@article {pmid42038919,
year = {2025},
author = {Bokhary, KA},
title = {Narrative Review of Artificial Intelligence in Ophthalmic Disease Detection : Artificial Intelligence in Ophthalmic Diseases Detection.},
journal = {Galen medical journal},
volume = {14},
number = {},
pages = {e3979},
pmid = {42038919},
issn = {2322-2379},
abstract = {BACKGROUND: Artificial intelligence (AI) is revolutionizing ophthalmology and optometry by utilizing high-resolution imaging modalities such as optical coherence tomography (OCT), fundus photography, and corneal topography. These modalities generate quantifiable data suitable for machine learning (ML), facilitating automated diagnosis of ocular conditions like diabetic retinopathy, glaucoma, and age-related macular degeneration (AMD), which are leading causes of visual impairment worldwide. This narrative review evaluates the role of ML in improving diagnostic accuracy and accessibility in eye care, focusing on methodological complexities, supervised and unsupervised learning approaches, and challenges in clinical integration.

MATERIALS AND METHODS: A comprehensive narrative literature review was conducted, analyzing ML applications in ophthalmology.

RESULTS: AI systems exhibit high sensitivity and specificity, often outperforming human graders in diabetic retinopathy screening and early detection of glaucoma and AMD using OCT and fundus imaging. Anterior segment diseases benefit from AI-driven corneal topography analysis. Challenges include image quality, dataset imbalances, and variability in imaging protocols, necessitating fine-tuning for diverse clinical environments. Unsupervised learning shows potential for identifying novel biomarkers but requires further validation.

CONCLUSION: AI-driven ML models significantly enhance eye disease diagnostics, improving accuracy and accessibility, particularly in resource-limited settings. However, challenges like data standardization and model generalizability must be addressed to ensure robust clinical adoption.},
}

@article {pmid42038949,
year = {2026},
author = {Almusib, RBA and Awad, AH and Ghandorah, AM and AnbarSerry, AOM and Aljumah, HK and Albarrak, AI and Alghanmi, RM and Alshami, FME and Alhejaili, BFR and Alboqami, AFF and Mohayya, EMH and Almatrafi, AM and Alzuwayr, MA},
title = {Relationship of Atropine in Controlling Myopia Progression Among Pediatric Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {590501},
pmid = {42038949},
issn = {1177-5467},
abstract = {PURPOSE: Myopia is a refractive error where light focuses in front of the retina, causing blurred distance vision. It is linked to complications such as macular degeneration, retinal detachment, glaucoma, and cataracts, potentially resulting in irreversible vision loss. Controlling myopia progression is critical to reduce long-term impairment. This systematic review evaluate and compare different atropine concentrations for slowing myopia progression in pediatric patients.

PATIENTS AND METHODS: A comprehensive electronic search was conducted in PubMed, Google Scholar, Embase, and the Cochrane Central Register of Controlled Trials for studies published between June 1, 2006, and September 1, 2024. Included studies enrolled participants aged <18 years, used a randomized placebo-controlled design, and evaluated atropine effects on myopia progression in individuals with spherical equivalent ≤ 0.25 D. Primary outcomes, spherical equivalent refractive error (SER) and axial length (AL), were analyzed via meta-analysis using mean differences (MDs) with 95% confidence intervals (CIs).

RESULTS: This meta-analysis included 10 studies (2006-2024) evaluating atropine effects on myopia progression. Atropine significantly slowed progression versus placebo. At 6 and 12 months, MD in SER was 0.26 (95% CI, 0.17-0.34) and 0.54 (95% CI, 0.26-0.82), respectively, (p < 0.001). Atropine also significantly reduced AL growth at 6 months (MD -0.09, 95% CI, -0.14 to -0.04).

CONCLUSION: Atropine effectively reduced AL growth and myopia progression. Heterogeneity across studies suggests variability. Further research is essential to clarify its mechanism.},
}

@article {pmid42039586,
year = {2026},
author = {Ghosh, S and Koontz, V and Xin, Y and Bammidi, S and Meyer, D and Wang, H and Babu, VS and Dutta, P and Cherukaraveedu, D and Mohanakrishnan, SA and Mondal, AK and Das, J and Nguyen, J and Soundararajan, A and Adekale, IA and Bhaumik, D and Hose, S and Rowan, S and Pattabiraman, PP and Kannan, RM and Handa, JT and Yi, J and Sripathi, SR and Qian, J and Sinha, D},
title = {Gut-derived metabolic reprogramming drives immune aging and tissue degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.14.718497},
pmid = {42039586},
issn = {2692-8205},
abstract = {Aging is characterized by changes in gut microbiome, metabolic imbalance and chronic inflammation, yet how these processes integrate to drive tissue degeneration remains poorly defined. Using age-related macular degeneration (AMD) as a model of tissue aging, we identify a diet-induced metabolic-immune axis that promotes systemic and retinal degeneration. In mice, a high-fat, cholesterol-enriched (HFC) diet induced perturbations in the gut structural integrity and microbiome repertoire, as well as systemic metabolic aging signatures, prominently marked by reduced circulating histidine. Plasma histidine levels were similarly decreased in AMD patients and inversely correlated with body mass index (BMI) in control donors. These diet-induced gut microbiome changes and subsequent metabolic alterations promoted peripheral innate immune reprogramming, with expansion of inflammatory neutrophils and monocytes that infiltrated the outer retina in a mouse model. Mechanistically, the gut-derived IGF1R/AKT2 signaling acts as a central regulator of global epigenetic remodeling and systemic immune aging under high-fat conditions in C. elegans . In a mouse model with an age-dependent dry AMD-like pathology, distinct retinal pigment epithelium (RPE) subpopulations exhibited downregulation of the histidine transporter SLC7A5, linking metabolic stress to activation of MIF/CD74-dependent inflammatory signaling between RPE and infiltrating immune cells. Histidine supplementation or AKT2 phospho-state modulation attenuated systemic immune activation and rescued retinal degeneration. These findings identify histidine-axis dysregulation as a mechanistic bridge between diet-induced microbiome changes, metabolic stress, immune aging, and retinal degeneration.},
}

@article {pmid42040622,
year = {2026},
author = {Zhang, X and Cui, B and Liu, Y and Ji, X and Tian, X and Hou, S and Yang, L and Yang, J},
title = {Psychosocial determinants of anti-VEGF treatment adherence in AMD patients: optimization of one-stop intravitreal injection service model.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1745453},
pmid = {42040622},
issn = {2296-858X},
abstract = {OBJECTIVE: To investigate modifiable psychosocial determinants of anti-VEGF treatment adherence in patients with neovascular age-related macular degeneration (nAMD) and evaluate the optimization effects of a one-stop intravitreal injection service model.

METHODS: This historical control mixed-methods study included patients receiving anti-VEGF treatment at Cangzhou Regional Ophthalmology Center from August 2022 to October 2024. Patients were divided into three groups based on service models: traditional multiple-visit group (historical control, n = 165), one-stop standard group (n = 161), and one-stop AI-enhanced group (n = 162). The Hospital Anxiety and Depression Scale (HADS) was used to assess psychological status, and geographic information systems analyzed spatial accessibility impacts. Primary outcome measures included 12-month retention rate, early discontinuation rate (within 6 months), and appointment adherence rate. In-depth semi-structured interviews were conducted with patients from the one-stop standard and AI-enhanced groups, using thematic analysis to identify key influencing factors. Logistic regression analysis was used to analyze adherence predictors.

