in CFH (n = 134) and CFI (n = 100) and 234 AMD noncarriers.

METHODS: Genetic data of patients with AMD from the European Genetic Database were filtered for rare coding and splice-site variants in CFH and CFI. For each carrier, an age-matched (±2 years) patient with AMD without rare variants in CFH and CFI (noncarrier) was selected. Phenotypic characteristics on color fundus photographs were graded according to the Rotterdam Classification and compared between carriers and noncarriers by univariate generalized estimating equations with binary logistic regression analyses, applying a Bonferroni correction for multiple comparisons. We performed subanalyses for pathogenic rare variants only, and we analyzed CFH and CFI carriers separately.

MAIN OUTCOME MEASURES: Phenotypic characteristics on color fundus photographs.

RESULTS: Geographic atrophy and intermediate AMD, along with features such as predominant drusen type, largest drusen size, and drusen area, were associated with carriership of rare pathogenic variants in CFH (P < 0.001, P = 0.002, P < 0.001, and P < 0.001, respectively). Geographic atrophy and intermediate AMD, along with features such as drusen size, drusen area, and pigmentation, were associated with carriership of rare pathogenic variants in CFI (P = 0.01, P = 0.006, P < 0.001, and P = 0.006, respectively). Furthermore, carriers of rare pathogenic variants in CFH were younger (P < 0.001) and had a lower genetic risk score for common AMD-associated variants compared with noncarriers (mean [standard deviation] genetic risk score 0.83 [1.01] vs. 1.41 [1.21], P = 0.03).

CONCLUSIONS: In this study, patients with AMD carrying rare variants in CFH and CFI had a more severe drusen phenotype, and a higher frequency of geographic atrophy at a relatively early age. Identifying this distinct phenotype could aid in pinpointing individuals who are more likely to benefit from complement-inhibiting therapies.

FINANCIAL DISCLOSURES: The authors have no proprietary or commercial interest in any materials discussed in this article.},
}

@article {pmid42215276,
year = {2026},
author = {Guo, X and Chen, Y and Yao, J and Huang, J and Xiong, R and Han, X and Huang, W and Congdon, N and Wang, W},
title = {Trends of blindness and visual impairment in individuals aged 70 and older.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328311},
pmid = {42215276},
issn = {1468-2079},
abstract = {BACKGROUND: The global ageing population has heightened the importance of eye health, yet comprehensive assessments of blindness and vision impairment (BVI) burden among older adults remain limited. Using Global Burden of Disease 2021 data, we analysed trends and disparities in BVI and major eye diseases across 204 countries and territories from 1990 to 2021 among adults aged ≥70 years.

METHODS: Age-standardised prevalence (ASPR), years lived with disability, and average annual percentage change (AAPC) were estimated for BVI and its leading causes, stratified by age, sex, region and Sociodemographic Index (SDI). Temporal trends were assessed using joinpoint regression.

RESULTS: Globally, between 1990 and 2021, the number of BVI cases increased 156% (94.5 to 242 million) with an AAPC of 0.11%. Women experienced a faster rise in ASPR than men (AAPC 0.16% vs 0.11%). Age-specific analysis revealed divergent trends: prevalence rose in the 70-84 age group (peak AAPC 1.02% in 70-74 years) but declined in those ≥85 years (AAPC -0.23% in 85-89 years). With increasing SDI, the prevalence rate for BVI and major blinding eye diseases significantly decreased (p<0.001). Regionally, high-income North America showed the largest ASPR reductions (AAPC -0.30%).

CONCLUSIONS: Demographic expansion and ageing are the primary drivers of the rise in absolute BVI burden among adults aged ≥70 years since 1990, with persistent inequities across sex and SDI levels. Further country-specific analyses, particularly in settings with limited primary data, will help refine estimates and support future research and service planning.},
}

@article {pmid42215633,
year = {2026},
author = {Zhu, J and Zeng, C and Tang, R and Lu, W and Wang, S and Huang, L and Xiong, Z and Deng, A and Zhen, Z and Chen, R and Li, X},
title = {Causal relationship between aspirin use and age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42215633},
issn = {1476-5454},
support = {82220108016//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {OBJECTIVE: Although increasing evidence suggests an association between aspirin use and age-related macular degeneration (AMD), the potential causal relationship between them remains controversial. This study aims to explore the causal genetic association and potential mediators between aspirin use and AMD using Mendelian randomisation (MR) analysis.

METHODS: A bidirectional, two-sample, two-step MR analysis was performed to assess the potential causal relationships among aspirin use, AMD, and possible mediators. Multivariable MR was additionally performed to estimate the direct effect of aspirin use on AMD after adjusting for mediators. Causal estimates were primarily derived using an inverse variance weighted method. Horizontal pleiotropy, heterogeneity, and stability were evaluated using the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis.

RESULTS: An MR analysis revealed that aspirin use was associated with an increased risk of both early and dry AMD. A mediation analysis indicated that aspirin use is associated with a lower level of serum low-density lipoprotein cholesterol (LDL-C), an elevated serum apolipoprotein A1 (APOA1) concentration, and an increased risk of early and dry AMD. Multivariable MR analysis further showed that after adjusting for LDL-C and APOA1, the direct effect of aspirin on AMD was attenuated to non-significance.

CONCLUSION: This study provides robust genetic evidence that aspirin use is associated with an increased risk of early and dry AMD, and demonstrates that this association is fully mediated by decreased serum LDL-C and increased serum APOA1 levels, with no evidence of a direct effect independent of these lipid pathways.},
}

@article {pmid42216114,
year = {2026},
author = {Ji, PX and Herman, JE and Sivachandran, N},
title = {Rapid resolution of submacular hemorrhage in neovascular age-related macular degeneration using pneumatic displacement and faricimab.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04978-4},
pmid = {42216114},
issn = {1471-2415},
abstract = {BACKGROUND: Submacular hemorrhage (SMH) is a rare but visually devastating complication of neovascular age-related macular degeneration (nAMD) associated with poor long-term prognosis due to photoreceptor iron toxicity, subretinal fibrosis, and retinal pigment epithelial (RPE) damage. Pneumatic displacement (PD) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy is an established approach for managing acute SMH; however, the role of faricimab, a novel dual inhibitor of VEGF-A and angiopoietin-2 (Ang-2), in this context has not been previously evaluated.

CASE PRESENTATION: This study reports the outcomes of PD combined with faricimab injection in a case of a 75-year-old female with acute SMH secondary to nAMD. The patient with dense SMH and a large PED secondary to presumed polypoidal choroidal vasculopathy (PCV) underwent PD with 0.40 mL of sulfur hexafluoride and intravitreal faricimab injection (50 µL, 6 mg) on the same day as presentation, followed by 5 days of face-down positioning with excellent patient compliance confirmed by verbal verification. Two additional faricimab injections were administered at 4 and 8 weeks, followed by treat-and-extend protocol.

CONCLUSIONS: The use of timely PD with appropriate head positioning can effectively manage patients with acute large SMH and improve visual outcomes. While the combined approach with serial faricimab injections showed longer-term benefits, the immediate improvement was likely due to mechanical techniques. The potential added benefit of faricimab's dual inhibition mechanism over other anti-VEGF therapies in SMH remains to be investigated through larger, comparative trials.},
}

@article {pmid42217617,
year = {2026},
author = {Kaushik, S and Bisen, S and Singh, NK},
title = {Retinal pericytes and their role in proliferative retinopathies.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2026.04.021},
pmid = {42217617},
issn = {1525-2191},
abstract = {Vascular dysfunction and abnormal vascularization are primary characteristics of many proliferative retinopathies. Research on proliferative retinopathies has primarily focused on understanding the role of cells and factors that regulate endothelial cell function in ischemic retinopathies. Pericyte coverage of the retina is deemed essential for the survival of endothelial cells, and recently significant efforts have been made to comprehend the role of pericytes under stress conditions such as diabetes and ischemia. Understanding the significance of retinal pericytes in proliferative retinopathies is essential, particularly because of the often-contradictory findings reported regarding their role in these conditions. This review will not only explore the role of retinal pericytes and their interactions with retinal endothelial cells in physiological vascularization but also highlight its importance in the pathogenesis of retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion. A deeper comprehension of pericyte-endothelial interactions in proliferative retinopathies would aid in diagnosis and the formulation of viable therapeutics to avert vision loss associated with these proliferative retinopathies.},
}

@article {pmid42217724,
year = {2026},
author = {Harris, C and Nisar, MA and Amamoo, R and Patel, R and Martin, PM and Jadeja, RN and Thounaojam, MC},
title = {Murine Models of Neovascular AMD Revisited: Mechanistic Pathways, Immune-Metabolic Crosstalk, and the Impact of Aging and Sex.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111094},
doi = {10.1016/j.exer.2026.111094},
pmid = {42217724},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Neovascular AMD (nAMD) is characterized by choroidal neovascularization (CNV), vascular leakage, and fibrotic remodeling. Although anti-vascular endothelial growth factor (VEGF) therapy has improved visual outcomes for some patients, emerging findings highlight growing concerns regarding treatment resistance, persistent disease activity, and progression to subretinal fibrosis, which remain major challenges. Growing evidence indicates that nAMD arises from the interplay among metabolic dysfunction, oxidative stress, chronic inflammation, hypoxia signaling, and extracellular matrix remodeling within the outer retina. Disruption of mitochondrial function, lipid handling in the retinal pigment epithelium, complement activation, inflammasome signaling, macrophage immune-metabolic reprogramming, and hypoxia-driven VEGF expression collectively shape angiogenesis and lesion progression. Murine models, including laser-induced CNV, two-stage laser-induced fibrosis, and spontaneous or genetic systems such as JR5558, VLDLR-deficient, and CYP27A1-deficient mice, have provided essential mechanistic insights into these pathways. Aging and biological sex influence metabolism, mitochondrial efficiency, immune responses, hypoxia responsiveness, and wound-healing capacity. However, many widely used experimental models rely on young adult animals and often use a single sex without accounting for sex- or age-based differences, leaving these critical factors understudied and inadequately integrated into preclinical design. This review integrates current mechanistic understanding with a critical evaluation of murine nAMD models and emphasizes the importance of incorporating biological age and sex into experimental systems to improve mechanistic interpretation and translational relevance.},
}

@article {pmid42217973,
year = {2026},
author = {Lankry, P and Loewenstein, A and Trivizki, O},
title = {Insights into age-related macular degeneration.},
journal = {Handbook of clinical neurology},
volume = {218},
number = {},
pages = {165-190},
doi = {10.1016/B978-0-443-22212-2.00020-3},
pmid = {42217973},
issn = {0072-9752},
mesh = {Humans ; *Macular Degeneration/epidemiology/therapy/diagnosis ; Risk Factors ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Age-related macular degeneration (AMD) is a complex and prevalent ocular condition with significant implications for vision and quality of life in the aging population. This chapter provides a comprehensive exploration of AMD, encompassing its multifactorial pathophysiology, epidemiologic trends, and associated risk factors. A detailed examination of the distinct features and symptoms characterizing neovascular and dry AMD enhances our understanding of the clinical spectrum. Special emphasis is placed on geographic atrophy (GA), an advanced stage of AMD, highlighting its significant impact on visual outcomes. Apart from examining the present diagnostic methods and criteria for AMD, this chapter assesses current therapeutic approaches, with a specific emphasis on antivascular endothelial growth factor (anti-VEGF) treatments. Additionally, the discussion extends to emerging therapies and potential avenues for future research in AMD. Preventative strategies and lifestyle modifications that may influence disease progressions are also reviewed. By consolidating current knowledge, clinical insights, and future prospects, this chapter aims to serve as a valuable resource for clinicians, researchers, and students engaged in the study and management of age-related macular degeneration.},
}

Humans
*Macular Degeneration/epidemiology/therapy/diagnosis
Risk Factors
Angiogenesis Inhibitors/therapeutic use

@article {pmid42217980,
year = {2026},
author = {Winebrake, JP and Lim, JI},
title = {Retinal imaging and artificial intelligence analysis.},
journal = {Handbook of clinical neurology},
volume = {218},
number = {},
pages = {3-12},
doi = {10.1016/B978-0-443-22212-2.00011-2},
pmid = {42217980},
issn = {0072-9752},
mesh = {Humans ; *Artificial Intelligence ; *Retina/diagnostic imaging ; Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnostic imaging ; },
abstract = {The retina, uniquely accessible as an extension of the central nervous system, plays a critical role in neurology and ophthalmology. Advances in retinal imaging technologies - including color fundus photography, optical coherence tomography, and OCT angiography - have enabled detailed, noninvasive assessment of ocular and systemic diseases. Artificial intelligence (AI), particularly deep learning, has revolutionized the analysis of these images, facilitating early detection, classification, and prognostication of conditions such as diabetic retinopathy, age-related macular degeneration, optic neuropathies, and inherited retinal diseases. AI applications extend beyond ophthalmology, offering insights into neurologic and cerebrovascular disorders through retinal biomarkers. However, challenges remain regarding dataset bias, generalizability, ethical concerns, and the "black box" nature of AI models. Addressing these limitations, along with integrating multimodal imaging and fostering cross-specialty collaboration, will be pivotal in ensuring that AI technology is adopted effectively and responsibly. The future will be marked by synergistic AI-human workflows to enhance diagnostic accuracy, screening scalability, and personalized patient care. As AI applications evolve, they promise to reshape retinal imaging and its intersection with neurology, expanding opportunities for early intervention and improved outcomes.},
}

Humans
*Artificial Intelligence
*Retina/diagnostic imaging
Tomography, Optical Coherence/methods
*Retinal Diseases/diagnostic imaging

@article {pmid42217982,
year = {2026},
author = {Jones, BW},
title = {Insights into retinal remodeling in retinal degenerative disease.},
journal = {Handbook of clinical neurology},
volume = {218},
number = {},
pages = {327-339},
doi = {10.1016/B978-0-443-22212-2.00015-X},
pmid = {42217982},
issn = {0072-9752},
mesh = {Humans ; *Retinal Degeneration/pathology/physiopathology ; Animals ; *Neuronal Plasticity/physiology ; *Retina/pathology/physiopathology ; },
abstract = {The retina is a highly organized sensory structure responsible for capturing and processing visual information. Visual computation begins at the first synapse between photoreceptors, bipolar cells, and horizontal cells, before involving amacrine and ganglion cells to generate vision. Retinal degeneration disrupts the precise neural architecture required for vision, initiating a maladaptive process known as retinal remodeling. Photoreceptor degeneration in diseases, like retinitis pigmentosa (RP) and age-related macular degeneration, induces retinal remodeling, but good evidence shows glaucoma and diabetic retinopathy do as well, expanding the clinical significance. Historically, studies relied on histologic measures that assumed photoreceptor degeneration marked disease endpoints. However, retinal remodeling involves extensive structural and functional reorganization across all retinal cell classes, driven by the interdependence between neurons, glia, and the retinal pigment epithelium. Retinal plasticity corrupts normal retinal computations, and recent evidence suggests therapeutic windows close after ∼50% photoreceptor loss. Understanding remodeling mechanisms is critical for effective therapies, as current treatments fail to address the ongoing negative plasticity. Insights from retinal remodeling offer broader implications for neurodegeneration, highlighting the retina as a model for understanding central nervous system diseases like Alzheimer and Parkinson. Advancing knowledge of these processes will be pivotal for developing interventions to preserve vision.},
}

Humans
*Retinal Degeneration/pathology/physiopathology
Animals
*Neuronal Plasticity/physiology
*Retina/pathology/physiopathology

@article {pmid42217985,
year = {2026},
author = {Wang, J and Felfeli, T and Ballios, BG},
title = {Stem cell therapy in retinal disease.},
journal = {Handbook of clinical neurology},
volume = {218},
number = {},
pages = {365-385},
doi = {10.1016/B978-0-443-22212-2.00004-5},
pmid = {42217985},
issn = {0072-9752},
mesh = {Humans ; Animals ; *Stem Cell Transplantation/methods ; *Retinal Diseases/therapy/surgery ; Stem Cells/physiology ; },
abstract = {Stem cell therapy presents a new solution to cure degenerative diseases of the retina, which normally have limited ability to regenerate after injury. Stem cells are cells capable of self-renewal and differentiation into more specialized cells, and can be derived from both embryonic and adult sources. This definition encompasses a heterogeneous group of cells possessing varied potency and characteristics. Current attempts in applying stem cell technology to the retina have primarily focused on regenerating the retinal pigment epithelium (RPE) and light-sensing photoreceptor cells. They have not only shown the ability to prevent the death of host photoreceptors, but they can also differentiate into all major retinal cell types to replace lost cells. In vivo experiments, primarily performed in mice, have found that stem cell-derived RPE cells, photoreceptors, and their precursors can survive long-term in animal models without tumorigenicity or immune rejection. Following transplantation, these cells were able to integrate and mature in vivo, forming synapse-like structures with host retinal cells. Furthermore, transplants in mice were able to rescue visual function at a cellular and behavioral level. These promising preclinical results have led to clinical trials testing cell therapy in numerous diseases, including Stargardt macular dystrophy, age-related macular degeneration, retinitis pigmentosa, and central retinal vein occlusion. These trials have demonstrated the safety of cell therapy and have improved visual function in some patients. Scientific advances in the culturing of retinal organoids and the understanding of cell redifferentiation are informing the development of better stem cell therapies, which hold great potential for restoring vision to patients with retinal dystrophies.},
}

Humans
Animals
*Stem Cell Transplantation/methods
*Retinal Diseases/therapy/surgery
Stem Cells/physiology

@article {pmid42218559,
year = {2026},
author = {Zong, Y and Fan, Q and Huang, L},
title = {Biosimilars of anti-VEGF agents in retinal diseases: a narrative review of regulatory, clinical, and pharmacoeconomic aspects.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00872-9},
pmid = {42218559},
issn = {2056-9920},
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) agents are the cornerstone therapy for retinal vascular diseases including neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. With patent expirations of ranibizumab and aflibercept, biosimilars have emerged as cost-effective alternatives. However, vitreoretinal specialists require consolidated evidence on regulatory standards, clinical equivalence, and practical implementation strategies to guide evidence-based integration of biosimilars into clinical practice.

METHODS: We conducted a narrative review of regulatory documents from the FDA, EMA, and NMPA, as well as Phase III clinical trials, real-world studies, and pharmacoeconomic analyses of approved ophthalmic anti-VEGF biosimilars. Literature searches were performed across PubMed, Embase, and regulatory databases from 2015 to 2025. Studies were included if they reported regulatory approval pathways, clinical efficacy and safety data, interchangeability studies, or pharmacoeconomic evaluations of anti-VEGF biosimilars in retinal diseases.

RESULTS: Regulatory frameworks demonstrate rigorous biosimilarity assessment through comprehensive analytical characterization, preclinical evaluation, and clinical trials. Pivotal Phase III studies confirm therapeutic equivalence of approved biosimilars (including ranibizumab-nuna and aflibercept-abzv) with comparable visual acuity outcomes, safety profiles, and immunogenicity to originator products. Real-world evidence for ranibizumab biosimilars supports comparable outcomes to originators, while evidence for aflibercept biosimilars remains preliminary and warrants continued pharmacovigilance. Pharmacoeconomic analyses demonstrate 20-40% cost reduction compared to originators, offering substantial healthcare savings and improved patient access. Key implementation considerations include extrapolation principles, switching protocols, and clinic workflow integration.

CONCLUSIONS: Although real-world data for aflibercept biosimilars are currently limited, emerging evidence for ranibizumab biosimilars supports comparable outcomes. Approved anti-VEGF biosimilars represent safe, effective, and cost-saving alternatives for retinal diseases. With robust analytical and clinical evidence supporting biosimilarity, vitreoretinal specialists can confidently adopt these agents. Successful integration requires understanding of regulatory science, evidence-based switching protocols, and healthcare system collaborations to maximize patient benefits while maintaining treatment standards. Future research should focus on long-term outcomes, broader implementation studies, and pharmacovigilance monitoring.},
}

@article {pmid42206905,
year = {2026},
author = {Kayembe-Mulumba, B and Delcourt, C and Delyfer, MN},
title = {Controversial Links Between Cardiometabolic Factors and Age-Related Macular Degeneration: Methodological Perspectives for Future Research.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-18},
doi = {10.1080/02713683.2026.2678294},
pmid = {42206905},
issn = {1460-2202},
abstract = {PURPOSE: Epidemiological studies yielded conflicting results regarding the relationship between cardiometabolic factors and age-related macular degeneration (AMD). However, the methodological characteristics of these studies, which may partly explain this controversy, are not currently addressed. This narrative review aimed to examine current evidence between the six most studied cardiometabolic factors and AMD, focusing on identifying key methodological shortcomings and discussing analytical approaches currently available to address them.

METHODS: We conducted a rigorous, nonsystematic literature search using targeted MeSH terms and keywords in MEDLINE (PubMed), EMBASE, Web of Science and Scopus, with no language restrictions, up to June 2025. We identified and reviewed epidemiological (cross-sectional, case-control, cohort) studies reporting original data on the six targeted cardiometabolic factors: blood pressure, antihypertensive medications, lipid levels, lipid-lowering medications, diabetes mellitus and antidiabetic treatments. A quantitative synthesis of studies was conducted to describe their methodological characteristics and reported associations.

RESULTS: Across the 116 reviewed associations, prospective cohorts (41%) and cross-sectional designs (37%) predominated. Most originated from America (35%) and Europe (32%). Lipids (21%) and lipid-lowering agents (20%) were the most frequently studied exposures, while advanced AMD was the predominant outcome (56%). Logistic regression was the main analytic approach (70%), and association conclusions were most often null (42%), followed by increased (36%) and decreased (22%) risk. The most common methodological limitations included cross-sectional study designs, static modeling of dynamic exposures, unaddressed interval censoring, not controlling for confounding by indication, and unstandardized selection of confounders, which are likely to bias the reported associations.

CONCLUSIONS: Future studies should prioritize robust methodological frameworks, including longitudinal designs, survival bias mitigation, standardized and repeated exposure assessments, distinction between AMD subtypes, propensity scores for medications use, and advanced causal inference techniques wherever feasible. Such an effort is foundational to strengthening the validity and reproducibility of findings linking cardiometabolic factors to AMD, thereby improving AMD prevention strategies.},
}

@article {pmid42207296,
year = {2026},
author = {Shaikh, A and Pera, MF},
title = {Cell therapy for age-related macular degeneration.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {37},
number = {1},
pages = {},
pmid = {42207296},
issn = {1432-1777},
mesh = {Humans ; *Macular Degeneration/therapy/pathology/genetics ; Animals ; Retinal Pigment Epithelium/pathology/metabolism ; *Cell- and Tissue-Based Therapy/methods ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. The disease is caused by deterioration of the retinal pigment epithelium (RPE), a tissue that plays critical roles in the support of the photoreceptors. Cell therapies to replace damaged RPE in the non-exudative form of AMD have been under development for several decades. We review the progress of cell therapy to date and highlight some promising future directions for research in this area.},
}

Humans
*Macular Degeneration/therapy/pathology/genetics
Animals
Retinal Pigment Epithelium/pathology/metabolism
*Cell- and Tissue-Based Therapy/methods

@article {pmid42207540,
year = {2026},
author = {Xiong, R and Tan, S and Li, Y and Li, H and Zhu, Z and Chen, Y and He, M and Chen, S and Wang, W},
title = {Pathologic Myopia Globe Shape and Long-Term Prognosis.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.1561},
pmid = {42207540},
issn = {2168-6173},
abstract = {IMPORTANCE: Three-dimensional (3D) eye shape may play a critical role in predicting long-term structural and functional outcomes in high myopia.

OBJECTIVE: To determine whether 3D eye shape subtypes defined by high-resolution magnetic resonance imaging (MRI) predict 15-year structural and functional outcomes in high myopia.

This prospective cohort study involved a subsample of individuals with high myopia (spherical equivalent ≤-6.00 D in both eyes) enrolled in the Zhongshan High Myopia Cohort at a single center in China. Participants underwent biennial ophthalmic examinations over 15 years. Baseline assessments began in August 2011, with biennial follow-ups through September 2025. Data were analyzed from October 2025 through December 2025.

EXPOSURES: Eye shape was classified into the following 6 categories: spheroidal, ellipsoidal, conical, nasally distorted, temporally distorted, and barrel shaped. Spheroidal and ellipsoidal types were defined as nondeformed and the others as deformed.

MAIN OUTCOMES AND MEASURES: The primary outcomes were annual axial elongation rate, rapid elongation (≥0.10 mm/y), macular choroidal thinning (subfoveal choroidal thickness <62 µm), progression of myopic macular degeneration (MMD), incidence of posterior staphyloma, visual impairment (best-corrected visual acuity ≤20/40), and visual field defects.

RESULTS: Of 190 eyes from 95 participants, 152 eyes completed follow-up and were included in the analysis. Of the 152 eyes analyzed, 77 (50.7%) were from female participants, with an overall mean (SD) age of 32.3 (14.1) years. Baseline shapes included spheroidal (83 eyes [54.6%]), nasally distorted (25 [16.4%]), conical (23 [15.1%]), ellipsoidal (11 [7.2%]), temporally distorted (5 [3.3%]), and barrel shaped (5 [3.3%]). Axial elongation followed a morphology-dependent gradient, from slowest in spheroidal eyes (0.045 mm/y) to fastest in nasally distorted eyes (0.095 mm/y). After multivariable adjustment, nasally distorted eyes elongated by 0.050 mm/y (95% CI, 0.020-0.080 mm/y; P = .001) faster and had higher odds of rapid elongation (odds ratio, 5.74; 95% CI, 1.66-19.82; P = .006). Deformed eyes overall had a 7-fold higher risk of macular choroidal thinning (odds ratio, 7.24; 95% CI, 1.77-29.63; P = .006). Nasally distorted and conical eyes showed the greatest risks for both choroidal thinning and MMD progression. For visual field defects, risk was elevated in nasally distorted and conical eyes.

CONCLUSIONS AND RELEVANCE: Findings from this prospective cohort study suggest that 3D eye shape is an important determinant of long-term outcomes in high myopia. Nasally distorted and conical phenotypes conferred the greatest risks, highlighting the potential value of baseline eye shape stratification for personalized management, risk prediction, or early intervention.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN56368396.},
}

@article {pmid42208846,
year = {2026},
author = {Heo, YJ and Bishayee, K and Jhun, JY and Han, SG and Lee, YS and Park, YG and Cho, ML and Park, YS},
title = {Mitochondrial transplantation protects the retinal pigment epithelial cells from the oxidative stress induced by NaIO3.},
journal = {Experimental eye research},
volume = {270},
number = {},
pages = {111090},
doi = {10.1016/j.exer.2026.111090},
pmid = {42208846},
issn = {1096-0007},
abstract = {The retinal pigment epithelium (RPE) is the outermost part of the retina, and it is essential for the photoreceptor survival and function. Oxidative stress, aging, accumulation of lipofuscin, and drusen can lead to retinal degenerative diseases such as age-related macular degeneration (AMD). Those stress conditions increase reactive oxygen species (ROS) levels and oxidative stress, which can induce mitochondrial dysfunction and promote RPE cell death during retinal degeneration. We transplanted mitochondria, isolated from C2C12 cells, into cultured RPE cells, and RPE cell injury was induced by NaIO3 treatment. To evaluate the protective effect of mitochondrial transplantation, Annexin V/PI and cell viability assays were performed to measure the cell survival, and ROS levels were measured by flow cytometry to analyze cellular stress. To understand the underlying protective mechanism of mitochondrial transplantation, we measure expression of the antioxidant genes, mitochondrial fusion/fission markers, and mitophagy makers using qRT-PCR and Western blot methods. Mitochondrial transplantation reduced NaIO3-induced cell death and ROS levels, and antioxidant genes related to the Nrf2 pathway were upregulated, providing a protective effect against retinal damage. In addition, mitochondrial fusion was increased, whereas fission was decreased in the NaIO3 model. Furthermore, mitophagy was increased by mitochondrial transplantation, which could clear damaged mitochondria through a cellular protective pathway. In conclusion, mitochondrial transplantation could protect the RPE cells by maintaining mitochondrial homeostasis and promoting the antioxidant pathway via Nrf2 activation. This study suggests that mitochondrial transplantation could be a potential treatment option for improving AMD progress in the future.},
}

@article {pmid42211220,
year = {2026},
author = {Peng, Y and Liang, LY and Wei, HL and Huang, Q and Yuan, LM and Xie, YY and Tang, QY and Wang, AQ and Li, JM and Guo, QS and Huang, BL},
title = {Fructus lycii mitigates oxidative stress in dry age-related macular degeneration models via Nrf2/ARE pathway.},
journal = {International journal of ophthalmology},
volume = {19},
number = {6},
pages = {1048-1056},
pmid = {42211220},
issn = {2222-3959},
abstract = {AIM: To evaluate the effect of Fructus lycii (FL) aqueous extract on dry age-related macular degeneration (AMD) in mice via the nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling pathway and investigate the protective effect of FL-containing serum on hydrogen peroxide (H2O2)-treated human retinal pigment epithelial cells (ARPE-19) in vitro.

METHODS: In vivo dry AMD mouse model was established by intraperitoneal injection of NaIO3 solution and treated with aqueous extract of FL. The pathological changes of mouse retinal tissues were observed by electron microscopy; the activity of superoxide dismutase (SOD) and catalase (CAT) in mouse serum was detected by colorimetric method. In vitro dry AMD model was established by H2O2 induction of ARPE-19 cells and treated with FL-containing serum. Methylthiazolyldiphenyl-tetrazolium bromide assay and scratch assay were performed to detect cell activity and proliferation ability. Expression of Nrf2, heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic subunit (GCLC) in retinal tissues and ARPE-19 cells were detected by Western blot and quantitative real-time polymerase chain reaction (Q-PCR).

RESULTS: The in vivo study revealed severe deposits under the retinal pigment epithelium and thickened Bruch's membrane in dry AMD mice. However, aqueous extract of FL reduced the formation of deposits and decreased the thickness of Bruch's membrane. SOD and CAT activities were significantly reduced in the serum of dry AMD mice, and aqueous extract of FL upregulated SOD and CAT activities. In addition, gene and protein expression of Nrf2, HO-1, and GCLC were significantly downregulated in dry AMD mice, but significantly upregulated by FL aqueous extract treatment. In vitro studies showed that H2O2 inhibited the activity and proliferative capacity of ARPE-19 cells and downregulated the protein and gene expression of Nrf2, HO-1 and GCLC. However, in H2O2-treated ARPE-19 cells, FL-containing serum not only increased cell activity and proliferative capacity, but also upregulated protein and gene expression of Nrf2, HO-1, and GCLC.

CONCLUSION: FL reduces oxidative stress in an animal model of dry AMD through the Nrf2/ARE signaling pathway and has a protective effect on dry AMD in vitro and in vivo, providing new insights into the therapeutic use of FL for dry AMD.},
}

@article {pmid42211726,
year = {2026},
author = {Berni, A and Shen, M and Liu, J and Kastner, JD and El-Mulki, OS and Beqiri, S and Herrera, G and Trivizki, O and Waheed, NK and Usner, DW and Levy, B and O'Brien, R and Gregori, G and Rosenfeld, PJ},
title = {Novel Clinical Trial Designs for Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {6},
pages = {101179},
pmid = {42211726},
issn = {2666-9145},
abstract = {PURPOSE: To develop and model clinical trial designs for intermediate age-related macular degeneration (iAMD) using OCT-based structural biomarkers to define inclusion criteria and estimate sample size requirements for detecting treatment effects over 2 years.

DESIGN: Retrospective study of a prospectively acquired swept-source OCT cohort.

SUBJECTS: Patients with iAMD enrolled in a prospective natural history imaging study.

METHODS: Two clinical trial designs were modeled. The first included eyes with drusen volume (DV) ≥0.20 mm[3] and any hyperreflective foci (HRF). The second included eyes with an area of HRF ≥0.07 mm[2], regardless of DV. Eyes were followed from the time of eligibility and monitored for the onset and growth of large hypertransmission defects (hyperTDs). Power and sample size simulations were performed based on the expected treatment effects.

MAIN OUTCOME MEASURES: Annual square root growth rates of large hyperTDs and incidence of new large hyperTDs over 2 years.

RESULTS: In 76 eyes with DV ≥0.20 mm[3] and HRF, the mean annual growth rate of large hyperTDs was 0.153 mm/year (standard deviation [SD] = 0.188), and 35.5% of these iAMD eyes developed hyperTDs by 2 years. In the 79 eyes with HRF area ≥0.07 mm[2], the mean annual growth rate was 0.161 mm/year (SD = 0.172), and 40.5% developed hyperTD by 2 years. With a 2-sided alpha of 0.1, a 50% reduction in the growth rate could be detected with 80% power using ≥89 eyes per arm in the first group and ≥64 eyes per arm in the second group.

CONCLUSIONS: The growth rate of large hyperTDs is a continuous and reproducible structural endpoint for iAMD trials, influenced by both lesion onset and progression. Drusen volume or the area of HRF serves as high-risk biomarkers for enrolling iAMD eyes. This design allows for a study duration of 1-2 years with no more than 100 subjects per arm.