RESULTS: Compared to the historical control group, the one-stop standard and AI-enhanced groups showed significantly reduced clinic-to-injection time (23.87 vs. 6.47 vs. 6.01 h, P < 0.05), significantly improved 12-month retention rates (52.12 vs. 73.29 vs. 85.80%, P < 0.05), and significantly reduced early discontinuation rates (29.09 vs. 17.39 vs. 9.88%, P < 0.05). Regarding clinical outcomes, patients in the AI-enhanced group showed more significant best-corrected visual acuity (BCVA) improvement (logMAR change: -0.08 vs. -0.12 vs. -0.17, P < 0.05) and more pronounced central retinal thickness reduction (57.83 vs. 86.92 vs. 111.75 μm, P < 0.05). Multifactorial analysis showed that residential distance >38 km, baseline high anxiety levels, and baseline depressive symptoms were independent risk factors for treatment discontinuation. AI-enhanced intervention significantly reduced early discontinuation risk (P < 0.05). Qualitative analysis identified five main themes: treatment anxiety, service experience, expectation management, social support, and service improvement needs. Safety event incidence rates showed no significant differences between groups (P > 0.05).

CONCLUSION: The one-stop intravitreal injection service model significantly improved treatment adherence in nAMD patients, with AI-enhanced intervention further optimizing outcomes. Baseline anxiety and depression levels, along with geographic distance, are important modifiable determinants of treatment adherence. Personalized service models integrating psychosocial interventions provide new insights for precision management of chronic eye diseases.},
}

@article {pmid42040936,
year = {2026},
author = {Azargui, S and Lisker-Cervantes, A and Patnaik, JL and Gnanaraj, R and Mehta, N and Gange, B and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Mandava, N and Forest, TEC},
title = {Imaging Biomarkers To Predict Progression of Intermediate AMD with Avascular Pigment Epithelial Detachment in the University of Colorado AMD Registry.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-9193520/v1},
pmid = {42040936},
issn = {2693-5015},
abstract = {Purpose: To investigate whether specific imaging biomarkers predict progression to neovascular AMD (nAMD) or geographic atrophy (GA) in eyes with high-risk intermediate age-related macular degeneration (iAMD) and avascular pigment epithelial detachment (PED). Methods: Prospective longitudinal cohort study of eyes with iAMD and avascular PED from the University of Colorado AMD registry (August 2014 - August 2023) with ≥1 month of follow-up through February 2024. Multimodal imaging, including color fundus photos (CFP), fundus autofluorescence (FAF), and optical coherence tomography (OCT), was graded by two reviewers for presence of specific imaging biomarkers. Time-to-progression survival analysis was conducted with hazard ratios calculated. Results: Over a median follow-up period of 35 months, 224 eyes (142 patients) were included. 31 (13.8%) eyes progressed to nAMD, and 63 (28.1%) to GA. Progression to nAMD was significantly predicted by pigmentary changes on CFP (HR=4.43 (95%CI: 1.77, 11.1), p=0.001) and intraretinal hyperreflective foci (iHRF) on OCT (HR=4.90 (95%CI: 2.02, 11.9), p=0.0005). Progression to GA was significantly predicted by pigmentary changes on CFP (HR=3.60 (95%CI: 1.94, 6.67), p<0.0001), iHRF (HR=4.13 (95%CI: 2.14, 7.94), p<0.0001), acquired vitelliform lesions (AVL; (HR=2.97 (95%CI: 1.55, 5.68), p=0.001)) and incomplete retinal pigment epithelium and outer retina atrophy (iRORA; (HR=4.18 (95%CI: 1.52, 11.4), p=0.006)). No other biomarkers demonstrated significance. Conclusion: In eyes with avascular PED, pigmentary changes and iHRF were significantly associated with progression to nAMD and GA, while AVL and iRORA were specifically to GA. We highlight in this study important imaging biomarkers that help identify high-risk eyes that may warrant closer monitoring to ensure timely therapeutic intervention.},
}

@article {pmid42041185,
year = {2026},
author = {Ju, H and Jin, L and Qin, X and Tian, Y and Peng, H and Wang, X},
title = {Associations of Frailty Index and Composite Dietary Antioxidant Index With Major Ocular Diseases and Analysis of Component Contributions: A Cross-Sectional Study.},
journal = {Translational vision science & technology},
volume = {15},
number = {4},
pages = {25},
doi = {10.1167/tvst.15.4.25},
pmid = {42041185},
issn = {2164-2591},
mesh = {Humans ; Cross-Sectional Studies ; Male ; *Antioxidants/metabolism ; Middle Aged ; Female ; *Frailty/epidemiology ; *Eye Diseases/epidemiology ; Aged ; Nutrition Surveys ; *Diet ; Adult ; United States/epidemiology ; },
abstract = {PURPOSE: To evaluate the independent and joint effects of the frailty index (FI) and composite dietary antioxidant index (CDAI) with major ocular diseases and quantify contributions of their components.

METHODS: We analyzed 4455 U.S. adults aged ≥40 years from NHANES 2005-2008. Frailty was defined using a 49-item deficit accumulation FI (FI > 0.21 considered frail), and CDAI was derived from six antioxidants (carotenoids, vitamins A, C, E, selenium, zinc). Weighted multivariable logistic regression, variable importance, restricted cubic spline analyses, and sensitivity analyses assessed associations with retinopathy, cataract, diabetic retinopathy (DR), glaucoma, and age-related macular degeneration.

RESULTS: Higher FI was associated with higher odds of all major ocular diseases (any ocular disease: odds ratio [OR] = 1.35; DR: OR = 2.21; glaucoma: OR = 1.34), whereas higher CDAI was associated with lower odds (any ocular disease: OR = 0.97; glaucoma: OR = 0.91). Participants with high FI and low CDAI had the highest odds, based on predefined cutoff categories (any ocular disease: OR = 2.22; DR: OR = 4.92; cataract: OR = 2.50; glaucoma: OR = 3.18; all P < 0.05). Exploratory analyses showed that CDAI contributions varied by disease, whereas chronic disease burden dominated among FI domains.

CONCLUSIONS: Higher FI and lower CDAI were independently and in combination associated with major ocular diseases, highlighting the relevance of considering frailty status and dietary antioxidant profiles together in ocular health.

TRANSLATIONAL RELEVANCE: Higher FI and lower CDAI show combined associations with major ocular diseases, emphasizing their relevance to vision-related health.},
}

Humans
Cross-Sectional Studies
Male
*Antioxidants/metabolism
Middle Aged
Female
*Frailty/epidemiology
*Eye Diseases/epidemiology
Aged
Nutrition Surveys
*Diet
Adult
United States/epidemiology

@article {pmid42041592,
year = {2026},
author = {Yang, Y and Liu, P and Li, J and Deng, Y and Xiao, L and Peng, Q and Peng, J},
title = {Retinal Pigment Epithelium Ageing: Cellular and Molecular Mechanisms of Long-Term Homeostasis and Age-Related Dysfunction.},
journal = {Cells},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/cells15080725},
pmid = {42041592},
issn = {2073-4409},
support = {82274341, 82405487//National Natural Science Foundation of China/ ; 2024JJ5304, 2025JJ60633//Natural Science Foundation of Hunan Province/ ; 2024JK2122//Key Research and Development Program of Hunan Province/ ; 23A0278, 23B0346//Scientific research project of Hunan Provincial Department of Education/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/metabolism ; *Homeostasis ; *Aging/pathology/metabolism ; Animals ; Macular Degeneration/pathology/metabolism ; Mitochondria/metabolism ; *Cellular Senescence ; },
abstract = {The retinal pigment epithelium (RPE) is a long-lived, highly polarised epithelial monolayer that performs essential functions in retinal homeostasis, including outer blood-retina barrier maintenance, visual cycle activity, metabolic exchange, phagocytic clearance of photoreceptor outer segments, and regulation of oxidative and immune balance. Because RPE cells persist for decades under conditions of sustained oxidative, metabolic, and phagocytic stress, this tissue provides a valuable model for examining how long-lived post-mitotic cells preserve function over time and how age-related dysfunction emerges when that balance weakens. Although much of the current literature on RPE ageing has been shaped by age-related macular degeneration (AMD), age-dependent change in the RPE should not be understood solely as a preclinical stage of disease. Rather, the ageing RPE offers a broader framework for studying cellular maintenance under chronic physiological load. In this review, we synthesise current evidence on RPE ageing across four interrelated domains: structural remodelling, mitochondrial and metabolic imbalance, proteostatic and lysosomal burden, and chronic inflammatory dysregulation. Across these processes, ageing in the RPE is expressed less as widespread cell loss than as progressive decline in cellular organisation, buffering capacity, and functional precision. Structural irregularity, altered mitochondrial regulation, incomplete degradative clearance, and persistent low-grade inflammatory signalling together reduce the ability of the RPE to maintain long-term homeostasis and increase vulnerability to age-related retinal dysfunction. We further argue that ageing in the RPE is best understood not as abrupt failure of isolated pathways, but as gradual loss of system coherence among interacting homeostatic systems that remain active while operating under increasing constraint. This view helps integrate diverse cellular and molecular findings and highlights the RPE as an informative model for understanding ageing in long-lived post-mitotic tissues.},
}

Humans
*Retinal Pigment Epithelium/pathology/metabolism
*Homeostasis
*Aging/pathology/metabolism
Animals
Macular Degeneration/pathology/metabolism
Mitochondria/metabolism
*Cellular Senescence

@article {pmid41840594,
year = {2026},
author = {Liu, Y and Zhao, J and Huang, J and Qin, Y and Huang, Y and Fan, H and Zhou, W and Han, H and You, C and Cui, Z and Belfort Junior, R and Fernandes, RAB and Yan, H},
title = {Real-world cost evaluation of conbercept vs. ranibizumab for retinal and choroidal vascular diseases from 2021 to 2024: evidence from societal and medical insurance perspectives.},
journal = {BMC public health},
volume = {26},
number = {1},
pages = {},
pmid = {41840594},
issn = {1471-2458},
support = {22ZYYYQ05//Tianjin Medical University General Hospital Excellent Youth Science Fund/ ; 23JCQNJC01180//Tianjin Natural Science Foundation Youth Project/ ; 23JCZXJC00140//Beijing-Tianjin-Hebei Special Project/ ; 82530032，82330031//National Natural Science Foundation of China/ ; 25JCZDJC00390//Natural Science Foundation of Tianjin/ ; NO. TJYXZDXK-3-004A//The Tianjin Key Medical Discipline Construction Project/ ; },
abstract = {BACKGROUND: Retinal and choroidal vascular diseases including age-related macular degeneration (AMD), branch and central retinal vein occlusion (BRVO, CRVO), diabetic macular edema (DME), and choroidal neovascularization secondary to pathologic myopia (PM) are important causes of blindness. Their treatments by anti-VEGF agents imply heavy economic impact.

METHODS: The Markov model was constructed based on best-corrected visual acuity, real-world injection frequencies and medical costs of 15,266 patients in Tianjin (2021–2024), utility values, and transition probabilities derived from clinical trials. Costs and outcomes were calculated separately under societal and medical insurance perspectives. Incremental cost-effectiveness ratios (ICERs) were computed, and sensitivity analyses (one-way, two-way and probabilistic) were conducted to assess result robustness.

RESULTS: From both the societal and medical insurance perspectives, conbercept was more cost-effective than ranibizumab in BRVO, CRVO, DME, and PM with ICERs as -442,423.176, -2,429,628.701, -69,339.384, -410,661.276 as Chinese Yuan/quality-adjusted life year (RMB/QALY) under the societal perspective, and -370,506.503, -2,491,085.315, -66,253.162, -432,736.475 RMB/QALY under the medical insurance perspective in 2023, respectively. In contrast, ranibizumab consistently showed greater effectiveness for AMD, with conbercept’s ICER reaching 53,927.073 RMB/QALY in 2024 under the medical insurance perspective. Sensitivity analyses confirmed the robustness of these findings.

CONCLUSION: Conbercept is a cost-effective alternative to ranibizumab in RVO, DME, and PM from societal and medical insurance perspectives. In AMD, ranibizumab remains more clinically effective option. These findings provide economic evidence to support value-based decision-making anti-VEGF therapy in China.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12889-026-26994-1.},
}

@article {pmid42033410,
year = {2026},
author = {Gu, X and Terebuh, P and Xu, R and Kaelber, DC and Davis, PB},
title = {Age-related macular degeneration and dementia: Association through pathogenesis or visual impairment?.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261438849},
doi = {10.1177/13872877261438849},
pmid = {42033410},
issn = {1875-8908},
abstract = {BackgroundStudies suggest a link between blindness, age-related macular degeneration (AMD), and dementia risk, but whether this stems from AMD pathology or blindness remains unclear. This study examines the relationship between AMD and dementia.ObjectiveTo evaluate the association between AMD and 5-year dementia risk in non-blind patients.MethodsThis retrospective cohort study used TriNetX to compare non-blind patients with exudative AMD (n = 35,021) and non-exudative AMD (n = 96,809) to those without AMD (n = 1,801,879) for five-year dementia risk. Blind (n = 90,615) and non-blind (n = 800,737) patients were compared. Cohorts were propensity-matched for confounding factors.ResultsNon-blind AMD patients had decreased Alzheimer's disease risk, while blindness showed a strong positive association. Exudative AMD had HR of 0.84 (95% CI = [0.72, 0.97]), non-exudative AMD had HR of 0.95 (95% CI = [0.87, 1.04]), but blindness increased Alzheimer's disease risk (95% HR = 1.29, CI = [1.17, 1.41]).ConclusionsThese findings suggest that previously reported associations between AMD and dementia may be partially mediated by visual impairment. The modest reduction in dementia risk in non-blind AMD patients may reflect differences in healthcare utilization or treatment exposure among AMD patients.},
}

@article {pmid42033485,
year = {2026},
author = {Desmettre, T and Ledesma-Gil, G and Paques, M},
title = {Bidirectional Retro mode differential imaging improves drusen boundary depiction in early and intermediate AMD: a pilot study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42033485},
issn = {1435-702X},
}

@article {pmid42033607,
year = {2026},
author = {Zhang, R and Tunon-Robinson, I and Nguyen, AK},
title = {Visual Outcomes Following Infectious Endophthalmitis from Intravitreal Injections of Biologic Drugs: An Intelligent Research in Sight Registry Retrospective Analysis.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42033607},
issn = {2193-8245},
abstract = {INTRODUCTION: Intravitreal (IVT) injections are now among the most frequently performed intraocular procedures globally. Evidence regarding post-IVT-injection infectious endophthalmitis is primarily derived from a limited number of randomized controlled trials and retrospective case series. This study assesses visual acuity outcomes after IVT biologic therapy utilizing data from a large-scale ophthalmic registry, with the objective of elucidating the real-world effects of post-IVT-injection infectious endophthalmitis on patient visual function.