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

@article {pmid42212360,
year = {2026},
author = {Zhang, W and Chen, J and Zhong, J},
title = {Regulatory mechanisms and therapeutic potential of N6-methyladenosine modification in retinal diseases (Review).},
journal = {Molecular medicine reports},
volume = {34},
number = {1},
pages = {},
doi = {10.3892/mmr.2026.13923},
pmid = {42212360},
issn = {1791-3004},
mesh = {Humans ; *Adenosine/analogs & derivatives/metabolism/genetics ; RNA Methylation ; *Retinal Diseases/metabolism/genetics/drug therapy/therapy/pathology ; Animals ; Epitranscriptome ; Methyltransferases/metabolism/genetics ; RNA, Messenger/metabolism/genetics ; Gene Expression Regulation ; },
abstract = {N6‑Methyladenosine (m6A) modification, the most abundant internal chemical modification in eukaryotic messenger RNA, plays a central role in gene expression by dynamically regulating RNA metabolism. The present review systematically summarizes the regulatory mechanisms and pathological significance of m6A modification in major retinal diseases, including diabetic retinopathy, age‑related macular degeneration, retinoblastoma, uveitis and retinitis pigmentosa. Studies indicate that m6A methyltransferases (METTL3), demethylases (FTO and ALKBH5) and reader proteins (the YTH domain‑containing family of proteins) participate in pathological processes such as angiogenesis, inflammatory responses, pyroptosis and photoreceptor degeneration by modulating the stability, translation efficiency and degradation of key gene mRNAs. Furthermore, this review explores the therapeutic potential of targeting m6A‑modifying enzymes (for example, small‑molecule inhibitors STM2457 and FB23‑2) and highlights challenges in tissue specificity, delivery systems and clinical translation. Future research should integrate multi‑omics technologies and precision intervention strategies to advance the application of m6A modification in the diagnosis and treatment of retinal diseases.},
}

Humans
*Adenosine/analogs & derivatives/metabolism/genetics
RNA Methylation
*Retinal Diseases/metabolism/genetics/drug therapy/therapy/pathology
Animals
Epitranscriptome
Methyltransferases/metabolism/genetics
RNA, Messenger/metabolism/genetics
Gene Expression Regulation

@article {pmid42212881,
year = {2026},
author = {Ansari, G and Oertli, J and Mächler, L and Lipsky, T and Jeffrey, BG and Cukras, CA and Feltgen, N and Klaver, CCW and Pfau, K and Pfau, M},
title = {Parafoveal Dark Adaptation in Early and Intermediate Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {74},
doi = {10.1167/iovs.67.5.74},
pmid = {42212881},
issn = {1552-5783},
mesh = {Humans ; *Dark Adaptation/physiology ; *Macular Degeneration/physiopathology/diagnosis ; Female ; Cross-Sectional Studies ; *Fovea Centralis/physiopathology ; Aged ; Male ; *Retinal Rod Photoreceptor Cells/physiology ; ROC Curve ; Middle Aged ; Aged, 80 and over ; },
abstract = {PURPOSE: Rod-mediated dark adaptation delays are among the earliest functional abnormalities in age-related macular degeneration (AMD), preceding photoreceptor loss. This study evaluated whether parafoveal fundus-tracked dark adaptometry at 2 degrees detects earlier rod dysfunction than mid-macular loci (4 degrees and 6 degrees) and assessed the diagnostic performance of dynamic and steady-state parameters across eccentricities.

METHODS: In this cross-sectional study, 35 patients with predominantly early/intermediate AMD and 35 healthy volunteers across a broad range of ages underwent fundus-controlled dark adaptometry (S-MAIA-2; iCare/CenterVue) and multimodal imaging. After standardized bleaching, Goldmann III sized (0.43 degrees) cyan stimuli were presented 2 degrees, 4 degrees, and 6 degrees temporal to the fovea. Dark-adaptation curves were modeled to derive rod intercept time (RIT), final (rod) threshold (FT), and cone threshold (CT), each compared with normative data. Diagnostic accuracy was quantified using covariate-adjusted receiver operating characteristic (ROC) analyses, to account for age.

RESULTS: Among 70 analyzed eyes, RIT was abnormal in 86% of AMD eyes at 2 degrees, 69% at 4 degrees, and 60% at 6 degrees, whereas FT and CT were less frequently abnormal (29% to 51% and 17% to 26%, respectively). Median RIT at 2 degrees reached 60 minutes in the AMD cohort, indicating absence of rod function within the test duration in many eyes. RIT achieved the highest diagnostic accuracy, with covariate-adjusted area under the curve (AUC) values of 0.91 (95% credible intervals [CrI] = 0.80-0.97) at 2 degrees, 0.88 (95% CrI = 0.77-0.96) at 4 degrees, and 0.87 (95% CrI = 0.76-0.95) at 6 degrees.

CONCLUSIONS: Fundus-tracked dark adaptometry enables spatially precise assessment of parafoveal rod recovery. Parafoveal RIT prolongation represents the earliest and most frequent functional abnormality in AMD and demonstrates excellent diagnostic performance, supporting its potential as a sensitive functional biomarker for early disease and therapeutic trials.},
}

Humans
*Dark Adaptation/physiology
*Macular Degeneration/physiopathology/diagnosis
Female
Cross-Sectional Studies
*Fovea Centralis/physiopathology
Aged
Male
*Retinal Rod Photoreceptor Cells/physiology
ROC Curve
Middle Aged
Aged, 80 and over

@article {pmid42212887,
year = {2026},
author = {Tsai, CY and Weng, CH and Tsai, CY and Sheen, YJ and Chen, JP and Chen, HM and Wang, IJ and Chou, CC},
title = {Association Between PCSK9 Inhibitor Use and Risk of Age-Related Macular Degeneration.},
journal = {Translational vision science & technology},
volume = {15},
number = {5},
pages = {29},
doi = {10.1167/tvst.15.5.29},
pmid = {42212887},
issn = {2164-2591},
mesh = {Humans ; Male ; *Macular Degeneration/epidemiology/prevention & control ; Retrospective Studies ; Middle Aged ; *PCSK9 Inhibitors ; Aged ; Female ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Risk Factors ; Hyperlipidemias/drug therapy ; Incidence ; Proprotein Convertase 9 ; *Anticholesteremic Agents/therapeutic use ; Propensity Score ; Proportional Hazards Models ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) has been linked to systemic lipid imbalance, vascular dysfunction, and inflammation. The ocular effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, have not been established. We evaluated whether PCSK9 inhibitor use is associated with reduced AMD risk compared with statin therapy.

METHODS: We conducted a retrospective propensity score-matched cohort study using the TriNetX multinational electronic health record database (2015-2024) with up to 5 years of follow-up. Adults aged ≥50 years with hyperlipidemia but no prior retinal disease were included. Participants were assigned to PCSK9 inhibitor or statin therapy groups and matched 1:1 based on demographic, clinical, and laboratory variables. Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs), and Kaplan-Meier analyses illustrated cumulative AMD incidence.

RESULTS: Among 56,660 matched participants, PCSK9 inhibitor use was associated with a significantly lower risk of AMD compared with statin therapy (HR, 0.82; 95% CI, 0.73-0.90). The association remained robust in sensitivity analyses across different follow-up intervals. Stratified analyses showed consistent findings in both age groups (50-75 and ≥75 years), male participants, those without type 2 diabetes, nonobese individuals, and those with <2 years of hyperlipidemia duration.

CONCLUSIONS: In this large real-world cohort, PCSK9 inhibitor use was associated with a lower AMD risk compared with statin monotherapy. Prospective studies are needed to confirm causality.

TRANSLATIONAL RELEVANCE: This study supports further evaluation of PCSK9 inhibition as a potential strategy to modify AMD risk.},
}

Humans
Male
*Macular Degeneration/epidemiology/prevention & control
Retrospective Studies
Middle Aged
*PCSK9 Inhibitors
Aged
Female
Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
Risk Factors
Hyperlipidemias/drug therapy
Incidence
Proprotein Convertase 9
*Anticholesteremic Agents/therapeutic use
Propensity Score
Proportional Hazards Models

@article {pmid42213134,
year = {2026},
author = {Cinque, F and Brink, SCAT and Shahabi, M and de Breuk, A and Heesterbeek, TJ and Klaver, CCW and Hoyng, CB and Lechanteur, YTE},
title = {Clinical course of non-exudative macular neovascularisations in sustained unilateral neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42213134},
issn = {1435-702X},
abstract = {PURPOSE: To assess the risk of conversion of non-exudative macular neovascularisations (NEMNV) in relation to disease history in sustained unilateral neovascular age-related macular degeneration (AMD).

METHODS: This exploratory case-only cohort study included six-monthly visits. Fellow-eye NEMNV were identified using fluorescein and indocyanine green angiography. Patients were stratified by time since first-eye exudation: < 5 years (G1) or ≥ 5 years (G2). The primary outcome was the cumulative annual conversion rate of NEMNV, expressed as conversion rate ratios (CRR) with 95% confidence intervals (CI). Secondary outcomes were independent grading of foveal involvement, core vessel, central core vessel, round shape, sharp borders, and lesion growth.

RESULTS: A total of 134 patients (65.7% female) were included. Mean age at baseline was 74.2 years (SD 8.0). Median time since first-eye exudation was 2.9 years (IQR 1.0-6.3). Patients in G2 had an earlier age at first-eye exudation (66.0 [9.1] years) than G1 (72.7 [7.8]; P < .001). Seven NEMNV lesions were identified (G1:2, G2:5). Cumulative conversion rates were 22.1% overall, 14.3% in G1, and 27.1% in G2. CRR were 2.3 (95% CI 0.6-6.2), 1.3 (95% CI 0.0 - 7.8), and 4.0 (95% CI 0.7 - 16.8). All but one NEMNV showed growth.

CONCLUSION: In this limited sample, most NEMNV show growth time regardless of conversion to exudative AMD and appear at a higher risk of conversion. The rate of conversion varies with the age of onset of first-eye exudation. Evaluating potential predictive signs of conversion may benefit from incorporating disease history with vascular features.},
}

@article {pmid42213331,
year = {2026},
author = {La Torre, G and D'Urso, P},
title = {Evaluating synergistic effects among multiple factors in disease causation: a new approach using a generalized synergy index.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {42213331},
issn = {1573-7284},
abstract = {The methodological objective of the present study is to extend Rothman's additive interaction framework from two factors to three or more factors considered simultaneously, while preserving its original causal interpretation and operational simplicity. we propose a generalized Synergy Index (Sp) that retains the additive logic of Rothman's original formulation while extending it to an arbitrary number of dichotomous factors. For the analysis we used a database of a previous work in which the synergistic factor was calculated for each couples of two factors (alcohol, tobacco smoke and other risk factors) for age-related macular degeneration. The proposed three-factor Sp is sensitive to the underlying structure of the risk factors considered. When a strong susceptibility component such as family history is included, the combined exposure exhibits clear super-additive behavior (Sp = 1.783). Conversely, when hypercholesterolemia replaces family history, the joint effect remains substantial but does not exceed additivity (Sp = 0.756). The generalized multi-factor Synergy Index represents a valuable conceptual and analytical tool for investigating higher-order interactions. It is particularly well suited for the study of complex diseases, where multiple exposures co-occur and interact. It enables the identification of exposure constellations characterized by true superadditivity, with potential implications for etiological research, risk stratification, and targeted prevention strategies.},
}

@article {pmid42201956,
year = {2026},
author = {Ly, K and Bhuckory, MB and Pham-Howard, D and Kochnev Goldstein, A and Jensen, N and Palanker, D},
title = {Residual photoreceptors affect the response of a degenerate retina to electrical stimulation.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {22},
pages = {e2537064123},
doi = {10.1073/pnas.2537064123},
pmid = {42201956},
issn = {1091-6490},
support = {R01-EY- 035227//HHS | NIH (NIH)/ ; P30-EY-026877//HHS | NIH (NIH)/ ; W81XWH-2210933//U.S. Department of Defense (DOD)/ ; FA9550-19-1-0402//DOD | AF | AMC | AFRL | Air Force Office of Scientific Research (AFOSR)/ ; },
mesh = {Animals ; *Electric Stimulation ; Rats, Long-Evans ; *Retinal Degeneration/physiopathology/therapy ; Rats ; Evoked Potentials, Visual/physiology ; *Photoreceptor Cells, Vertebrate/physiology ; *Retina/physiopathology ; Visual Prosthesis ; Retinal Bipolar Cells ; },
abstract = {Photovoltaic subretinal prosthesis can restore central vision in patients blinded by age-related macular degeneration with letter acuity matching its 100 µm pixel size. Improving resolution requires smaller pixels, but to still reach the target neurons, electric field should be less confined. However, wide-spreading field may engage adjacent photoreceptors and alter the visual perception. We studied the effects of residual photoreceptors on retinal responses to electrical stimulation using monopolar and bipolar photovoltaic arrays implanted subretinally in Long Evans rats with local photoreceptor loss, and compared that to RCS rats lacking all photoreceptors. Patterned retinal activation (880 nm, 0.5 to 10 ms) was assessed using visually evoked potentials under scotopic and photopic conditions, with and without the intravitreal injection of neurotransmitter blockers. Results were analyzed using a computational model of photoreceptor activation by various electric field configurations. We observed two mechanisms of photoreceptors engagement in electrical activation of the degenerate retina: 1) Dark-adapted photoreceptors near the implant can be simulated directly by a negative electric potential of the common return electrode along the edge of the array. 2) Light-adapted photoreceptors can reduce the stimulation threshold of bipolar cells within about 100 mm from the implant's edge. Both effects may lead to reduced perceptual uniformity. Bipolar pixels with local return electrodes generate better confined electric fields than monopolar arrays and thus are less affected by the nearby photoreceptors. However, even such implants should be placed a few hundred micrometers from the edge of scotoma to minimize the unintended percepts.},
}

Animals
*Electric Stimulation
Rats, Long-Evans
*Retinal Degeneration/physiopathology/therapy
Rats
Evoked Potentials, Visual/physiology
*Photoreceptor Cells, Vertebrate/physiology
*Retina/physiopathology
Visual Prosthesis
Retinal Bipolar Cells

@article {pmid42202045,
year = {2026},
author = {Zhang, J and Chen, L and Zhu, X and Cai, Y and Wei, S and Zhou, X and Shi, Y and Liu, C and Huang, C and Bi, S and Wu, F and Zhou, X and Hong, J and Wang, Y},
title = {Coordinated regulation using small-molecule drugs enables controlled therapeutic genome editing and enhanced genomic precision in situ.},
journal = {Science translational medicine},
volume = {18},
number = {851},
pages = {eadx7857},
doi = {10.1126/scitranslmed.adx7857},
pmid = {42202045},
issn = {1946-6242},
mesh = {Humans ; Animals ; *Gene Editing/methods ; CRISPR-Cas Systems/genetics ; Mice ; *Genomics ; Dependovirus/genetics ; },
abstract = {Achieving precise temporal control over genome editing is essential for safety but remains a challenge, especially when using small-molecule drugs as external regulators over systems like clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated systems). Consequently, controlled therapeutic in situ editing that maintains both precision and efficacy has yet to be demonstrated. Here, we report the PRINCE system, in which nuclease proteins and guide RNAs are both inducible, to deliver programmable nucleases under control more effectively. PRINCE demonstrated temporal precision in human cell cultures over a 2-year period, even after stable genomic integration. The design principles of PRINCE were broadly applicable from CRISPR-Cas9 to a prime editor and also compact programmable nucleases, and the latter platform was named "Little Prince." Upon administration of drug inducers, Little Prince, delivered in a single adeno-associated virus vector in situ to humanized mouse models, ameliorated pathological phenotypes of hypercholesterolemia (average reductions of 45 and 47% in serum total cholesterol and low-density lipoprotein cholesterol, respectively) and neovascular age-related macular degeneration, with significantly reduced lesion size and leakage (P < 0.0001). Last, we demonstrated a consistent and marked reduction in off-target activity across the PRINCE and Little Prince systems in comparison with constitutive editors, with fewer off-target sites and substantially lower editing frequencies, irrespective of nuclease type, delivery method, or genomic target. These results position PRINCE and Little Prince as controlled genome editing platforms with potential for in vivo, particularly in situ, therapeutic applications.},
}

Humans
Animals
*Gene Editing/methods
CRISPR-Cas Systems/genetics
Mice
*Genomics
Dependovirus/genetics

@article {pmid42203079,
year = {2026},
author = {Koh, TY and Cho, WR and Jeon, HY and Moon, CH and Yoon, JS and Kim, M and Ha, KS},
title = {Sustained human C-peptide protects against retinal neurodegeneration via PEDF restoration and oxidative stress inhibition in a mouse model of age-related macular degeneration.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.05.327},
pmid = {42203079},
issn = {1873-4596},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. The molecular events that initiate retinal degeneration in dry AMD remain incompletely understood, and effective therapeutic options are limited. Here, we investigated the therapeutic potential of K9-C-peptide against sodium iodate (NaIO3)-induced retinal neurodegeneration and explored its underlying molecular mechanisms. K9-C-peptide markedly attenuated NaIO3-induced retinal apoptosis, thinning, and structural disruption. These protective effects were accompanied by significant suppression of ROS generation, decreased expression of pro-inflammatory cytokines, and inhibition of reactive gliosis. Mechanistically, K9-C-peptide restored NaIO3-induced downregulation of pigment epithelium-derived factor (PEDF). Consistently, intravitreal administration of hydrogel-formulated PEDF similarly reduced oxidative stress and retinal degeneration, supporting a central role for PEDF in mediating the protective effects of K9-C-peptide. Both K9-C-peptide and PEDF improved impaired axonal transport, further confirming their neuroprotective efficacy. Notably, sustained intraocular delivery of human C-peptide or PEDF conferred robust protection against NaIO3-induced retinal neurodegeneration for at least three weeks following a single administration. These findings suggest that K9-C-peptide may serve as a long-acting therapeutic candidate that targets early oxidative and inflammatory events, potentially through PEDF restoration, in NaIO3-induced retinal degeneration. This study provides mechanistic insight into the antioxidative and anti-inflammatory actions of C-peptide-based therapy in dry AMD-like pathology.},
}

@article {pmid42205117,
year = {2026},
author = {García-Otero, X and Cuartero-Martínez, A and Fernández-Robredo, P and Antas, SG and Gómez-Lado, N and Otero-Espinar, FJ and Hernández, M and Bezunartea, J and García-Layana, A and Recalde, S and Aguiar, P and Fernández-Ferreiro, A},
title = {Intravitreal faricimab pharmacokinetics assessed by PET imaging in a neovascular Age-related Macular Degeneration rat model.},
journal = {International journal of pharmaceutics: X},
volume = {11},
number = {},
pages = {100567},
pmid = {42205117},
issn = {2590-1567},
abstract = {Age-related Macular Degeneration (AMD) is the leading cause of blindness in the elderly, with its neovascular form characterised by abnormal vessel growth. Current anti-VEGF therapies require frequent intravitreal injections and show variable efficacy. Faricimab, a novel bispecific antibody targeting VEGF-A and ANG-2, offers a dual mechanism with the potential for enhanced efficacy and extended dosing intervals. This study aimed to characterise the intravitreal pharmacokinetics, biodistribution, and ocular localization of faricimab in a rat model of laser-induced choroidal neovascularization (CNV) using non-invasive molecular imaging. Faricimab was conjugated with DFO and radiolabelled with zirconium-89 ([[89]Zr]Zr-DFO-faricimab), maintaining functional binding to VEGF-A and ANG-2. Following intravitreal injection, pharmacokinetics was assessed by PET/CT, blood sampling, and autoradiography, alongside structural retinal evaluation by OCT. Both healthy and CNV-induced rats demonstrated biphasic ocular clearance with similar half-lives, obtaining no significant differences (Control AUC0-∞ = 5587.3 ± 1419.3%·hour and AMD AUC0-∞ = 4079.1 ± 1178.6%·hour). Autoradiography confirmed predominant retention in the posterior segment, with AMD eyes showing higher early accumulation, suggesting altered diffusion, and increased retinal binding. Whole-body biodistribution revealed systemic uptake primarily in the liver and spleen, consistent with antibody catabolism. This work represents the first study to report pharmacokinetic data of faricimab as well as its intraocular distribution in an AMD model. Our findings support its therapeutic potential and highlight PET imaging as a powerful non-invasive tool for longitudinal ocular pharmacokinetic studies.},
}

@article {pmid42190944,
year = {2026},
author = {Demirel, R and Irgat, SG and Bike, HI},
title = {Subretinal fluid resolution in the fellow eye after unilateral aflibercept injection in bilateral neovascular age-related macular degeneration: coincidence or systemic effect?.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {},
number = {},
pages = {502585},
doi = {10.1016/j.oftale.2026.502585},
pmid = {42190944},
issn = {2173-5794},
abstract = {We report a case of bilateral neovascular age-related macular degeneration (nAMD) in which a unilateral aflibercept injection led to complete resolution of subretinal fluid (SRF) in the untreated fellow eye. A 63-year-old woman undergoing treat-and-extend therapy for the right eye developed new SRF in the left eye, which maintained good vision (best-corrected visual acuity, 0.8; defined as ≥0.5 Snellen or ≤0.3 logMAR). To avoid injection-related risks in a high-vision eye, only the right eye was treated. Three weeks later, optical coherence tomography demonstrated complete SRF resolution in the left eye, which persisted for 8 weeks before recurrence. This case raises the possibility that systemic absorption of anti-vascular endothelial growth factor (anti-VEGF) may temporarily suppress choroidal neovascularisation activity in the fellow eye. However, this single observation cannot guide clinical practice and requires prospective validation.},
}

@article {pmid42190948,
year = {2026},
author = {Kavyasree, PKV and Jayadevan, K and Abdullah, M and Therayil, A},
title = {Redox-inflammation pathways in ocular disease: targets for nutritional modulation.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {},
number = {},
pages = {502581},
doi = {10.1016/j.oftale.2026.502581},
pmid = {42190948},
issn = {2173-5794},
abstract = {Visual impairment remains a major global health burden caused by diverse ocular diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, and ocular surface disorders. Despite differing etiologies, growing evidence identifies oxidative stress and chronic inflammation as a shared pathogenic axis affecting both anterior and posterior ocular segments. High metabolic demand, sustained light exposure, dense mitochondrial content, and limited antioxidant defences render ocular tissues particularly susceptible to redox imbalance. Excess reactive oxygen species induce cellular injury and activate redox-sensitive inflammatory signalling, promoting neurodegeneration, microvascular dysfunction, immune-mediated damage, and progressive vision loss. This review summarises key mechanisms underlying redox-inflammatory crosstalk in ocular tissues, highlighting mitochondrial dysfunction, Nrf2-Keap1 antioxidant responses, NF-κB-driven inflammation, and MAPK and PI3K-Akt signalling as central molecular integrators. Tissue-specific responses in the retina, retinal pigment epithelium, trabecular meshwork, uveal tract, and ocular surface demonstrate how shared mechanisms generate distinct disease phenotypes. The modulatory potential of bioactive nutrients, including omega-3 fatty acids, carotenoids, and polyphenols, is critically discussed. Although preclinical evidence is strong, clinical outcomes remain variable, underscoring the need for precision nutrition strategies and mechanism-based clinical trial design.},
}

@article {pmid42191674,
year = {2026},
author = {Sampson, J and Segrè, AV and Bujakowska, KM and Clark, SJ and Bishop, PN and Haynes, S and Baralle, D and Al-Deek, J and Holden, S and Anderson, B and Hayes, A and Kemal, RA and Thomas, HB and O'Keefe, RT and Banka, S and Black, GC and Sergouniotis, PI and Ellingford, JM},
title = {Paired DNA and RNA sequencing uncovers common and rare variation regulating human retinal gene expression.},
journal = {Nature communications},
volume = {17},
number = {1},
pages = {},
pmid = {42191674},
issn = {2041-1723},
mesh = {Humans ; *Retina/metabolism ; Quantitative Trait Loci/genetics ; *Gene Expression Regulation ; Retinal Pigment Epithelium/metabolism ; *Genetic Variation ; Sequence Analysis, RNA ; Polymorphism, Single Nucleotide ; DNA Copy Number Variations ; Whole Genome Sequencing ; },
abstract = {Genetic disorders impacting vision affect millions of individuals worldwide, including age-related macular degeneration (common) and inherited retinal disorders (rare). There is an incomplete understanding of the impact of genetic variation on gene expression in the human retina and its role in genetic disorders. Through the generation of whole genome sequencing and bulk RNA-sequencing of neurosensory retina and retinal pigment epithelium from 201 post-mortem eyes, we uncover common and rare genomic variants shaping retinal expression profiles. This includes 1,483,595 significant cis-expression quantitative trait loci impacting 9,959 and 3,699 genes in neurosensory retina and retinal pigment epithelium, respectively, with associated genomic variants enriched to cis-candidate regulatory elements and notable shared eGenes between both tissues. We also detect 1051 expression outliers and prioritise 299 rare non-coding single-nucleotide, structural variants or copy number variants as plausible drivers for 28% of outlier events. This study increases understanding of gene expression regulation in the human retina.},
}

Humans
*Retina/metabolism
Quantitative Trait Loci/genetics
*Gene Expression Regulation
Retinal Pigment Epithelium/metabolism
*Genetic Variation
Sequence Analysis, RNA
Polymorphism, Single Nucleotide
DNA Copy Number Variations
Whole Genome Sequencing

@article {pmid42193268,
year = {2026},
author = {Gopi, S and Prodanoff, GT and Passaglia, CL and Kindy, MS and Sutariya, V and Halade, GV and Lewin, AS and Biswal, MR},
title = {Non-Erythropoietic EPO (EPO-R76E) Protects RPE Cells from Ferroptosis by Modulating the Labile Iron Pool and NRF2-GPX4 Axis.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {5},
pages = {},
doi = {10.3390/antiox15050647},
pmid = {42193268},
issn = {2076-3921},
support = {1R00EY027013-04/NH/NIH HHS/United States ; 1R01EY033415-03/NH/NIH HHS/United States ; },
abstract = {Retinal pigment epithelium (RPE) degeneration remains a formidable challenge in dry age-related macular degeneration (AMD) research, primarily due to the toxic interplay between iron overload and ferroptosis. We investigated whether EPO-R76E, a non-erythropoietic modified variant of erythropoietin, could effectively interrupt this destructive cycle. Using ARPE-19 cells challenged with ferric ammonium citrate (FAC) to model iron-induced toxicity, we show that EPO-R76E confers protection against ferroptosis. Our results demonstrate that this variant significantly reduces the intracellular labile iron pool, directly quenching the lipid peroxidation that drives ferroptotic cell death. This resilience is fueled by a robust upregulation of Glutathione Peroxidase 4 (GPX4) and the broad transcriptional activation of the NRF2 (Nuclear factor erythroid 2-related factor 2) NRF2 antioxidant axis. Furthermore, we found that EPO-R76E enhances autophagic flux, ensuring that cells maintain essential proteostasis and "housekeeping" functions even under metabolic crisis. By integrating iron sequestration with reinforced antioxidant signaling and cellular clearing mechanisms, EPO-R76E stands out as a potent candidate for preserving RPE health. These findings uncover a novel molecular framework for protecting the retina against iron-mediated injury, positioning EPO-R76E as a versatile and targeted gene-based therapeutic for addressing the fundamental causes of retinal degeneration.},
}

@article {pmid42193449,
year = {2026},
author = {Xiong, C and Zhou, S and Hu, Y and Xu, X},
title = {Exploring Biomarkers and Mechanisms of Action of Adaptive Immune Response in Age-Related Macular Degeneration Based on Transcriptomics.},
journal = {Biomedicines},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/biomedicines14051123},
pmid = {42193449},
issn = {2227-9059},
support = {82374214//National Natural Science Foundation of China/ ; },
abstract = {Background: Age-related macular degeneration (AMD) is a common retinal degenerative disease linked to adaptive immune response dysregulation. This study aimed to identify shared immune-related biomarkers and explore their underlying mechanisms. Methods: GSE29801 and GSE135092 served as training and validation sets. Adaptive immune response-related genes (AIR-RGs) from MSigDB were intersected with AMD-related differentially expressed genes (DEGs) to identify candidate genes. Machine learning algorithms were applied to screen biomarkers, validated in datasets and a mouse model of choroidal neovascularization by qPCR. A nomogram was constructed and assessed. GSEA and immune infiltration analyses explored mechanisms and immune microenvironment associations. Results: A total of 148 DEGs were identified, yielding 15 candidate genes after intersection with AIR-RGs. Machine learning identified C3 and HLA-DOA as potential biomarkers, with their differential expression validated across datasets. A nomogram based on these biomarkers demonstrated good predictive performance for AMD pathology (AUC = 0.795). Biomarkers were associated with some immune-inflammatory pathways. Significant differences in immune cell infiltration were observed between AMD and control groups, with biomarkers positively correlated with differentially infiltrated immune cells, such as natural killer cells. Conclusions: The identification of the established biomarker C3 serves as a proof-of-principle for the analytical approach, rather than a novel discovery, thereby validating the model's capacity to uncover other critical immune targets. Consequently, C3 and HLA-DOA serve as potential biomarkers for AMD, significantly correlated with disease progression via immune pathways and offering insights for immune-based therapeutic strategies.},
}

@article {pmid42193986,
year = {2026},
author = {Bhattacharya, S and Ang, C and Soucy, M and Tsang, SH and Chaum, E},
title = {Prominin-1 and Retinal Degenerative Disorders: Expanding the Biology from Photoreceptors to the Retinal Pigment Epithelium.},
journal = {Biomolecules},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/biom16050635},
pmid = {42193986},
issn = {2218-273X},
support = {GF02527//International Retinal Research Foundation/ ; GR020592//Carl Marshall and Mildred Almen Reeves Foundation/ ; Unrestricted Research Grant to the Vanderbilt Eye Institute//Research to Prevent Blindness/ ; Margy Ann and J Donald M. Gass Chair Endowment//Vanderbilt University Medical Center/ ; R24EY028758//Research to Prevent Blindness/ ; R24EY027285//Research to Prevent Blindness/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/pathology ; Animals ; *AC133 Antigen/metabolism/genetics ; *Retinal Degeneration/metabolism/pathology/genetics ; Autophagy ; },
abstract = {Prominin-1 (Prom1/CD133) has long been recognized as a structural determinant of photoreceptor outer segment (OS) morphogenesis, yet rapidly accumulating evidence extends its role to retinal pigment epithelium (RPE) homeostasis, encompassing autophagy-lysosomal flux, outer segment phagocytosis, mitochondrial function, and regulation of inflammatory stress. This review synthesizes mechanistic and transcriptomic insights that position PROM1 as a central regulator of photoreceptor and RPE integrity, reframing Prom1 disease as a multi-compartment retinal disorder relevant to both inherited retinal dystrophies (IRDs) and atrophic age-related macular degeneration (aAMD). We develop a dual-axis conceptual model in which Prom1 dysfunction can initiate pathology in either the photoreceptors (OS morphogenesis failure) or the RPE, including impaired autophagic flux, lysosomal activity, defective phagocytosis, and Epithelial-Mesenchymal Transition (EMT)-like de-differentiation, with secondary cross-compartmental degeneration. Clinically, autosomal-dominant missense variants associate with macular or cone-rod dystrophy, whereas biallelic truncating/splice-site mutations drive early-onset rod-cone disease and panretinal/RPE atrophy, illustrating genotype-phenotype diversity. By integrating recent high-resolution transcriptomic data from Prom1-deficient RPE cells with long-standing insights into photoreceptor biology, we highlight converging pathways of degeneration that challenge a photoreceptor-centric view and unify disparate phenotypes within a single molecular framework. These insights broaden the therapeutic landscape, advancing gene augmentation and pathway-targeted strategies to preserve RPE integrity, sustain photoreceptor function, and modify disease course in PROM1-associated IRDs and atrophic AMD.},
}

Humans
*Retinal Pigment Epithelium/metabolism/pathology
Animals
*AC133 Antigen/metabolism/genetics
*Retinal Degeneration/metabolism/pathology/genetics
Autophagy

@article {pmid42194525,
year = {2026},
author = {Szymańska, K and Sałasińska, K and Młynarczyk, A and Miszczak, J and Dmoch, W and Maciejewicz, P},
title = {The Gut-Eye Axis and Microbiome in Ophthalmic Diseases: A Narrative Review.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103563},
pmid = {42194525},
issn = {2077-0383},
abstract = {The gut microbiome regulates host metabolism, barrier integrity, and immune homeostasis through microbe-host signaling and bioactive metabolites. Growing evidence suggests that dysbiosis may also influence ocular immune privilege and blood-retinal barrier stability, supporting the emerging concept of the gut-eye axis. This narrative review aimed to integrate retinal, uveal, and ocular surface disorders within a shared functional framework, with emphasis on recurring mechanistic pathways and their translational relevance rather than on single diseases or isolated taxonomic findings. The review was based on a literature search of PubMed and Scopus and primarily included English-language studies published between 2015 and 2025, with earlier seminal papers included when needed. The search was last updated in March 2026, and 101 sources were included in the final narrative synthesis. Across age-related macular degeneration, diabetic retinopathy, glaucoma, uveitis, dry eye disease, and Sjögren's syndrome, the most consistent microbiome-related signals were functional rather than taxonomic. Recurrent mechanistic themes included Th17/Treg immune programming, barrier dysfunction with microbial product translocation, and systemic metabolite signaling, particularly involving short-chain fatty acids, bile acid receptor pathways, and tryptophan-derived metabolites. Age-related macular degeneration and diabetic retinopathy showed the strongest multi-layered support, whereas uveitis provided a compelling immune-centered biological model that remains limited by treatment-related confounding in human studies. In glaucoma and ocular surface disease, evidence supports biological plausibility, especially in relation to neuroinflammation, mucosal immune dysregulation, and metabolite-dependent anti-inflammatory pathways, although much of the available human literature remains associative. Overall, current evidence supports dysbiosis as a disease modifier that may influence ocular inflammation, angiogenesis, neurodegeneration, and barrier stability. However, clinical translation remains limited by cohort heterogeneity, methodological variability, and incomplete control of confounding factors. Further progress will depend on longitudinal multi-omics cohorts and controlled intervention trials focused on actionable microbial functions.},
}