METHODS: Data were obtained from the Intelligent Research in Sight[®] (IRIS[®]) Registry, focusing on subjects who received commercially available IVT anti-VEGF and anti-complement biologic drugs.

RESULTS: As of 31 December 2024, 1,998,399 individuals received at least one IVT injection in one or both eyes, and 13,074 subjects (affecting 13,317 eyes) were diagnosed with infectious endophthalmitis. Incidence of infectious endophthalmitis per IVT injection was 0.052%. The cumulative rate of infectious endophthalmitis per subject rose from 0.31% after 10 IVT injections to 0.58% after 60 injections. The proportion of subjects who were legally blind (defined as ≤ 35 letters or ≤ 20/200) increased from 19.4% before the infectious endophthalmitis event to 46.1% afterward. In total, 94 eyes affected by infectious endophthalmitis underwent evisceration or enucleation. Subjects with retinal vein occlusion and myopic choroidal neovascularization had the highest incidence rates of infectious endophthalmitis compared with those with neovascular (wet) age-related macular degeneration and diabetic macular edema/diabetic retinopathy.

CONCLUSIONS: In the real world, the cumulative incidence of infectious endophthalmitis per subject is positively correlated with the total number of IVT injections administered. While the incidence of post-IVT-injection infectious endophthalmitis was comparable to literature values reported after cataract surgery, visual acuity outcomes were worse in the post-IVT injection group. Implementing strategies aimed at reducing IVT injection frequency may have the potential to lower the incidence of infectious endophthalmitis and the consequent risk of significant vision loss.},
}

@article {pmid42033608,
year = {2026},
author = {Haase, M and Wittenborn, E},
title = {Rapid Effects on Anatomical and Functional Outcomes following Upload with Faricimab in Treatment-Naïve nAMD: German Single-Center Study 45DRY.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42033608},
issn = {2193-8245},
abstract = {INTRODUCTION: The bispecific antibody faricimab inhibits vascular endothelial growth factor A (VEGF-A) and angiopoietin-2 (Ang-2), two key mediators in the pathophysiology of neovascular age-related macular degeneration (nAMD), which is characterized by choroidal neovascularization, vascular instability, leakage, and intra/subretinal fluid with consequent vision loss. The aim of our study was to assess the effectiveness of faricimab at week 16 versus baseline in patients with treatment-naïve nAMD managed under real-world conditions in Germany.

METHODS: 45DRY was a retrospective, single-center analysis of consecutive patients with treatment-naïve nAMD initiating faricimab (four monthly injections at weeks 0, 4, 8, and 12). Outcomes were evaluated at baseline and week 16 (± 14 days). The primary endpoint was change from baseline in central retinal thickness (CRT); secondary endpoints were change in best-corrected visual acuity (BCVA) and presence/absence of intraretinal fluid (IRF), subretinal fluid (SRF), combined IRF + SRF, and subretinal pigment epithelium (sub-RPE) fluid. Analyses were descriptive.

RESULTS: A total of 45 eyes from 45 patients were included (mean age 82.1 years; 51.1% female). Mean CRT decreased by -140.8 μm from 343.1 µm at baseline to 202.4 µm at week 16 [95% confidence interval (CI) -178.2 to -103.3]. Mean BCVA improved by -0.15 logMAR at week 16. Among eyes with retinal fluid at baseline, IRF resolved in 100% (24/24), SRF in 94.1% (32/34), combined IRF + SRF in 100% (17/17), and sub-RPE fluid in 90% (9/10). Maintenance of fluid-free status was universal in eyes negative at baseline for IRF (21/21), SRF (11/11), and combined IRF + SRF (28/28); sub-RPE fluid remained absent in 100% (35/35).

CONCLUSIONS: In routine clinical practice, a four-dose faricimab upload per label at the time of study conduct led to a rapid and substantial anatomical drying effect at week 16 with improvement in BCVA and marked CRT reduction. These real-world findings confirm that faricimab rapidly and effectively reduces retinal fluid, in line with post hoc analyses of the pivotal TENAYA and LUCERNE trials.},
}

@article {pmid42036126,
year = {2026},
author = {Turnbull, PRK and Acosta, ML and Lee, A and Solanki, B},
title = {Optometrist attitudes towards delivering intravitreal injections in Aotearoa New Zealand.},
journal = {Clinical & experimental optometry},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/08164622.2026.2652580},
pmid = {42036126},
issn = {1444-0938},
}

@article {pmid42027463,
year = {2026},
author = {Drago, L and De La Motte, LR},
title = {The eye's coral reef: toward a planetary-health agenda for ocular-microbiome stewardship.},
journal = {Frontiers in microbiology},
volume = {17},
number = {},
pages = {1816460},
pmid = {42027463},
issn = {1664-302X},
abstract = {Coral reefs and the human ocular surface represent ecologically distinct yet structurally comparable microbial ecosystems in which resilience depends on finely regulated host-microbe interactions. In coral reef science, microbial shifts precede visible bleaching and ecosystem collapse, enabling the development of predictive stress indices such as Degree Heating Weeks (DHW). Comparable principles are emerging in host-associated, low-biomass microbiomes, where subtle perturbations may trigger disproportionate functional consequences. Here, we propose a systems-level conceptual framework linking coral reef holobionts and the ocular surface as sentinel ecosystems governed by cumulative stress, threshold dynamics, and microbial instability. We introduce two heuristic constructs-the Cumulative Desiccating Load (CDL) and the Ocular Dysbiosis Sentinel Index (ODSI)-to frame dysbiosis as a trajectory of resilience loss driven by cumulative perturbations. Aging-related conditions such as age-related macular degeneration are discussed as examples of microbial and metabolic senescence within the human holobiont, conceptually paralleling coral reef decline under chronic sublethal stress. By integrating environmental and host-associated microbiome research within a planetary-health perspective, this article advances a resilience-oriented systems framework applicable across biological scales.},
}