@article {pmid42194903,
year = {2026},
author = {Benites-Narcizo, G and Juvier-Riesgo, T and Pérez-Negrón, AP and García-Dussán, L and Wang, J and Hong, J and Mendoza-Santiesteban, CE and Lam, BL},
title = {Quantitative Flavoprotein Fluorescence Parameters in Retinal and Optic Nerve Diseases: A Scoping Review.},
journal = {Journal of clinical medicine},
volume = {15},
number = {10},
pages = {},
doi = {10.3390/jcm15103942},
pmid = {42194903},
issn = {2077-0383},
abstract = {Background: Retinal and optic nerve disorders remain major causes of visual morbidity worldwide. Ocular fundus flavoprotein fluorescence (FPF) imaging has emerged as a potential noninvasive biomarker of mitochondrial dysfunction for earlier detection and evaluation of disease severity. Methods: We conducted a Systematic Scoping Review of the diagnostic and correlational utility of quantitative FPF parameters in retinal and optic nerve diseases compared with healthy controls. Following PRISMA-ScR guidelines, we searched MEDLINE, Web of Science, Scopus, and CENTRAL for peer-reviewed human studies available online before 31 December 2025. Results: Seventeen studies were included, encompassing 1914 eyes and 1339 participants, and were predominantly cross-sectional. In healthy eyes, mean macular and optic nerve head FPF intensity were reported as 24.1 ± 12.2 gsu and 30.6 ± 14.6 gsu, respectively. Higher signals were reported in several disorders, including diabetes mellitus (76.0 [67.0-92.0] gsu), neovascular age-related macular degeneration (67.47 ± 17.77 gsu), and retinitis pigmentosa (50.5 ± 12.2 gsu). However, lower, unchanged, or stage-dependent signals were also observed within the same disease categories. Interpretation across studies was limited by substantial heterogeneity in patient selection, disease definitions, imaging protocols, control groups, and FPF outcome metrics. The precise cellular and sublayer origin of the detected signal also remains challenging to determine. Conclusions: Ocular fundus FPF imaging provides promising metabolic insight into retinal and optic nerve diseases. However, current evidence remains heterogeneous and largely cross-sectional, limiting clinical interpretability and generalizability. Longitudinal studies, technical standardization, and multimodal integration are needed to define reproducible disease-specific FPF profiles and improve translational applicability.},
}

@article {pmid42195076,
year = {2026},
author = {Çatak, O and Keleş, JK and Çatak, Z},
title = {Circulating Claudin-5 and Systemic Inflammatory Indices in Wet and Dry Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {5},
pages = {},
doi = {10.3390/medicina62050823},
pmid = {42195076},
issn = {1648-9144},
mesh = {Humans ; Female ; *Claudin-5/blood/analysis ; Male ; Case-Control Studies ; Prospective Studies ; Aged ; *Macular Degeneration/blood/physiopathology ; *Inflammation/blood ; Middle Aged ; Biomarkers/blood/analysis ; Aged, 80 and over ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease in which inflammation and blood-retinal barrier dysfunction may contribute to disease pathogenesis. Claudin-5 is a key tight-junction protein involved in endothelial barrier integrity. Hemogram-derived indices such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and pan-immune-inflammation value (PIV) reflect systemic inflammatory status. This study aimed to evaluate circulating claudin-5 levels and systemic inflammatory indices in patients with wet and dry AMD and to investigate their associations with visual function. Materials and Methods: This prospective case-control study included 90 participants: 30 patients with wet AMD, 30 patients with dry AMD, and 30 healthy controls. All participants underwent detailed ophthalmologic examination, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography. Serum claudin-5 levels were analyzed by enzyme-linked immunosorbent assay, and NLR, PLR, MLR, and PIV were calculated from complete blood count parameters. Group comparisons, correlation analyses, and age-adjusted analyses were performed using appropriate statistical methods. Results: Age differed significantly among the groups (p = 0.032), with the highest median age in the dry AMD group. BCVA (logMAR) also differed significantly (p < 0.001), and both AMD groups had worse visual acuity than controls. Median serum claudin-5 levels were 2.42 in controls, 3.28 in the wet AMD group, and 3.10 in the dry AMD group, with no significant between-group difference (p = 0.280). NLR, MLR, and PIV were also comparable among the groups (p = 0.310, p = 0.410, and p = 0.752, respectively). PLR differed among the groups (p = 0.019), and post hoc analysis showed higher PLR values in the dry AMD group than in the wet AMD group (p = 0.013). However, this difference was no longer statistically significant after adjustment for age (adjusted p = 0.098). Serum claudin-5 was not significantly correlated with age, BCVA, NLR, PLR, MLR, or PIV. Conclusions: Circulating claudin-5 did not differ significantly across AMD phenotypes and was not associated with age, visual function, or systemic inflammatory indices. Although PLR differed between wet and dry AMD before adjustment for age, the overall findings suggest that single-point peripheral serum measurements of claudin-5 may have limited utility in reflecting local retinal barrier-related changes in AMD. Larger longitudinal studies are needed to clarify its potential biomarker role.},
}

Humans
Female
*Claudin-5/blood/analysis
Male
Case-Control Studies
Prospective Studies
Aged
*Macular Degeneration/blood/physiopathology
*Inflammation/blood
Middle Aged
Biomarkers/blood/analysis
Aged, 80 and over

@article {pmid42195115,
year = {2026},
author = {Chang, HL and Wang, LU and Huang, TL and Chang, PY and Ho, WT and Hsu, YR and Chen, FT and Chen, YJ and Lin, CD and Wang, JK},
title = {The Short-Term Outcomes of Intravitreal Faricimab for Treatment-Naïve and -Refractory Neovascular Age-Related Macular Degeneration: A Real-World Study.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {5},
pages = {},
doi = {10.3390/medicina62050863},
pmid = {42195115},
issn = {1648-9144},
support = {NSTC 114-2221-E-003-037//National Science and Technology Council/ ; },
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections/methods ; Female ; Male ; Treatment Outcome ; Aged ; Visual Acuity/drug effects ; Aged, 80 and over ; *Macular Degeneration/drug therapy ; Polypoidal Choroidal Vasculopathy ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Middle Aged ; Angiogenesis Inhibitors/therapeutic use ; Antibodies, Bispecific ; },
abstract = {Background and Objectives: Neovascular age-related macular degeneration (nAMD), including typical nAMD (tAMD) and polypoidal choroidal vasculopathy (PCV), is a leading cause of visual impairment. This study investigated the real-world short-term outcomes of faricimab, a bispecific antibody targeting Ang-2 and VEGF-A, in patients with treatment-naïve or -refractory nAMD. Materials and Methods: This retrospective study analyzed treatment-naïve or -refractory nAMD eyes receiving one, two, or three monthly intravitreal faricimab injections. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) one month after the last injection. Secondary outcomes included the dry macula rate (absence of subretinal and intraretinal fluid) and subgroup comparisons between tAMD and PCV. Results: After a single injection, both treatment-naïve (n = 76) and -refractory (n = 44) eyes showed significant CFT reduction (p < 0.0001) but no significant BCVA improvement (p > 0.05). Dry macula was achieved in 63.2% of treatment-naïve and 71.4% of treatment-refractory eyes. In 38 treatment-naïve eyes receiving three injections, both CFT and BCVA significantly improved from baseline (p < 0.001 and p = 0.02, respectively), with a 94.7% dry macula rate. Subgroup analysis of those receiving three injections revealed that PCV eyes exhibited significant visual improvement, whereas tAMD eyes did not. No serious systemic or ocular adverse events were observed over the short-term follow-up period. Conclusions: Intravitreal faricimab is effective for both treatment-naïve and -refractory nAMD in the short term. While anatomical improvements were comparable between subtypes, the PCV subgroup showed a trend toward greater visual improvement in this small cohort; however, this may be influenced by the significantly younger age of PCV patients. These findings are exploratory and require validation in larger, age-matched prospective studies.},
}

Humans
Retrospective Studies
Intravitreal Injections/methods
Female
Male
Treatment Outcome
Aged
Visual Acuity/drug effects
Aged, 80 and over
*Macular Degeneration/drug therapy
Polypoidal Choroidal Vasculopathy
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Middle Aged
Angiogenesis Inhibitors/therapeutic use
Antibodies, Bispecific

@article {pmid42195150,
year = {2026},
author = {Jovanović, M and Milošević, J and Carrasco Guijarro, M and Jovanović, S and Todorović, D and Petrović, N and Paunović, S and Janićijević, K and Živković, MLJ},
title = {Outer Retinal Hyperreflective Foci as a Predictor of Hyperreflective Material Boundary Remodeling and Visual Outcomes in Neovascular Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {62},
number = {5},
pages = {},
doi = {10.3390/medicina62050895},
pmid = {42195150},
issn = {1648-9144},
mesh = {Humans ; Retrospective Studies ; Bevacizumab/therapeutic use ; Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; Female ; *Macular Degeneration/drug therapy/physiopathology ; Male ; Aged ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Intravitreal Injections ; Treatment Outcome ; *Retina/physiopathology ; },
abstract = {Purpose: The purpose of this study was to characterize the distribution and longitudinal evolution of intraretinal and subretinal hyperreflective foci (HF) in treatment-naive neovascular age-related macular degeneration (nAMD), and to examine associations between HF burden, hyperreflective material boundary remodeling (HRM-BR), and best-corrected visual acuity (BCVA) outcomes following bevacizumab treat-and-extend therapy. Methods: This was a retrospective observational study of 84 treatment-naive nAMD eyes receiving intravitreal bevacizumab via a treat-and-extend protocol. Spectral-domain OCT (Revo FC, Optopol) was performed at baseline (M0), month 3 (M3), and month 6 (M6). HF were quantified in the intraretinal and subretinal compartments using ImageJ software (version 1.54, National Institutes of Health, Bethesda, MD, USA) by two masked graders, with inter-rater agreement assessed by intraclass correlation coefficient (ICC). Eyes were classified into four HRM evolution patterns following the framework of Yu et al. Primary outcome was BCVA change from M0 to M6. Multivariable linear regression was performed to assess independent predictors of BCVA change. Results: Baseline intraretinal HF counts increased significantly across HRM Patterns 1 through 4 (median 0, 6, 4, and 8, respectively; Kruskal-Wallis p < 0.001; 95% CI for Spearman r = 0.471: [0.286, 0.623]). A higher baseline intraretinal HF count correlated with worse BCVA change at M6 (r = -0.300, 95% CI [-0.483, -0.092], p_adj = 0.010). In the primary multivariable model (n = 67), both intraretinal HF burden (β = -0.449, 95% CI [-0.879, -0.020], p = 0.041) and HRM width (β = -0.003, 95% CI [-0.005, -0.001], p = 0.014) were independent predictors of BCVA change. The transient M3 intraretinal HF peak in Pattern 3 eyes (median 4 → 12 → 4) was statistically confirmed by Wilcoxon signed-rank testing (M0 → M3: p = 0.004; M3 → M6: p = 0.001). Conclusions: Intraretinal HF burden is a graded marker of HRM pattern severity and an independent predictor of visual outcomes in nAMD, alongside HRM width. The statistically validated transient M3 HF peak in Pattern 3 may represent an early OCT signal of active boundary remodeling.},
}

Humans
Retrospective Studies
Bevacizumab/therapeutic use
Visual Acuity/physiology
Tomography, Optical Coherence/methods
Female
*Macular Degeneration/drug therapy/physiopathology
Male
Aged
Angiogenesis Inhibitors/therapeutic use
Aged, 80 and over
Intravitreal Injections
Treatment Outcome
*Retina/physiopathology

@article {pmid42195311,
year = {2026},
author = {Hajdari, A and Uka, V},
title = {Real-World Experience with Brolucizumab in Treatment-Naïve nAMD with Low Baseline Visual Acuity: Short-Term Outcomes from a Prospective Single-Institution Study.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/life16050754},
pmid = {42195311},
issn = {2075-1729},
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a progressive chronic disease that represents a major cause of irreversible vision loss worldwide. In this study we aim to assess the short-term functional and anatomical outcomes of brolucizumab therapy in treatment-naïve patients with nAMD presenting with low baseline visual acuity in a single institution setting.

METHODS: This is a prospective non-randomized study that included 154 treatment-naïve eyes with low baseline visual acuity. We measured visual outcomes (BCVA, logMAR) and structural outcomes (CST, μm). We also stratified the study population into respective age subgroups to evaluate any possible trend between outcome changes and age differences. BCVA and CST were measured at baseline, at each consecutive month (month 1, 2 and 3) of the loading phase, as well as at the final timepoint (6 months). Intraocular pressure (IOP) before and after injection, as well as the incidence of serious adverse events, were monitored throughout the study.

RESULTS: Mean BCVA improved by 0.41 logMAR (+20 ETDRS letters) after the first injection, 0.65 logMAR (+32 letters) after the second, and reached a maximum improvement of 0.80 logMAR after the third injection. The most important BCVA improvement was seen in younger patients (<50 years), with mean BCVA decreasing from approximately 1.0 logMAR at baseline to around 0.3-0.4 logMAR at the final measurement. Mean CST declined by 45.5 μm after the first injection, 78.5 μm after the second, 117.8 μm after the third, and 143.6 μm at the final timepoint, indicating a pronounced anatomical response to intravitreal brolucizumab therapy.

CONCLUSIONS: In conclusion, this study demonstrates that brolucizumab therapy provides significant short-term anatomical and functional improvements in treatment-naïve patients with nAMD and poor baseline visual acuity. Baseline visual acuity, treatment-naïve status, and patient age appear to be key determinants of visual gain.},
}

@article {pmid42195365,
year = {2026},
author = {Skarbek, D and Sochocka, A and Sidło, O and Sapiaszko, A and Drab, A and Baj, J and Rejdak, R and Dolar-Szczasny, J},
title = {Nanocarrier-Based Ocular Drug Delivery Systems for Retinal Diseases: Therapeutic Potential.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {5},
pages = {},
doi = {10.3390/life16050810},
pmid = {42195365},
issn = {2075-1729},
abstract = {BACKGROUND: Posterior segment eye diseases, including age-related macular degeneration and diabetic retinopathy, are preeminent causes of vision loss worldwide. Effective drug delivery to the retina poses an ongoing therapeutic difficulty due to the presence of the anatomical and physiological barriers. Nanotechnology-based drug delivery systems represent a promising strategy to overcome those limitations.

METHODS: A narrative literature review was conducted using the PubMed, Scopus, and Google Scholar databases, covering publications published between 2019 and 2026. Publications evaluating nanoparticles for the treatment of the vitreoretinal disorders, including pre-clinical in vitro and in vivo studies, were analyzed.

RESULTS: Nanocarriers, including liposomes, polymeric nanoparticles, and lipid-based systems, established improved drug bioavailability, stability, and targeted delivery. The analyzed systems facilitate sustained drug release and potentially reduce the prevalence of invasive intravitreal injections. The nanocarriers' effectiveness is primarily influenced by their physicochemical properties, such as particle size, surface charge, and encapsulation efficiency. Nonetheless, the production costs and safety aspects, including cytotoxicity, oxidative stress, and inflammatory responses, remain as significant limitations.

CONCLUSIONS: Nanotechnology-based drug delivery systems serve as an auspicious therapeutic approach for posterior segment eye diseases. However, further standardized preclinical and clinical research is required to assure long-term safety and enable successful clinical transition.},
}

@article {pmid42196569,
year = {2026},
author = {De Silva, S and Xu, B},
title = {Beneficial Effects of Natural Bioactive Compounds on Eye Health: A Narrative Review.},
journal = {International journal of molecular sciences},
volume = {27},
number = {10},
pages = {},
doi = {10.3390/ijms27104592},
pmid = {42196569},
issn = {1422-0067},
support = {UICR0400015-24B & UICR0400016-24B//Beijing Normal-Hong Kong Baptist University/ ; },
mesh = {Humans ; Animals ; *Eye Diseases/drug therapy/metabolism ; Antioxidants/pharmacology/therapeutic use ; *Biological Products/pharmacology/therapeutic use ; Oxidative Stress/drug effects ; Flavonoids/pharmacology/therapeutic use ; *Eye/drug effects/metabolism ; Polyphenols/pharmacology/therapeutic use ; Macular Degeneration/drug therapy ; Fatty Acids, Omega-3/pharmacology/therapeutic use ; Carotenoids/pharmacology/therapeutic use ; },
abstract = {Ocular diseases like age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and cataracts are major causes of visual impairment all over the world and are closely linked to oxidative stress, inflammation and mitochondrial dysfunction. This narrative review critically summarizes the available evidence on how various natural bioactive compounds, such as carotenoids, polyphenols, flavonoids, omega-3 fatty acids and botanical extracts, can affect important molecular pathways associated with ocular degeneration. Their antioxidant, anti-inflammatory, anti-angiogenic and neuroprotective properties are given particular emphasis, especially regarding the Nrf2, NF-κB and VEGF signaling pathways. This review is different from past reviews that simply discuss the potential of bioactives in the general nutritional context; rather, it unfolds the disease-specific mechanisms and compound-specific molecular actions and gives special attention to recent advances in nano-delivery systems and precision nutrition strategies to increase the bioavailability and therapeutic targeting of these nutrients in the eyes. Moreover, it offers a framework for a comparison of evidence between preclinical and clinical studies, as well as identifying current translational gaps, including limited bioavailability and a lack of long-term clinical trials, and suggesting future directions such as genotype-guided nutrition and microbiome-informed interventions. In general, this review provides a mechanistic and translational overview of how dietary bioactive compounds relate to eye health and offers the perspective of their possible use in prevention and complementary treatment for vision-related diseases.},
}

Humans
Animals
*Eye Diseases/drug therapy/metabolism
Antioxidants/pharmacology/therapeutic use
*Biological Products/pharmacology/therapeutic use
Oxidative Stress/drug effects
Flavonoids/pharmacology/therapeutic use
*Eye/drug effects/metabolism
Polyphenols/pharmacology/therapeutic use
Macular Degeneration/drug therapy
Fatty Acids, Omega-3/pharmacology/therapeutic use
Carotenoids/pharmacology/therapeutic use

@article {pmid42196841,
year = {2026},
author = {Vilkeviciute-Petraite, A and Bruzaite, A and Cebatoriene, D and Zaliuniene, D and Lukosevicius, R and Skieceviciene, J and Kupcinskas, J and Liutkeviciene, R},
title = {The Role of Kynurenine and 5-Hydroxytryptophan in Modulating Microbiota and Their Implications in Exudative Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {10},
pages = {},
doi = {10.3390/diagnostics16101475},
pmid = {42196841},
issn = {2075-4418},
support = {No. S-MIP-23-96//Lietuvos Mokslo Taryba/ ; },
abstract = {Background/Objectives: This study explores the roles of kynurenine and 5-hydroxytryptophan (5-HTP) in modulating gut microbiota and their potential implications for exudative age-related macular degeneration (AMD). By examining the interplay between these metabolites and the microbiome, we aim to uncover novel pathways that may influence the pathogenesis of AMD. Understanding these associations could lead to innovative therapeutic approaches for managing this leading cause of vision loss in the elderly. To investigate the roles of kynurenine and 5-HTP, alongside the composition of the nasopharyngeal microbiota, in patients with exudative AMD. Methods: Blood metabolite profiling was performed using LC-MS-based metabolomics. Metabolites were extracted with cold methanol/water containing internal standards, filtered through a 10 kDa cutoff filter, separated on a ZIC-HILIC HPLC column, and detected using an Orbitrap mass spectrometer. Metabolites were identified using MZmine 2 software. Results: Patients with exudative AMD exhibited a profound systemic shift in tryptophan metabolism, characterized by significantly lower plasma levels of 5-HTP and higher levels of kynurenine compared to control subjects (p < 0.001 for both). Logistic regression analysis confirmed that both metabolites were independent predictors of AMD status; higher kynurenine levels were associated with increased disease probability, while higher 5-HTP levels demonstrated a protective effect. The kynurenine/5-HTP ratio emerged as a robust biomarker, achieving an area under the curve (AUC) of 0.85 with an optimal threshold of 3.43 (74.1% sensitivity, 84.4% specificity). When integrated with age and gender, the diagnostic performance of the model reached an excellent AUC of 0.92. After adjusting for demographic factors, the kynurenine/5-HTP ratio remained a potent independent risk factor, with each unit increase associated with a 6.30-fold increase in the odds of exudative AMD. Conclusions: Exudative AMD is characterized by a shift in tryptophan metabolism toward the kynurenine pathway, with decreased 5-HTP, increased kynurenine, and an elevated kynurenine/5-HTP ratio. This ratio showed a strong independent association with AMD and excellent diagnostic performance, highlighting its potential as a biomarker and its role in disease pathogenesis.},
}

@article {pmid42196921,
year = {2026},
author = {Prus-Ludwig, A and Wylęgała, A and Wylęgała, E and Kijonka, M and Wowra, B},
title = {Optical Coherence Tomography Biomarkers Predicting Progression to Atrophy in Non-Exudative Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {10},
pages = {},
doi = {10.3390/diagnostics16101555},
pmid = {42196921},
issn = {2075-4418},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. Geographic atrophy (GA) is an advanced, currently incurable stage of non-exudative AMD and is characterized by progressive atrophy of the retinal pigment epithelium and outer retina, resulting in substantial visual impairment. Optical coherence tomography (OCT) has revolutionized the diagnosis and monitoring of AMD by enabling in vivo visualization of retinal microstructure and identification of imaging biomarkers associated with progression to late-stage disease. Improved understanding of these lesions may clarify disease pathogenesis and inform the development of new therapeutic strategies and clinical trial endpoints. This review summarizes OCT-based biomarkers reported as predictors of progression to late atrophic forms of AMD, with emphasis on early atrophic changes that precede GA.},
}

@article {pmid42197042,
year = {2026},
author = {Azalati, MM and Jiang, H and Zhang, K and Kong, L and Wang, L and Li, Z and Fan, Y and Chen, F and Ma, L and Zhang, W},
title = {Dietary Patterns and Age-Related Macular Degeneration: A Matched Case-Control Study.},
journal = {Nutrients},
volume = {18},
number = {10},
pages = {},
doi = {10.3390/nu18101582},
pmid = {42197042},
issn = {2072-6643},
support = {82373570//The National Natural Science Foundation of China/ ; xtr052023010//The Fundamental Research Funds of Xi'an Jiaotong University/ ; },
mesh = {Humans ; *Macular Degeneration/prevention & control/epidemiology/etiology ; Case-Control Studies ; Female ; Male ; Aged ; *Feeding Behavior ; *Diet ; Odds Ratio ; Logistic Models ; Risk Factors ; Fruit ; Vegetables ; Middle Aged ; Principal Component Analysis ; Multivariate Analysis ; Aged, 80 and over ; Diet, Healthy ; },
abstract = {Background: Previous research on diet and age-related macular degeneration (AMD) has emphasized primarily particular nutrients or foods, and the influence of comprehensive dietary patterns that represent actual eating behaviors is largely unknown. Objective: The aim of this study was to assess the association between dietary patterns and the odds of AMD. Methods: A case-control study involving 246 participants with AMD and 246 controls are individually matched by age and gender. Dietary patterns were identified through principal component analysis using a validated food frequency questionnaire. Multivariable conditional logistic regression models were applied to examine the association between the extracted dietary patterns and the likelihood of AMD. Results: Three major dietary patterns were found, accounting for 50.59% of the total variance explained. The prudent dietary pattern represented a high intake of vegetables, fruits, soybeans and its products, edible fungi and algae, and nuts were associated with reduced odds ratios (ORs) of the highest tertile compared to the lowest tertile (OR, 0.29, 95% confidence interval [CI], 0.14-0.59, p for trend = 0.001). The estimated likelihood for AMD in the highest tertile of egg and milk dietary pattern intake, which is characterized by a high intake of eggs, milk and dairy products, and refined grains, was 0.40 (95% CI, 0.23-0.67, p for trend < 0.001) compared with those in the lowest tertile. No association with AMD was identified for the animal dietary pattern (p > 0.05). Conclusions: Adherence to dietary patterns rich in fruits, vegetables, nuts, refined grains, eggs, milk and dairy products is associated with reduced odds of AMD, emphasizing the potential relevance of dietary habits to visual health among middle-aged and elderly adults.},
}

Humans
*Macular Degeneration/prevention & control/epidemiology/etiology
Case-Control Studies
Female
Male
Aged
*Feeding Behavior
*Diet
Odds Ratio
Logistic Models
Risk Factors
Fruit
Vegetables
Middle Aged
Principal Component Analysis
Multivariate Analysis
Aged, 80 and over
Diet, Healthy

@article {pmid42198422,
year = {2026},
author = {Chakraborty, D and Sinha, TK and Sinha, S and Biswas, RK and Das, A and Maiti, A and Bhattacharya, R and Dan, S and Rungta, D and Das, S},
title = {Real-World Comparison of Biosimilar Ranibizumab (Ranieyes) and Innovator Ranibizumab (Lucentis/Accentrix) Across Multiple Retinal Vascular Diseases (The BRIO Study).},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {5},
pages = {},
doi = {10.3390/ph19050747},
pmid = {42198422},
issn = {1424-8247},
abstract = {Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence.},
}

@article {pmid42198424,
year = {2026},
author = {Tsai, HR and Hsu, JZ and Loh, CH and Huang, HK},
title = {PCSK9 Inhibitor Use and the Risk of Age-Related Macular Degeneration in Patients with Atherosclerotic Cardiovascular Disease.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {5},
pages = {},
doi = {10.3390/ph19050750},
pmid = {42198424},
issn = {1424-8247},
support = {TCRD115-012//Hualien Tzu Chi Medical Center/ ; },
abstract = {Background/Objectives: Emerging evidence suggests that alterations in lipid metabolism may play a contributing role in the pathogenesis of age-related macular degeneration (AMD). Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, a novel class of lipid-lowering agents, offer anti-inflammatory and antioxidant benefits, which may provide protective effects against AMD. We aimed to evaluate the risk of developing AMD among patients with atherosclerotic cardiovascular disease (ASCVD) who were newly treated with PCSK9 inhibitors compared with those receiving statins. Methods: This retrospective cohort study utilized data from the Global Collaborative Network within the TriNetX Research Network. Patients with ASCVD who were newly initiated on PCSK9 inhibitors or statins were identified and matched for age, sex, race, laboratory data, comorbidities, and concomitant medications. The primary outcomes were the hazard ratios (HRs) for developing AMD, dry AMD, and wet AMD. Propensity score matching (PSM) was used to adjust for baseline demographics and comorbidities. Results: After PSM, 50,102 patients were included in each group (PCSK9 inhibitor users vs. statin users). Compared to statin users, PCSK9 inhibitor users had significantly lower risks of AMD (HR, 0.81; 95% confidence interval [CI], 0.72-0.92) and dry AMD (HR, 0.78; 95% CI, 0.65-0.94), but not wet AMD (HR, 0.90; 95% CI, 0.70-1.16). Stratified and subgroup analyses showed reduced AMD risk among patients aged ≥65 years, White patients, female patients, and evolocumab users. Conclusions: In patients with ASCVD, compared with use of statins, use of PCSK9 inhibitors is associated with reduced risks of AMD and dry AMD, suggesting a potential novel strategy for managing a condition with limited therapeutic options.},
}

@article {pmid42199036,
year = {2026},
author = {Karunainathan, MG and Lee, C and Zohalinejad, KD and Mæng, MO and Fabrin, NW and Jónsdóttir, S and Hassing, AK and Yde, SK and Wykoff, CC and Vorum, H and Subhi, Y and Ørskov, M and Cehofski, LJ},
title = {Real-world insights on switching aflibercept dosage for enhanced outcomes in age-related macular degeneration (RISE-AMD): Safety data.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70160},
pmid = {42199036},
issn = {1755-3768},
abstract = {PURPOSE: To evaluate real-world safety experience with aflibercept 8 mg in a large case series of patients with neovascular age-related macular degeneration (nAMD).

METHODS: Due to a high proportion of patients on short treatment intervals, patients with nAMD at a Danish tertiary retina clinic were systematically switched to aflibercept 8 mg. Safety data from May 2024 to October 2025 were obtained through a retrospective review of medical records by an experienced retina specialist and an additional reviewer. Symptomatic intraocular pressure (IOP) increase was defined as any symptom (e.g. pain) in conjunction with IOP > 21 mmHg.

RESULTS: In total, 8675 intravitreal injections of aflibercept 8 mg were administered in 1429 eyes with nAMD, including 139 glaucomatous eyes. A total of 25 AEs were reported (2.88 per 1000 injections). Intraocular inflammation (IOI) was reported in 11 eyes (1.27 per 1000 injections), with 10 eyes being managed with topical dexamethasone, while one case required vitrectomy. Symptomatic IOP increase was observed in 10 cases (1.15 per 1000 injections). The occurrence of symptomatic IOP increase did not differ between glaucomatous and non-glaucomatous eyes (p = 0.24). Two cases of bacterial endophthalmitis were registered. No case of retinal vasculitis or retinal vascular occlusion was observed.

CONCLUSION: Incidence rates of symptomatic IOP increase and IOI were generally low. Despite a large glaucoma cohort, the higher incidence rate of symptomatic IOP increase in glaucomatous eyes did not reach statistical significance.},
}

@article {pmid42199109,
year = {2026},
author = {Ni, Y and Li, J and So, KF},
title = {Beyond antioxidation: Retinal neuroprotection by Lycium barbarum polysaccharides via multiple signaling pathways.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01602},
pmid = {42199109},
issn = {1673-5374},
abstract = {Age-related macular degeneration, glaucoma, retinitis pigmentosa, and diabetic retinopathy are the major retinal degenerative disorders, and each ultimately leads to irreversible vision loss. In this context, single-target therapies aimed at isolated pathways have delivered only modest benefits. Lycium barbarum polysaccharides, the predominant bioactive components of goji berries, emerge as far more than simple antioxidants, functioning instead as orchestrators of interconnected signaling networks. Growing evidence shows that Lycium barbarum polysaccharides engages pathways well beyond redox control to interrupt disease-driving cascades: it limits cellular senescence through the SIRT1/p53 axis, preserves blood-retinal barrier integrity by maintaining aquaporin-4 at astrocytic endfeet, and biases microglia from proinflammatory M1 toward reparative M2 states. Beyond immunomodulation, Lycium barbarum polysaccharides promotes clearance of pathogenic protein aggregates and suppresses pathological neovascularization via the miR-15a-5p/ VEGFR2 axis. While antioxidant effects may predominate in early disease, the actions of LBP become more targeted as pathology advances, a stage-dependent selectivity that helps explain its cross-disease efficacy. In age-related macular degeneration, Lycium barbarum polysaccharides sustains metabolic homeostasis in retinal pigment epithelium by tuning autophagic flux through the miR-181/BCL-2 axis. In glaucoma, it safeguards mitochondrial membrane potential in retinal ganglion cells, supporting energy metabolism and survival. Collectively, these properties position Lycium barbarum polysaccharides as a pleiotropic regulator capable of reshaping multiple disease trajectories. Realizing its clinical potential will require precise identification of active metabolites, rigorous in vivo pharmacokinetic profiling, and rational combination with current standard-of-care therapies.},
}

@article {pmid42199324,
year = {2026},
author = {Cukurova, F and Ramsey, DJ},
title = {Rapid Macular Thinning as a Biomarker for Geographical Atrophy.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {602755},
pmid = {42199324},
issn = {1177-5467},
abstract = {PURPOSE: To assess the rate of retinal thinning as a biomarker for incident late-stage age-related macular degeneration (AMD).

METHODS: This retrospective cohort study included patients (aged ≥50 years) with ≥3 optical coherence tomography (OCT) macular scans ≥6 months apart. Eyes that developed ≥250 μm of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) with associated hypertransmission through Bruch's membrane on OCT were considered to have developed geographic atrophy (GA). The spatial pattern of macular thinning was assessed using the ETDRS rings centered on the foveola, calculated as a percentage change relative to its baseline value by eye.

RESULTS: A total of 201 eyes met inclusion criteria. At last follow-up, 17 eyes developed GA (8.5%) at a median observation of 5.2 (2.4) years. The central subfield (1-mm) and inner ring (3-mm ETDRS subfield) thinned faster in eyes that developed incipient GA (central subfield thickness [CST]: -1.59% vs. -0.47% per year, p=0.007; inner ring: -1.48% vs. -0.65% per year, p<0.001), while the outer ring (6-mm ETDRS subfield) thinned less rapidly (-0.75% vs. -0.30% per year, p=0.003). Linear regression identified the rate of inner ring thinning as the most significant predictor of GA, with a receiver operating characteristic curve demonstrating a high predictive accuracy (area under the curve [AUC], 0.821; 95% CI, 0.746-0.896; p<0.001).

CONCLUSION: Rapid thinning of the inner ETDRS ring is associated with incipient GA. Identifying eyes at risk of late AMD using serial OCT scans would permit personalized monitoring and treatment strategies critical for safeguarding vision.},
}

@article {pmid42200766,
year = {2026},
author = {Invernizzi, A and Romano, F and Corvi, F and Cozzi, M and Sadda, SR and Freund, KB and Staurenghi, G},
title = {Real-Time High-Resolution OCT for Imaging Retinal and Choroidal Blood Flow.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {69},
doi = {10.1167/iovs.67.5.69},
pmid = {42200766},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; *Regional Blood Flow/physiology ; Cross-Sectional Studies ; *Retinal Vessels/physiology/diagnostic imaging ; Female ; Male ; Blood Flow Velocity/physiology ; Middle Aged ; Feasibility Studies ; Aged ; *Retinal Diseases/physiopathology ; },
abstract = {PURPOSE: To evaluate the feasibility of visualizing intravascular moving particles within retinal and choroidal vessels using real-time high-resolution optical coherence tomography (High-Res OCT), a prototype device offering 3-µm axial resolution.

METHODS: In this cross-sectional study, 20 healthy eyes were imaged using both High-Res OCT and the standard SPECTRALIS HRA+OCT. A dedicated in-built research tool enabled ART-1 B-scan movie acquisition with real-time eye-tracking. Two masked graders qualitatively assessed visibility and direction of intravascular moving particles, and intergrader agreement was evaluated using Gwet's agreement coefficient 1 (AC1). Four additional patients with retinal vascular disorders (retinal artery occlusion, diabetic retinopathy, hypertensive retinopathy, and neovascular age-related macular degeneration) were imaged with High-Res OCT to explore illustrative clinical applications.

RESULTS: High-Res OCT demonstrated superior visualization of intravascular moving particles compared with standard OCT in both arteries (80% vs. 50%; P = 0.01) and veins (90% vs. 60%; P = 0.03). Intergrader agreement was high for High-Res OCT (AC1, 0.82-0.89) and moderate-to-substantial for standard OCT (AC1, 0.53-0.71). Flow direction assessment did not differ significantly between devices, although correct identification was numerically higher with High-Res OCT. In pathological eyes, real-time High-Res OCT enabled dynamic visualization of pulsatile and disturbed flow patterns and distinct intravascular motion across multiple vascular conditions.