@article {pmid42027954,
year = {2026},
author = {Li, J and Yan, Z and Mao, D and Liu, X and Lee, P and Lyu, Y and Feng, N},
title = {Microneedle technology in the treatment of ocular diseases: Advances and applications.},
journal = {Asian journal of pharmaceutical sciences},
volume = {21},
number = {2},
pages = {101129},
pmid = {42027954},
issn = {2221-285X},
abstract = {Microneedle (MN) technology has emerged as a transformative approach for treating ocular diseases, addressing the limitations of conventional drug delivery methods such as low bioavailability and poor patient compliance. This review highlights the advancements and applications of MNs in managing both anterior and posterior segment ocular diseases. MNs overcome physiological barriers, enabling precise, minimally invasive drug delivery with enhanced efficacy. Various MN designs, such as solid, coated, soluble, hollow, hydrogel and cryo-MNs, are tailored for specific therapeutic needs, offering rapid or sustained drug release. Applications include treating keratitis, glaucoma, age-related macular degeneration and diabetic retinopathy, demonstrating improved drug penetration and reduced side effects. Despite challenges in manufacturing and clinical translation, MN technology holds promise for revolutionizing ocular therapeutics through innovations in materials, design, and personalized medicine.},
}

@article {pmid42028099,
year = {2026},
author = {Shah, SH and Zhu, Y and Bennett, C and Tracy, J and Ploumi, I and Barton, KM and Gumustop, S and Nodecker, K and Wagner, S and Chen, C and Ding, X and Stevanovic, M and Lains, I and Miller, JB},
title = {Standardized Ultra-Widefield Swept-Source OCT Imaging: A Reproducible Protocol for Peripheral Retinal Assessment.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {581561},
pmid = {42028099},
issn = {1177-5467},
abstract = {BACKGROUND: The utilization of ultra-widefield (UWF) photography and, more recently, UWF-OCT has increased greatly in retina clinic. The most widely available UWF-OCT uses navigated swept-source OCT (SS-OCT), which lacks a standardized protocol, consequently limiting comparisons across patient visits or larger population-based studies. We present a structured imaging protocol to address this limitation.

TECHNIQUE: A universal template standardizes the number, type, and anatomical positioning of seven scans per patient, including three 21 mm line scans and four UWF volume scans. Scans are automatically positioned per protocol and ultimately stitched into a composite image, which is optimized for longitudinal and inter-patient comparisons.

DISCUSSION: This protocol enhances efficiency and ensures reproducible assessment of peripheral retinal findings. It may be adapted for other UWF systems and is currently being evaluated for clinical applications.},
}

@article {pmid42028334,
year = {2026},
author = {Wang, WX and Wang, CC and Hsu, WC and Peng, YJ},
title = {From Supplements to Sight: Quantifying the Impact of Lutein and Carotenoid on Age-Related Macular Degeneration-A Systematic Review and Meta-Analysis of Randomized Controlled Trials.},
journal = {Journal of ophthalmology},
volume = {2026},
number = {},
pages = {2155378},
pmid = {42028334},
issn = {2090-004X},
abstract = {PURPOSE: To quantify the effects of lutein-containing supplementation on structural and functional visual outcomes in patients with age-related macular degeneration (AMD), with particular focus on disease stage and treatment exposure.

METHODS: A meta-analysis of randomized, placebo-controlled trials was conducted. Nine RCTs involving 860 participants were included. Eligible studies evaluated oral lutein alone or in combination with zeaxanthin or epilutein and reported pre- and post-treatment measurements of macular pigment optical density (MPOD) and best-corrected visual acuity (BCVA). Random-effects models were applied to calculate pooled effect sizes using Hedges' g. Subgroup and meta-regression analyses were performed to explore stage-specific responses and dose-duration associations.

RESULTS: Across the 9 RCTs, lutein-containing supplementation significantly improved MPOD (Hedges' g = -0.589, p < 0.001) and BCVA (Hedges' g = -0.827, p = 0.001). Improvements were predominantly observed in early-stage AMD, whereas no statistically significant benefit was detected in late-stage disease. Lutein monotherapy demonstrated greater visual benefit than combination regimens. Meta-regression analyses revealed significant positive associations between treatment effect and both supplementation duration and total lutein exposure. Contrast sensitivity and serum lutein concentrations also improved significantly.

CONCLUSION: Lutein-based supplementation is associated with measurable structural and functional visual benefits in early-stage AMD. Treatment effects appear dose- and duration-dependent, while evidence in late-stage AMD remains limited. These findings support early intervention strategies and warrant further investigation into long-term therapeutic impact.},
}

@article {pmid42029948,
year = {2026},
author = {Labishetty, SC and Kumar, N and Kumari, S},
title = {Comment on "Conjunctival microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion".},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261445275},
doi = {10.1177/11206721261445275},
pmid = {42029948},
issn = {1724-6016},
}

@article {pmid42030193,
year = {2026},
author = {Molins, B and Nabaes Jodar, MS and de Oliveira, E and Estanyol, JM and Peña, E and Bezunartea, J and Hernández, M and Figueras-Roca, M and Adan, A},
title = {Decellularized Aged Bruch's Membrane Confers Unique Biochemical Cues to Retinal Pigment Epithelium for In Vitro Modeling of Age-Related Macular Degeneration.},
journal = {Aging cell},
volume = {25},
number = {5},
pages = {e70501},
doi = {10.1111/acel.70501},
pmid = {42030193},
issn = {1474-9726},
support = {PI22/00782//Instituto de Salud Carlos III/ ; //Novartis Farmacéutica/ ; },
mesh = {Humans ; *Bruch Membrane/metabolism/pathology ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/pathology/metabolism ; Aged ; *Models, Biological ; Male ; Female ; Proteomics ; },
abstract = {Age-related macular degeneration (AMD), a chronic inflammatory disease, is a major cause of irreversible blindness worldwide. It involves the degeneration of the retinal pigment epithelium (RPE) and the accumulation of deposits between the RPE and the Bruch's membrane (BrM), ultimately leading to photoreceptor death. The multifactorial and chronic nature of AMD makes it challenging to model in vitro. We developed a biomaterial based on decellularized BrM (dECM-BrM) from aged donors to evaluate its ability to induce an AMD-like phenotype in RPE monolayers. BrM from 5 young and 5 aged human donors was decellularized and the protein profile analyzed by LC-MS/MS. dECM-BrM was then used as a coating substrate for RPE culture. A total of 281 proteins were identified and proteomic analysis screened 49 differentially expressed proteins in aged dECM-BrM. Gene Ontology analysis showed that they were associated with extracellular region, antioxidant activity, lipid metabolism and transport. Moreover, the KEGG pathway related to complement and coagulation cascade was significantly enriched. RPE culture on aged dECM-BrM allowed RPE polarization and after 60 days, transepithelial electrical resistance significantly decreased compared to RPE grown on young dECM-BrM, accompanied by increased IL-33 secretion and marked expression of drusen components such as vitronectin and apolipoprotein E, lipid deposition and complement factors C3 and C9. We showed a successful approach to obtain a BrM mimic based on decellularized BrM that ensured cellular removal while preserving ECM structure and identified differentially expressed proteins in aged dECM-BrM that may provide specific biochemical cues fundamental to model AMD in vitro.},
}

Humans
*Bruch Membrane/metabolism/pathology
*Retinal Pigment Epithelium/metabolism/pathology
*Macular Degeneration/pathology/metabolism
Aged
*Models, Biological
Male
Female
Proteomics