CONCLUSIONS: Real-time High-Res OCT enables direct, non-invasive visualization of intravascular moving particles within retinal and choroidal vessels and improves flow detectability compared with conventional OCT. This technique offers novel qualitative insights into ocular vascular dynamics and may guide future quantitative and translational applications.},
}

Humans
*Tomography, Optical Coherence/methods
*Choroid/blood supply/diagnostic imaging
*Regional Blood Flow/physiology
Cross-Sectional Studies
*Retinal Vessels/physiology/diagnostic imaging
Female
Male
Blood Flow Velocity/physiology
Middle Aged
Feasibility Studies
Aged
*Retinal Diseases/physiopathology

@article {pmid42201156,
year = {2026},
author = {Fathee, HN and Babayev, R and Sahmoud, S and Ağaoğlu, N},
title = {Advancing AMD Detection: Dataset Design and Deep Learning Optimization for Unconstrained Retinal Images.},
journal = {Vision (Basel, Switzerland)},
volume = {10},
number = {2},
pages = {},
doi = {10.3390/vision10020028},
pmid = {42201156},
issn = {2411-5150},
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of vision impairment worldwide, making early and accurate detection essential for effective clinical intervention. Recent advances in deep learning have demonstrated promising results in automated retinal image analysis; however, most existing approaches rely on datasets acquired under controlled conditions, limiting their generalizability to real-world clinical environments. In this paper, we propose a novel AMD dataset designed to simulate unconstrained imaging conditions, by incorporating noise, luminance variations, and device-related artifacts commonly encountered during retinal scan acquisition. Using this dataset, we conduct a comprehensive comparative evaluation of six widely adopted deep learning architectures: VGG16, VGG19, InceptionV3, MobileNetV2, ResNet50, and DenseNet. Experimental results indicate notable performance variations across models, highlighting the impact of architectural design on robustness to image degradation. Among the evaluated approaches, VGG16 achieved the best overall performance. By further optimizing this architecture through targeted training and fine-tuning strategies, the proposed system reached an accuracy of 88% in AMD detection. These findings demonstrate the effectiveness of the optimized VGG16 model and underline the importance of realistic datasets for developing reliable deep learning-based diagnostic tools for practical clinical settings.},
}

@article {pmid42201157,
year = {2026},
author = {Lixi, F and Troisi, M and Calabresi, V and Giagoni, A and Rossi, C and Timofte-Zorila, MM and Tarași, TC and Vitiello, L and Tomi, MI and Gheorghe, AG and Coco, G and Lanzolla, G and Giannaccare, G},
title = {Beyond Glycemic Control: Ocular Effects of Glucagon-like Peptide-1 Receptor Agonists.},
journal = {Vision (Basel, Switzerland)},
volume = {10},
number = {2},
pages = {},
doi = {10.3390/vision10020029},
pmid = {42201157},
issn = {2411-5150},
abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and newer dual-incretin therapies have become central to the treatment of diabetes mellitus and obesity, with benefits extending beyond glycemic control. Their expanding use has prompted growing interest in their potential ocular effects. Experimental data support plausible protective mechanisms, including reduction in oxidative stress and neuroprotective effects on retinal and optic nerve tissues. Clinical evidence, however, remains heterogeneous. In diabetic retinopathy, the main concern appears to be transient early worsening associated with rapid glycemic improvement rather than direct retinal toxicity. A potential semaglutide-associated signal for non-arteritic anterior ischemic optic neuropathy has raised concern, although the absolute risk appears low and causality remains unproven. Emerging studies also suggest possible beneficial associations with glaucoma, ocular surface diseases, and certain retinal vascular outcomes, whereas the evidence regarding age-related macular degeneration and cataract remains conflicting or preliminary. Overall, ocular outcomes associated with incretin-based therapies seem to reflect a complex interplay among drug-specific pharmacology, systemic metabolic changes, and individual patient susceptibility rather than a class effect. Baseline ophthalmic assessment and individualized follow-up may be advisable in selected high-risk patients. Further prospective ophthalmology-focused studies are needed to clarify long-term safety and identify the patients most likely to benefit or develop adverse events.},
}

@article {pmid42201532,
year = {2026},
author = {Mimura, T and Nishijima, Y and Hasegawa, D and Yoshida, Y and Noma, H},
title = {Global association between ambient air pollution and age-related macular degeneration: an ecological analysis across 203 countries.},
journal = {Environmental science and pollution research international},
volume = {},
number = {},
pages = {},
pmid = {42201532},
issn = {1614-7499},
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment worldwide, and both environmental and lifestyle factors have been implicated in its development; however, international-scale evidence regarding the impact of air pollution remains limited. We conducted a cross-sectional ecological study to evaluate national-level associations between AMD burden and environmental as well as lifestyle factors using data from the Global Burden of Disease study. Disability-adjusted life years (DALYs), age-standardized DALYs, and age-standardized prevalence of AMD from 1990 to 2020 were analyzed in relation to ambient air pollutants, including particulate matter ≤ 2.5 μm (PM2.5), PM ≤ 10 μm (PM10), nitrogen dioxide, sulfur dioxide, ozone, household air pollution from solid fuel use, and national smoking prevalence obtained from global databases. Between 1990 and 2020, global DALYs attributable to AMD increased by 26.7%, whereas age-standardized DALYs and age-standardized prevalence decreased by 19.2% and 3.4%, respectively. In 2020, age-standardized AMD prevalence showed significant positive correlations with PM2.5 (r = 0.65, p < 0.001), ozone (r = 0.55, p < 0.001), and household air pollution (r = 0.30, p < 0.001), and a significant negative correlation with smoking prevalence (r = -0.25, p < 0.001). Multivariable regression analyses identified PM2.5 (odds ratio [OR] 8.09, p < 0.001) and ozone (OR 5.42, p < 0.001) as independent predictors of AMD prevalence. These findings suggest that exposure to ambient air pollution, particularly fine particulate matter and ozone, may contribute to the global burden of AMD and represent potentially modifiable risk factors, underscoring the need for further research to clarify causal relationships and to inform public health and environmental policy interventions.},
}

@article {pmid42182542,
year = {2026},
author = {Al-Tamimi, NY and Amer, M and Graini, FNE},
title = {Clinical Low Vision Rehabilitation Interventions in Age-Related Macular Degeneration: A Case Report.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e109419},
pmid = {42182542},
issn = {2168-8184},
abstract = {A 70-year-old female with bilateral age-related macular degeneration (AMD) - wet AMD in the right eye and dry AMD in the left eye - presented with reduced unaided distance visual acuity of 20/200 (6/60) and near visual acuity of 3.2M (20/160, 6/48) OU. Retinoscopy and subjective refraction showed a prescription of -2.25 -2.50 × 175 in the right eye and +0.50 -1.50 × 120 in the left eye, achieving corrected visual acuities of 20/125 (6/37.5) OU. With an additional +3.00 diopters sphere for near tasks, the patient was able to read up to 2.5M (20/125, 6/37.5), indicating a coexisting refractive error. Amsler grid testing revealed central metamorphopsia and scotomas OU. Optical coherence tomography (OCT) confirmed bilateral drusen, retinal pigment epithelium (RPE) atrophy, and vitreomacular adhesion (VMA), with findings consistent with AMD. Functional contrast sensitivity was reduced (20/100, 6/30) OU, and visual field testing showed central scotomas and metamorphopsia. Low vision rehabilitation included the prescription of a 2.5× binocular Galilean telescope (Eschenbach 1639; Eschenbach Optik GmbH, Nuremberg, Germany) for distance, achieving 20/40 (6/12) vision OU, and a 5× illuminated hand magnifier (Eschenbach Mobilux 15105; Eschenbach Optik GmbH) for near tasks, enabling reading of 1.0M print (approximately 20/50, equivalent to 6/18+). Environmental modifications and contrast-enhancing filters were recommended. Nutritional counseling and ongoing monitoring were initiated, and the patient was educated on self-assessment with the Amsler grid. At three-month follow-up, visual function remained stable, and low vision strategies continued to support functional independence. This case underscores the importance of early low vision intervention, multidisciplinary care, and personalized rehabilitation strategies in maintaining quality of life in patients with AMD.},
}

@article {pmid42184268,
year = {2026},
author = {Xu, X and Liu, W and Li, H and Wang, Y and Li, Y and Wang, B and Liu, M and Li, Y},
title = {The Trajectory of Retinal Microcirculation Imaging: From Angiography to Artificial Intelligence.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {231},
pages = {},
doi = {10.3791/70115},
pmid = {42184268},
issn = {1940-087X},
mesh = {Humans ; *Artificial Intelligence ; *Retinal Vessels/diagnostic imaging/physiology ; Microcirculation/physiology ; Tomography, Optical Coherence/methods ; Animals ; *Angiography/methods ; },
abstract = {Retinal and choroidal microcirculation are highly specialized vascular networks essential for vision and are increasingly recognized as indicators of systemic diseases. For decades, its assessment relied on invasive dye-based angiography, which infers pathology from secondary effects such as vascular leakage. A paradigm shift is now underway, driven by non-invasive imaging modalities that directly visualize and quantify the microvasculature with unprecedented resolution. Chief among these is optical coherence tomography angiography, which provides depth-resolved, three-dimensional maps of perfused vessels, enabling the generation of objective biomarkers for vascular integrity and ischemia. Complementary techniques further probe absolute blood flow, high-frequency hemodynamics, and cellular-level perfusion, creating a rich, multi-scale dataset. This technological evolution is transforming clinical practice, facilitating preclinical detection of diabetic retinopathy, refining therapeutic strategies for neovascular age-related macular degeneration, and providing new insights into the vascular contributions to glaucoma. Looking ahead, integrating these multimodal data streams with artificial intelligence promises to convert the wealth of information into predictive models of disease risk and progression. This heralds a new era in precision ophthalmology and oculomics (the large-scale, data-driven analysis of ocular imaging biomarkers to assess systemic health and predict disease risk), with transformative gains in processing, quantification, and access.},
}

Humans
*Artificial Intelligence
*Retinal Vessels/diagnostic imaging/physiology
Microcirculation/physiology
Tomography, Optical Coherence/methods
Animals
*Angiography/methods

@article {pmid42184794,
year = {2026},
author = {Stitou, B and Hung, J and Tran, THC},
title = {[Comparison between in-person physical examination and telemedicine with portable equipment in elderly fall-risk patients].},
journal = {Journal francais d'ophtalmologie},
volume = {49},
number = {6},
pages = {104901},
doi = {10.1016/j.jfo.2026.104901},
pmid = {42184794},
issn = {1773-0597},
abstract = {PURPOSE: To assess diagnostic and clinical decision concordance between a face-to-face ophthalmological examination using handheld equipment and an asynchronous teleophthalmology assessment in disabled elderly fall-risk patients as well as the feasibility of this approach.

PATIENTS AND METHODS: This prospective single-center study evaluated a diagnostic method. Disabled elderly fall-risk patients underwent an in-person ophthalmological examination using a handheld slit-lamp followed by an asynchronous teleophthalmology assessment based on videos acquired by handheld anterior segment and fundus cameras. Diagnostic and management concordance were assessed using Cohen's kappa coefficient. Feasibility was evaluated by the rate of readable examinations.

RESULTS: A total of 142 patients (281 eyes) were included. Concordance was very good for phakic/pseudophakic status assessment (kappa=0.87-0.96), moderate for lens assessment (kappa=0.51-0.58) and macular evaluation (kappa=0.48-0.57), and low for other anterior (cornea, iris) and posterior segment (optic nerve head, retinal vessels) assessment as well as for overall clinical decision-making (kappa=0.15-0.35). Feasibility was excellent for anterior segment examination (90-98%) and acceptable for posterior segment assessment (61-81%). A clinical decision could be proposed via teleophthalmology in 50-72% of cases. The main causes of visual impairment were cataract, age-related macular degeneration, and optic neuropathy.

CONCLUSION: Asynchronous teleophthalmology using handheld equipment appears feasible in disabled elderly patients, with variable reliability depending on the parameters assessed. Technological, organizational, and methodological improvements are required before broader implementation.},
}

@article {pmid42186202,
year = {2026},
author = {Chang, TW and Kuo, CY and Lee, CY and Hung, CH},
title = {GLP-1 Receptor Agonists and Risk of Age-Related Macular Degeneration in Older Adults With Obesity: A Target Trial Emulation.},
journal = {Diabetes, obesity & metabolism},
volume = {},
number = {},
pages = {},
doi = {10.1111/dom.70910},
pmid = {42186202},
issn = {1463-1326},
abstract = {AIMS: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. Whilst glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly prescribed for obesity management, their potential impact on AMD risk in individuals without diabetes remains unclear. This study aimed to evaluate the association between GLP-1RA initiation and the risk of incident AMD in obese adults without diabetes.

MATERIALS AND METHODS: We conducted a target trial emulation using the TriNetX global health research network (January 2014-June 2025). Eligible participants were adults aged ≥ 60 years with obesity but without diabetes mellitus. New users of GLP-1RAs were compared with new users of other weight-loss medications. Following 1:1 propensity score matching, Cox proportional hazards models estimated hazard ratios (HRs) for incident AMD over a maximum 7-year observation window (median follow-up: 1.11 years [IQR: 1.48] in the GLP-1RA group versus 2.56 years [IQR: 3.89] in the comparator group).

RESULTS: In 157 880 matched patients (78 940 per group), GLP-1RA use was associated with a significantly lower risk of incident AMD (HR 0.82; 95% CI 0.68-0.98) compared with other weight-loss medications. Subtype analyses revealed reduced risk for unspecified AMD (HR 0.70; 95% CI 0.52-0.93) and a potential trend towards a lower risk of nonexudative AMD (HR 0.78; 95% CI 0.60-1.00; p = 0.050). Subgroup analyses suggested stronger effects in women and adults aged 60-69 years; all subgroup findings should be interpreted as exploratory.

CONCLUSIONS: GLP-1RA use is associated with a reduced risk of incident AMD-statistically significant for unspecified AMD, with a potential trend towards a lower risk of nonexudative AMD-in obese adults without diabetes. Whether this reflects direct GLP-1RA neuroprotective mechanisms, greater weight-loss magnitude or both remains to be determined. Further mechanistic research and prospective clinical trials are warranted.},
}

@article {pmid42186654,
year = {2026},
author = {Kar, SK and Nemivant, K and Sharma, UK and Priya, P and Abbasi, S and Yadav, NK},
title = {Transforming Eye-Care Diagnostics Through Artificial Intelligence, Biometric Evaluation, and Tele-Optometry.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107620},
pmid = {42186654},
issn = {2168-8184},
abstract = {Visual impairment remains a major global health concern associated with disorders such as diabetic retinopathy, glaucoma, cataract, and age-related macular degeneration. Early detection of ocular abnormalities remains essential for preventing irreversible visual loss. Conventional diagnostic methods rely on clinical examination and specialised imaging, yet limitations in accessibility, diagnostic variability, and delayed detection continue to affect effective eye-care delivery in many settings. Advances in digital technologies have introduced innovative diagnostic approaches integrating artificial intelligence (AI), ocular biometric evaluation, and tele-optometry to improve efficiency and reach of ophthalmic care. The objective of this review involves a comprehensive examination of recent developments in digital ophthalmic diagnostics, focusing on AI-based image analysis, biometric measurement technologies, and tele-optometry platforms. Relevant literature addressing AI applications, ocular biometric assessment, and remote ophthalmic screening systems was evaluated to synthesise current knowledge on diagnostic capability and clinical relevance. Current evidence indicates that AI algorithms enable automated interpretation of retinal images and facilitate early identification of ocular diseases. Biometric evaluation provides precise anatomical measurements that support refractive assessment and surgical planning. Tele-optometry systems expand diagnostic access through remote imaging and consultation services, improving screening coverage in underserved populations. Integration of AI, biometric technologies, and tele-optometry demonstrates strong potential to enhance disease detection, strengthen clinical decision support, and expand accessibility of ophthalmic diagnostic services.},
}

@article {pmid42187268,
year = {2026},
author = {Rynjah, H and Sarma, B and Parasar, K},
title = {Comment on "Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion".},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261445283},
doi = {10.1177/11206721261445283},
pmid = {42187268},
issn = {1724-6016},
}