@article {pmid42030962,
year = {2026},
author = {Beiner, D and Zhu, H and Bosholm, CC and Wang, HC and Criswell, T and Atala, A and Ma, JX and Zhang, Y},
title = {Derivation and characterization of retinal pigment epithelium from urine-derived iPSCs.},
journal = {FEBS open bio},
volume = {},
number = {},
pages = {},
doi = {10.1002/2211-5463.70246},
pmid = {42030962},
issn = {2211-5463},
support = {NIH/HIAID R21 AI152832//National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH)/ ; NIH/NEI R21 EY0358332024//National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID, NIH)/ ; R03 AI165170/AI/NIAID NIH HHS/United States ; 2024 Pilot Research Grant//Eye Bank Association of America (EBAA)/ ; HT94252510856//Department of Defense/ ; 2025 Ignition Fund Pilot Award//Wake Forest School of Medicine (WFSM)/ ; 2025 Translational Team Science Pilot Award//Translational Eye and Vision Research Center (TrEVR), Wake Forest School of Medicine (WFSM)/ ; },
abstract = {Age-related macular degeneration (AMD), particularly its dry form, is a leading cause of irreversible vision loss due to retinal pigment epithelium (RPE) dysfunction and loss. Addressing this unmet therapeutic need requires non-invasive strategies for generating patient-specific RPE cells. This study reports the successful generation and initial characterization of RPE cells derived from urine-derived induced pluripotent stem cells (u-iPSC-RPE). Urine-derived stem cells (USCs) were isolated from healthy individuals and comprehensively characterized, confirming strong expression of renal progenitor makers and mesenchymal stem cell markers, while lacking standard hematopoietic markers. USCs were reprogrammed into iPSCs using the integration-free Sendai virus expressing the Yamanaka factors. The reprogrammed u-iPSC clones displayed characteristic pluripotency marker expression and demonstrated clearance of the Sendai virus by later passages. Subsequently, these u-iPSCs were efficiently differentiated into RPE cells, exhibiting characteristic hexagonal morphology and pigmentation which was confirmed by the expression of key RPE-specific proteins. Our findings demonstrate the feasibility and reliability of generating patient-specific u-iPSC-RPE cells from readily accessible USCs providing a foundation for future studies to investigate their functional potential for retinal disease modeling and therapeutic applications for AMD.},
}

@article {pmid42031005,
year = {2026},
author = {Palakkan, AA and Shankar, G and Vignesh, TP and Kim, R},
title = {A tunable, biofabricated light-delivery platform for in vitro modelling of age-related macular degeneration using iPSC-derived RPE cells.},
journal = {Biomedical materials (Bristol, England)},
volume = {},
number = {},
pages = {},
doi = {10.1088/1748-605X/ae6498},
pmid = {42031005},
issn = {1748-605X},
abstract = {The lack of physiologically relevant and controllable experimental systems has limited mechanistic understanding of age-related macular degeneration (AMD) and the development of effective therapeutic strategies. Here, we present a tunable in vitro retinal pigment epithelium (RPE) stress model that integrates engineered light delivery with lipid modulation to reproduce early AMD-like cellular pathology under standard culture conditions. Human RPE cells (ARPE-19 and iPSC-derived RPE) were exposed to precisely controlled, low-intensity light-induced oxidative stress in the presence of docosahexaenoic acid (DHA), a highly unsaturated retinal lipid, or palmitic acid (PA) as a saturated lipid control. Cellular responses were assessed using functional and structural readouts including lysosomal and mitochondrial activity, membrane integrity, epithelial morphology, tight junction organization, and lipid peroxidation. A programmable LED-based exposure system enabled fine control over light intensity, duration, and cycling, allowing delivery of sub-lethal, chronic oxidative stress. Combined light and DHA exposure selectively induced lipid peroxidation, disruption of ZO-1-defined tight junctions, and progressive loss of RPE viability, while PA-treated cells and non-retinal HuH7 hepatocytes showed minimal sensitivity. ARPE-19 cells responded rapidly, whereas iPSC-derived RPE cells exhibited delayed but comparable pathological changes, reflecting differences in cellular maturity and stress resilience. Pharmacological inhibition of ferroptosis using ferrostatin-1 significantly reduced lipid peroxidation and rescued epithelial integrity and cell viability, identifying ferroptosis as a key mechanism underlying RPE vulnerability in this system. By enabling programmable and reproducible delivery of oxidative lipid stress, this modular light-based platform provides a biofabrication-compatible framework for modeling early AMD, with potential for integration into more complex retinal constructs, co-culture systems, and high-throughput therapeutic screening pipelines.},
}

@article {pmid42031134,
year = {2026},
author = {Anegondi, N and Lam, D and Guymer, RH and Steffen, V and Cukras, CA and Ferrara, D and Wu, Z},
title = {Vision-Related Quality of Life in Geographic Atrophy: Association with Topographic Lesion Distribution.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.04.019},
pmid = {42031134},
issn = {1549-4713},
abstract = {PURPOSE: To understand the associations between the topographic lesion distribution and vision-related quality of life (VR-QoL) in individuals with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

DESIGN: Analysis of data from Chroma (NCT02247479) and Spectri (NCT02247531), which are two identically designed Phase III clinical trials of lampalizumab.

PARTICIPANTS: Eight-hundred and fifty-six participants that were ≥50 years old with bilateral GA who completed the National Eye Institute Visual Function Questionnaire 25 (NEI VFQ-25) at baseline.

METHODS: The NEI VFQ-25 was used to determine estimates of VR-QoL in the visual functioning (NEI VFQ-VF) domain, using calibrated item measures and rating category thresholds from Rasch analysis. GA were automatically segmented on combined fundus autofluorescence and near-infrared reflectance images, and its extent in central regions across varying diameters (from 0.25- to 6.00-mm, in 0.25-mm intervals) relative to the fovea were then derived.

MAIN OUTCOME MEASURES: Association between NEI VFQ-VF person measures and the minimum eye-level GA extent in the region evaluated within an individual (referred to as the minimum GA extent).

RESULTS: Minimum GA extent within the central region across varying diameters between 0.25- to 6.00-mm were all significantly associated with the NEI VFQ-VF person measures (P ≤ 0.001 for all), but the highest proportion of variance explained was seen when evaluating the central 2.50-mm diameter region (R[2] = 0.11). A multivariable analysis showed that only the minimum GA extent within the central 2.50-mm region (P < 0.001), but not the 2.50- to 6.00-mm annulus (P = 0.541), was independently associated with NEI VFQ-VF person measures.

CONCLUSIONS: In this cohort, VR-QoL is most strongly associated with minimum eye-level GA extent within the central 2.50-mm region within an individual. These findings underscore the importance of evaluating GA extent in this region, beyond simply considering foveal GA involvement, when seeking to evaluate structural changes most closely associated with self-reported impairments in visual functioning.},
}

@article {pmid42031505,
year = {2026},
author = {Jonas, JB and Panda-Jonas, S and Pan, Z and Xu, J and Jonas, RA and Wang, YX},
title = {Prevalence and associations of intraretinal hyperreflective foci in age-related macular degeneration: the Beijing Eye Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328004},
pmid = {42031505},
issn = {1468-2079},
abstract = {BACKGROUND: To assess prevalence and associations of intraretinal hyperreflective foci (HRFs) in a general population.

METHODS: Participants of the population-based Beijing Eye Study underwent optical coherence tomography and macula photography.

RESULTS: The study cohort included 1641 eyes (mean age: 62.8±9.1 years; range: 50-93 years). Prevalence of any HRF or HRFs located only above the ellipsoid zone (EZ) increased from 33/590 (5.6%; 95% CI 4.0 to 7.0) and 22/590 (3.7%; 95% CI 2.2 to 5.2), respectively, in normal eyes to 371/725 (51.2%; 95% CI 47.7 to 54.7) and 246/725 (33.9%; 95% CI 30.4 to 37.4), respectively, in eyes with early age-related macular degeneration (AMD), to 283/314 (90.1%; 95% CI 87.1 to 93.1) and 260/314 (82.8%; 95% CI 78.8 to 86.8), respectively, in eyes with intermediate AMD, and to 12/12 (100%) and 12/12 (100%), respectively, in late AMD. HRFs above the EZ were spatially associated with EZ defects in 298/540 (55.2%) eyes and external limiting membrane (ELM) defects in 203/540 (37.6%) eyes. 52 (96%) of 54 eyes with macular hyperpigmentations showed HRFs above the EZ, and 52 (9.6%) of 540 eyes with HRFs above the EZ had corresponding macular hyperpigmentations. Higher HRF prevalence was associated (multivariable analysis) with higher AMD stage (OR: 1.75; 95% CI 1.36 to 2.26; p<0.001), and higher prevalences of EZ defects (OR: 36.6; 95% CI 8.56 to 157; p<0.001), reticular pseudodrusen (OR: 1.91; 95% CI 1.29 to 2.82; p<0.001), retinal pigment epithelium (RPE) elevations (OR: 34.5; 95% CI 10.4 to 111; p<0.001) and interdigitation zone thinnings (OR: 4.22; 95% CI 1.90 to 9.35; p<0.001).

CONCLUSIONS: The HRF prevalence was relatively high in early AMD and increased to late AMD. HRF location and shape suggested intraretinally migrated RPE cells as their equivalent. The majority of HRFs were not associated with an ophthalmoscopically detected macular hyperpigmentation. HRFs can also be found in locations with a localised interdigitation zone thinning with spatially corresponding EZ defects and ELM defects.},
}

@article {pmid41933583,
year = {2026},
author = {Zhou, Y and Liu, Y and Chen, H and Yu, Y and Li, Y and Sun, Z and Han, X and Li, H and Zou, X and Sui, R},
title = {Expanding the Clinical and Genetic Spectrum of TTLL5-Associated Retinal Dystrophy: A Single-Center Cohort Study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.03.017},
pmid = {41933583},
issn = {2468-6530},
abstract = {PURPOSE: To characterize the clinical and genetic spectrum of TTLL5-related retinal dystrophy.

DESIGN: Retrospective observational study.

SUBJECTS: Twenty-one affected individuals from 19 unrelated families carrying biallelic TTLL5 variants.

METHODS: Patients with inherited retinal dystrophy and confirmed biallelic TTLL5 variants were retrospectively reviewed. Genetic diagnosis was established using whole-exome sequencing followed by Sanger confirmation and cosegregation analysis. Clinical assessments included best-corrected visual acuity, multimodal retinal imaging, visual field testing, and full-field electroretinography.

MAIN OUTCOME MEASURES: Visual function, retinal structural and functional characteristics, and genotype-phenotype correlation.

RESULTS: The cohort included 10 males and 11 females, aged 6 to 66 years. Based on phenotypic classification, 2 patients were diagnosed with cone dystrophy (CD), 12 with cone-rod dystrophy (CRD), and 7 with rod-cone dystrophy (RCD). Best-corrected visual acuity ranged from 0 to 2.70 logarithm of the minimum angle of resolution (LogMAR) (median, 0.6 LogMAR; interquartile range, 1.55) and was significantly correlated with age (Spearman R = 0.704; P < 0.001). All patients were myopic, with spherical equivalent values ranging from -1.13 to -18.00 diopters, and 14 of 21 (66.67%) had bilateral high myopia (≤-6.0 diopters). Retinal involvement was characterized by macular degeneration with progressive extension beyond the posterior pole. Fundus autofluorescence demonstrated parafoveal or macular hyperautofluorescent rings followed by expanding hypoautofluorescent areas, whereas OCT revealed parafoveal-to-diffuse disruption or loss of the ellipsoid zone with outer nuclear layer thinning. Genetic analysis identified 24 pathogenic variants, of which 19 (79.17%) were novel. The recurrent missense variant c.437G>A (p.Gly146Glu) was the most frequent allele in this cohort and was consistently associated with a CRD phenotype. Extraocular manifestations were uncommon, with sensorineural hearing loss observed in 1 patient.

CONCLUSIONS: TTLL5-associated retinal dystrophy exhibits a broad clinical spectrum encompassing CD, CRD, and RCD, with a high prevalence of myopia as a shared feature. The recurrent p.Gly146Glu variant showed a consistent association with the CRD phenotype, suggesting specific allele-phenotype correlations. These findings expand the recognized phenotypic and genetic spectrum of TTLL5-related disease and provide an important clinical framework for diagnosis, counseling, natural history, and future therapeutic studies.

FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.},
}

@article {pmid42021400,
year = {2026},
author = {Kniggendorf, V and Silveira, TC and Costa, VDM and Soriano, DS and Regatieri, CV and Sugai, RF and Bordon, A and Nutels, GS and Peixoto, AL and Moreira-Neto, CA and Miranda, JVC and Nehemy, MB and Damico, FM and Zacharias, LC and Lavinsky, D and Machado, CG and Veloso, CED and Cyrino, FV and Cella, W and Roisman, L and Brasil, OF and Andrade, GC and Stefanini, F and Malerbi, FK and Penha, FM and , },
title = {Real-world performance of faricimab for neovascular age-related macular degeneration and diabetic macular edema: experience from the BrazilRetNet multicenter study. Report 1.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00860-z},
pmid = {42021400},
issn = {2056-9920},
}

@article {pmid42021792,
year = {2025},
author = {Iztleuov, M and Abugaliyeva, N and Ryzhkin, S and Iztleuov, Y and Saparbaev, S and Smagulova, G},
title = {Current Insights into Plausible Mechanisms of Chromium (VI) Neurotoxicity in the Brain and Future Perspectives.},
journal = {Medical journal of the Islamic Republic of Iran},
volume = {39},
number = {},
pages = {157},
pmid = {42021792},
issn = {1016-1430},
abstract = {BACKGROUND: Hexavalent chromium (Cr (VI)) is a known neurotoxin and environmental contaminant. Despite its recognition, the underlying mechanisms by which Cr (VI) induces neurological damage remain insufficiently explored. The complexities of the Central Nervous System (CNS), including the Blood Brain Barrier (BBB) and supporting brain cells, contribute to regions-specific susceptibility within the brain. Understanding Cr (VI) neurotoxicity is crucial for its potential role in neurodegenerative diseases.

METHODS: A Systematic Review was conducted using international databases (PubMed, Medline, Scopus, and Web of Science) and Google Scholar. Only open-access, free full-text articles published in English between 2010 and 2025 were included. Following PRISMA 2020 guidelines, a total of 19 relevant studies were selected, comprising 12 animal-based and 7 human cohort studies.