@article {pmid42188557,
year = {2026},
author = {Judge, LW and Garcia-Carrillo, E},
title = {Combining Multisensory Cueing and Velocity-Based Training to Enhance Shot Put Performance in an F12 Para-Athlete: A Case Report.},
journal = {Sports (Basel, Switzerland)},
volume = {14},
number = {5},
pages = {},
doi = {10.3390/sports14050181},
pmid = {42188557},
issn = {2075-4663},
abstract = {This case report documents the multi-season development of a 38-year-old elite F12 shot putter with macular degeneration (<10% functional vision) who improved from 13.00 m to a personal best of 14.41 m between 2021 and 2023. Athletes classified as F11-F13 compete with significant visual impairment that limits spatial feedback during rotational tasks, yet longitudinal evidence describing integrated training frameworks remains scarce. A 12-month macrocycle integrated phase-dependent velocity-based resistance training using mean concentric velocity targets (0.70-1.00 m·s[-1]) monitored via linear position transducers with a 10% velocity loss threshold, combined with structured auditory and tactile cueing, including metronome pacing and environmental anchors. High-volume warm-ups and prehabilitation addressed a prior L4-L5 disk herniation. The athlete achieved 14.41 m at the 2023 U.S. Para Athletics Trials, with TrackMan[®]-verified release velocity of 11.3 m·s[-1]. Bench throw velocity improved by 35.4% (0.65 to 0.88 m·s[-1]) and squat jump velocity improved by 22.9% (1.18 to 1.45 m·s[-1]), while post-session RPE remained manageable, indicating improved neuromuscular readiness and training tolerance. No lumbar symptom recurrence occurred. This case illustrates that integrating velocity autoregulation, multisensory stabilization, and injury-informed preparation can support meaningful performance gains in visually impaired throwers and offers an applied framework for coaches working with F11-F13 athletes.},
}

@article {pmid42190107,
year = {2026},
author = {Kim, HM and Bae, Y and Kim, M and Lee, H and Chung, H},
title = {Systemic cancer risk profile in neovascular age-related macular degeneration: insights into shared aging-related mechanisms from a nationwide population-based study.},
journal = {Aging},
volume = {18},
number = {1},
pages = {593-604},
doi = {10.18632/aging.206383},
pmid = {42190107},
issn = {1945-4589},
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of vision loss in older adults and is increasingly recognized as a manifestation of systemic aging involving vascular and inflammatory pathways. Emerging evidence suggests that nAMD may also be linked to systemic diseases, including malignancies. Using data from the Korean National Health Insurance Service, we conducted a nationwide, population-based cohort study of 334,091 individuals (83,742 with nAMD and 250,349 matched controls) followed for up to 10 years. Patients with nAMD showed a modest but significant increase in overall cancer risk (adjusted hazard ratio [aHR], 1.084; P < 0.001), with selectively elevated risks for pancreatic (aHR, 1.155; P < 0.001), lung (aHR, 1.128; P < 0.001), thyroid (aHR, 1.241; P < 0.001), renal (aHR, 1.177; P = 0.002), bladder (aHR, 1.121; P = 0.002), and prostate (aHR, 1.085; P < 0.001) cancers. No significant associations were observed for other malignancies. These findings indicate that nAMD may serve as a clinical marker of systemic vulnerability to selected cancers, possibly through shared angiogenic, inflammatory, and polygenic mechanisms underlying aging-related disease susceptibility.},
}

@article {pmid42190237,
year = {2026},
author = {Lee, C and Karunainathan, MG and Zohalinejad, KD and Mæng, MO and Fabrin, NW and Yde, SK and Wykoff, CC and Abildgaard, SK and Vorum, H and Subhi, Y and Ørskov, M and Cehofski, LJ},
title = {Real-World Outcomes after Switch to Aflibercept 8 mg in Neovascular AMD: Twelve Months Follow-up on 654 Eyes.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004888},
pmid = {42190237},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate 12-month outcomes following systematic switch to aflibercept 8 mg in previously treated eyes with age-related neovascular macular degeneration (nAMD).

METHODS: Eyes in a plateau phase (≥10 prior anti-VEGF injections) that were switched to aflibercept 8 mg were retrospectively evaluated. Treatment intervals, best corrected visual acuity (BCVA), central retinal thickness (CRT), and data on intraretinal fluid (IRF) or subretinal fluid (IRF) were assessed at switch and after 3, 6, and 12 months.

RESULTS: In total, 654 eyes from 567 patients were included (mean [SD] age 82.4 [7.4], 34.5 [21.5] injections per eye before switch). The proportion of eyes with dry maculae increased from 55% at switch to 76% at 3 months (P<0.001), 73% at 6 months (P<0.001), and 69% at 12 months (P<0.05). Eyes treated at 3-5-week intervals declined from 46% to 18% at 12 months (P<0.001). Eyes on 9-12-week intervals increased from 11% to 34% (P<0.001). The mean treatment interval increased from 6.0 (2.1) to 7.8 (2.4) weeks (P<0.001). Eyes with dry maculae at switch were extended by 2.6 (1.8) weeks (P<0.001). The mean CRT decreased from 234.7 (49.7) to 223.5 (46.7) µm (P<0.001). BCVA declined from 68.5 (12.2) to 67.3 (13.9) ETDRS letters in the overall cohort, and from 68.5 (12.3) to 66.6 (14.3) ETDRS letters in eyes with a dry macula at switch (P < 0.001).

CONCLUSION: Switching to aflibercept 8 mg improved anatomical outcomes and reduced the proportion of eyes on short intervals. A slight decline in BCVA was observed, warranting long-term follow-up.},
}

@article {pmid42177487,
year = {2026},
author = {Simaku, E and Eddien, AN and Popa, M and Shafei, AE},
title = {Non-infectious occlusive retinal vasculitis following switching from aflibercept 2 mg to aflibercept 8 mg in neovascular age-related macular degeneration: a case report.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04953-z},
pmid = {42177487},
issn = {1471-2415},
abstract = {BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy represents the standard of care for neovascular age-related macular degeneration (nAMD). Aflibercept 8 mg was recently introduced with extended dosing intervals and favorable safety outcomes in phase III trials. Although no confirmed cases of occlusive retinal vasculitis were reported in pivotal studies, rare inflammatory vascular events may emerge during broader real-world exposure.

CASE PRESENTATION: A 74-year-old pseudophakic male with active nAMD in the left eye demonstrated significant anatomical and functional improvement following intravitreal aflibercept 2 mg. After switching to aflibercept 8 mg, the patient presented 26 days later with painful visual deterioration. Fundus examination revealed mild vitritis, segmental arterial sheathing, venous narrowing, and peripheral intraretinal hemorrhages. Fluorescein angiography demonstrated capillary non-perfusion and late vascular leakage. Optical coherence tomography confirmed cystoid macular edema. Extensive infectious and autoimmune investigations were negative. Systemic and local corticosteroid therapy resulted in regression of inflammation with partial visual recovery.

CONCLUSIONS: Non-infectious occlusive retinal vasculitis may rarely occur following switching to aflibercept 8 mg. Early recognition and prompt anti-inflammatory treatment are critical to minimize irreversible ischemic damage. Continued post-marketing pharmacovigilance is warranted.},
}

@article {pmid42177686,
year = {2026},
author = {Lains, I and Bhat, R and Mendez, K and Gil, J and Providencia, J and Barreto, P and Sourirajan, K and Kang, H and Nigalye, A and Miller, JB and Kim, I and Vavvas, D and Liang, L and Silva, R and Lasky-Su, J and Miller, JW and Husain, D},
title = {Association of age-related macular degeneration with exposome related metabolomics.},
journal = {Metabolomics : Official journal of the Metabolomic Society},
volume = {22},
number = {3},
pages = {},
pmid = {42177686},
issn = {1573-3890},
support = {K12EY016335/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; R01EY030088/GF/NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/metabolism/urine/blood ; *Metabolomics/methods ; Male ; Female ; Cross-Sectional Studies ; Aged ; Middle Aged ; *Exposome ; *Metabolome ; Aged, 80 and over ; Biomarkers/blood/urine ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a multifactorial disease, but it remains unclear how external exposures - the exposome - promote its development. Metabolomics can provide insights to better understand AMD pathophysiology. Previous work to date has focused primarily on associations between endogenous metabolites and AMD.

OBJECTIVES: This study aimed for the first time to investigate associations of exogenous metabolites in plasma and urine and AMD.

METHODS: Cross-sectional study including patients with AMD and a control group (> 50 years) from Boston, US and Coimbra, Portugal (PT). Color fundus photographs (CFP) of all participants were used for AMD staging. Fasting plasma and urine samples were used for metabolomic profiling using Ultrahigh Performance Liquid Chromatography - Mass Spectrometry (Metabolon, Inc). Multivariate and ordinal logistic mixed-effect regression models were computed for each cohort and then combined by meta-analysis. Primary outcome was association of metabolites with AMD (vs. no AMD). False discovery rate (FDR) was used to account for multiple comparisons and significant q-values are reported.

RESULTS: We included 1023 eyes (823 from the US and 580 from PT). Meta-analysis revealed significant associations of tartronate, thioproline and 2-methoxyhydroquinone sulfate levels with both presence and staging of AMD (q < 0.005 for all). Similar trends were seen in urine.

CONCLUSION: To the best of our knowledge, this is the first study to identify associations between exogenous metabolites and AMD. These findings are crucial for identifying possible targets for preventive strategies for this blinding disease.},
}

Humans
*Macular Degeneration/metabolism/urine/blood
*Metabolomics/methods
Male
Female
Cross-Sectional Studies
Aged
Middle Aged
*Exposome
*Metabolome
Aged, 80 and over
Biomarkers/blood/urine

@article {pmid42177934,
year = {2026},
author = {Gilead, N and Chong, YJ and Cheng, MFS and Kikushima, W and Sherif, M and George, L and Ong, C and Sun, C and Hong, CH and Ibrahim, FNI and Teo, KYC and Cheung, CMG},
title = {Predictors of 1-Year Visual Outcome in Central-Involving Submacular Hemorrhage Secondary to Neovascular AMD.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.05.035},
pmid = {42177934},
issn = {1879-1891},
abstract = {PURPOSE: To identify clinical and imaging predictors of 12-month visual outcome in patients with fovea-involving submacular hemorrhage (SMH) due to neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV).

DESIGN: Prospective observational clinical cohort study.

SUBJECTS: Asian patients with nAMD or PCV presenting with fovea-involving SMH.

METHODS: Between January 2016 and July 2024, eyes presenting with fovea-involving SMH ≥1 disc diameter with no evidence of blood organization were included. All patients received standard-of-care treatment. Clinical and multimodal imaging parameters were analyzed to identify predictors of visual outcome at 12 months.

MAIN OUTCOME MEASURES: Good (≤0.3 logMAR) and poor (≥1.0 logMAR) visual outcomes at 12 months.

RESULTS: Among 487 treatment-naïve eyes, 75 met inclusion criteria for fovea-involving SMH. Mean (SD) age was 71.40 (9.59) years, 74.4% were male, and 76.0% had PCV. Mean hemorrhage size was 18.92 (22.56) mm². All eyes received anti-VEGF therapy, 2.6% underwent additional pneumatic displacement, and 5.3% received photodynamic therapy. Best-corrected visual acuity (BCVA) improved from 1.04 (0.67) logMAR to 0.69 (0.62) at 12 months. 25 eyes (33.3%) achieved good visual outcome, while 22 eyes (29.3%) had poor visual outcome. On multivariable analysis, younger age (OR=0.47 per decade, 95% CI 0.26-0.86; P=0.02), better baseline BCVA (OR=0.87 per 0.1 logMAR, 95% CI 0.79-0.97; P<0.01), and thicker subfoveal choroid (OR=1.50 per 50 µm, 95% CI 1.07-2.10; P=0.02) independently predicted good visual outcome. Conversely, larger hemorrhage size predicted poor visual outcome (OR=1.04 per mm[2], 95% CI 1.01-1.07; P=0.02).

CONCLUSION: One-third of eyes with SMH achieved 0.3 logMAR (Snellen equivalent 20/40) or better vision. In addition to age, baseline BCVA, and hemorrhage size, we identified choroidal thickness as a biomarker associated with visual outcome.},
}

@article {pmid42179647,
year = {2026},
author = {Patel, MJ and Datta, M and Baredes, V and Fuentes-Gonzalez, T and Bass, S and Alba, D and Soloff, AC and Hackam, AS},
title = {Chronic exposure to aerosolized Arizona test dust reduces visual acuity in mice.},
journal = {Toxicology reports},
volume = {16},
number = {},
pages = {102263},
pmid = {42179647},
issn = {2214-7500},
abstract = {Air pollution is associated with increased incidence of age-related macular degeneration (AMD), glaucoma and other retinal diseases. The time course of molecular and cellular changes induced by chronic air pollution exposure that lead to retinal pathology are unknown. In this study, we investigated the effects of moderate levels of air pollution on visual acuity and retinal phenotypes in mice using Arizona test dust (ATD) as a surrogate for ambient air pollution. Mice were exposed to aerosolized standardized test dust for three hours a day, four days a week, for up to four months in a custom-built chamber. Controls were exposed to room air. Visual function was assessed using an optomotor assay and demonstrated reduced visual acuity after one month of exposure that persisted throughout the study. Rod and cone photoreceptors also showed temporarily decreased light-evoked responses that returned to normal levels by four months. Furthermore, reduced cone photoreceptors and retinal ganglion cells were observed whereas markers of retinal stress, including Iba1-positive microglia/macrophage and GFAP expression in macroglia, were not significantly elevated. Molecular analyses indicated elevated expression of genes in the Nrf2-ARE oxidative stress response pathway. Therefore, moderate levels of aerosolized ATD caused a persistent decline in visual acuity, mild retinal degeneration and transient functional changes. This study provides new information into the pathogenesis of pollution-induced retinal damage and establishes a new mouse model for investigating detrimental effects of moderate levels of air pollution in the retina.},
}

@article {pmid42179661,
year = {2026},
author = {Uzundede, T and Karatas, G and Yildiz, D and Cakir, A},
title = {The Comparison of Intracystic Hyperreflectivity in Different Macular Edema Etiologies. Is It a New Optical Coherence Tomography Biomarker?.},
journal = {Beyoglu eye journal},
volume = {11},
number = {1},
pages = {50-57},
pmid = {42179661},
issn = {2587-0394},
abstract = {OBJECTIVES: To detect the difference in internal hyperreflectivity of macular cystoid spaces in diabetic retinopathy (DR), exudative (wet) age-related macular degeneration (wet AMD), branch retinal vein occlusion (BRVO).

METHODS: The medical records of the consecutive patients who were followed up from Prof. Dr. Cemil Taşcıoğlu City Hospital, from 01 April 2023 to 01 June 2023, in the retina department, have been included in this study. The mean gray value (GV) and max-min GV parameters of the cystoid spaces which were detected in the spectral domain optical coherence tomography (OCT) scans, were measured by using the ImageJ program (National Institutes of Health, Bethesda, Maryland, USA). The established diagnosis, baseline best corrected visual acuities (BCVA), OCT biomarkers such as serous macular detachment, hard exudate, hyperreflective foci and central macular thicknesses were also noted. The parameters were compared to each other regarding the different pathologies.

RESULTS: The mean-max GV of cystoid spaces and the mean-max GV of cystoid/vitreous ratio were found to be highest in the DR, followed by BRVO, and lowest in wet AMD (p<0.001 and p<0.001; respectively). Correlation analyses revealed a positive correlation between OCT biomarkers and intracystic hyperreflectivity (ICH) (p<0.001, respectively). Besides, the max GV cystoid/vitreous ratio is positively correlated with the BCVA (p<0.046; p=0.04, respectively).

CONCLUSION: This pilot study investigates ICH in macular edema of various etiologies. The ICH was highest in the DR group, followed by the BRVO group, and lowest in the AMD group. It has been observed that there is a high correlation between ICH and OCT biomarkers. Findings support the hypothesis that ICH may reflect underlying inflammatory processes and contribute to individualized treatment approaches in retinal vascular pathologies.},
}

@article {pmid42179664,
year = {2026},
author = {Demir, U and Gunturkun, PN and Bozgul, P},
title = {Evaluation of the Association of Senile Macular Degeneration in Patients with Glaucoma.},
journal = {Beyoglu eye journal},
volume = {11},
number = {1},
pages = {42-49},
pmid = {42179664},
issn = {2587-0394},
abstract = {OBJECTIVES: The aim of the study was to evaluate the incidence of senile macular degeneration (SMD) in patients with primary open-angle glaucoma (POAG) and pseudoexfoliation glaucoma (PEG).

METHODS: The medical files of 2600 patients with glaucoma were analyzed. In this study, 168 patients (90 females and 78 males) with POAG and PEG were included. Patients diagnosed with POAG and PEG with SMD were also recorded. SMD was classified in two categories: Wet type and dry type. Lens status was classified as pseudophakic and phakic. Glaucoma severity was classified according to the Hodapp-Parrish-Anderson criteria. All patients underwent complete ophthalmologic examinations.

RESULTS: Ninety (53.57%) patients were female, and 78 (46.43%) were male. The mean age was 63±8.4 years for women and 66.5±7.8 years for men. Sixty-six (73.3%) of women and 60 (76.9%) of men had POAG, 24 (26.7%) of women and 18 (23.1%) of men had PEG. 18 (20.0%) right and 25 (27.8%) left eyes of women and 30 (38.5%) right and 24 (30.8%) left eyes of men were pseudophakic, 72 (80.0%) right and 65 (72.2%) left eyes of women and 48 (61.5%) right and 54 (69.2%) left eyes of men were phakic. SMD was observed in 10 patients (5.95%); four women and five men had dry-type SMD, while one man had wet-type SMD.

CONCLUSION: In our study, when gender, age, severity of glaucoma, pseudophakic and phakic status of the lens were evaluated in patients with the association of glaucoma and SMD, these variables had no statistically significant effect on the association of glaucoma and SMD.},
}