RESULTS: Animal studies investigated the effects of Cr (VI) via various administration methods and doses, revealed evidence of oxidative stress, inflammatory markers, and apoptotic changes in the brain. Interventional studies showed delayed toxicity when antioxidant agents were used prior to Cr (VI) exposure, including PDC (Potassium Dichromate), SA (Sodium Alginate), and TNG (Tangeretin). Human studies, including autopsies and cell culture analyses, demonstrated neurotoxic effects in conditions such as ALS (Amyotrophic Lateral Sclerosis), nAMD (Neovascular Age-Related Macular Degeneration).

CONCLUSION: Animal studies have clarified the role of oxidative stress in Cr (VI)-induced neurotoxicity. Human cohort studies have identified Cr (VI) as an environmental risk factor for both neurodegenerative and neurobehavioral disorders. Future research should focus on defining harmful levels of Cr (VI) and exploring potential antioxidant therapies.},
}

@article {pmid42022797,
year = {2026},
author = {Sannan, NS and Ramadan, M and Malli, I and Ishgi, L and Al Johani, R and Abualjamal, R},
title = {Frequency and comorbidities of age-related macular degeneration in KSA: A retrospective multiregional study.},
journal = {Journal of Taibah University Medical Sciences},
volume = {21},
number = {3},
pages = {411-419},
pmid = {42022797},
issn = {1658-3612},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. In this study, we characterized the frequency of AMD and its comorbidities in understudied regions.

METHODS: A retrospective cohort study was conducted using medical records from tertiary care hospitals in KSA (2016-2022). Patients aged ≥40 years with a confirmed AMD diagnosis were included. Demographic and clinical data were analyzed, including comorbidities. Logistic regression analyses were performed.

RESULTS: Among the 335 patients diagnosed, 66.9% had the exudative form and 33.1% had the non-exudative form. The cohort had a mean age of 71.17 ± 10.12 years, and there was no significant difference in age between AMD subtypes (p = 0.29). High prevalences of diabetes (66.3%) and hypertension (65.1%) were observed. Estimation of annual case counts revealed a significant temporal variation in diagnosed AMD cases, peaking in 2019 and increasing again by 2021-2022. Logistic regression identified female gender (Exp(B) = 1.03; p = 0.009) and age at diagnosis of diabetes mellitus (Exp(B) = 0.93; p < 0.001) as significant predictors of age at AMD onset. Diabetes mellitus was independently associated with later AMD diagnosis (Exp(B) = 1.03; p = 0.02). Conversely, stroke history was linked to earlier AMD onset (Exp(B) = 0.94; p = 0.002). Other comorbidities, including hypertension, dyslipidemia, and heart failure, had no significant associations.

CONCLUSION: Our findings highlight the burden of AMD and its comorbidities in KSA. Diabetes and stroke are key predictors, demonstrating the need for integrated chronic disease management strategies.},
}

@article {pmid42023256,
year = {2026},
author = {Sun, RS and Huo, SX and Zhang, TL and Ying, HJ and Wang, JH and Xu, LN and Luo, XL and Yang, Y and Hu, YD},
title = {Development of a predictive model for depressive symptoms in type 2 diabetes mellitus patients under community management: Based on visual function index.},
journal = {Ibrain},
volume = {12},
number = {1},
pages = {123-136},
pmid = {42023256},
issn = {2769-2795},
abstract = {Visual impairment has been recognized as a potential risk factor for depressive symptoms (DS) in diabetes patients, yet the role of visual function in predicting DS remains unexplored. This study aims to develop and validate a predictive model for DS risk in type 2 diabetes mellitus (T2DM) patients in community health settings, incorporating a visual function index (VF14). We conducted a cross-sectional study involving 542 T2DM patients from four community health centers in Guiyang. Univariate and multivariate logistic regressions identified significant predictors, while 10 machine learning algorithms were employed to construct the predictive model. Model performance was assessed using such metrics as receiver operating characteristic curves, accuracy, sensitivity, specificity, F1 score, Brier score, C-index, calibration curves, and decision curve analysis. A restricted cubic spline (RCS) analysis evaluated the score-dependent risk profiles between the VF14 and DS. Key predictors included body mass index (BMI), self-reported glycemic status, age-related macular degeneration, glycated hemoglobin (HbA1c), and VF14. Among the models, the gradient boosting machine exhibited the robust predictive performance, with an area under the curve of 0.73 and sensitivity of 0.72. The Shapley additive explanations analysis identified VF14, BMI, and HbA1c as the top risk factors. RCS analysis revealed a score-dependent risk profile between VF14 and DS risk. This study introduces a clinically interpretable tool for early DS risk stratification in T2DM patients, offering potential for improved risk assessment and timely intervention in community health settings.},
}

@article {pmid42024166,
year = {2026},
author = {Gregori, G and Sahoo, NK and Lall, SR and Sadeghi, E and Schulman, A and Hasan, N and Chhablani, J},
title = {High choroidal vascularity index zones favor the distribution of drusenoid pigment epithelial detachment in intermediate age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42024166},
issn = {1435-702X},
}

@article {pmid42025255,
year = {2026},
author = {Sagnard, M and Valero, B and D'aiello, A and Agard, E and El Chehab, H},
title = {Ocular risks related to light overexposure in maritime professionals in the Provence-Alpes-Côte d'Azur Region, France: The PHOTOPPA study.},
journal = {Journal francais d'ophtalmologie},
volume = {49},
number = {5},
pages = {104885},
doi = {10.1016/j.jfo.2026.104885},
pmid = {42025255},
issn = {1773-0597},
abstract = {PURPOSE: To assess the prevalence of light-induced toxic effects on the ocular and palpebral regions in maritime professionals chronically exposed to light radiation in the Provence-Alpes-Côte d'Azur region and to compare the results to a non-overexposed population. The study also investigates risk factors for and protective factors against ocular phototoxicity in exposed individuals.

DESIGN: Single-center, cross-sectional comparative analysis.

PARTICIPANTS: The study included 77 maritime professionals (overexposed group) and 70 non-overexposed individuals (control group). Participants were examined between July 2023 and June 2024 at the ophthalmology department of Sainte-Anne Military Hospital.

METHODS: Cross-sectional comparative analysis was performed between the two groups. Participants underwent a clinical examination, including ocular imaging, focused on ocular conditions such as conjunctival lesions, cataracts, and macular changes linked to light overexposure, and completed questionnaires on sun exposure.

RESULTS: The study found no connection between age-related macular degeneration (AMD) and solar overexposure but highlighted the significant role of light reflection from water in other ocular conditions. Four basal cell carcinomas were found in the exposed group, consistent with the pathogenesis of these skin cancers. A higher risk of conjunctival lesions (pinguecula and/or pterygium) and cortical cataracts was noted. Macular epithelial damage was linked to increased light exposure. Protective solar equipment reduced the risk of ocular damage in certain conditions.

CONCLUSIONS: The PHOTOPPA study is the first to compare ocular pathologies related to light overexposure in maritime professionals. It confirms the increased risk of ocular conditions, emphasizing the importance of comprehensive sun protection to reduce light-induced ocular damage and possibly prevent AMD development.},
}

@article {pmid42025869,
year = {2026},
author = {Abdouh, M and Sebag, W and Abdouh, N and Goyeneche, A and Burnier, MN},
title = {Differential protective effects of blue light (BL)-exposed retinal pigment epithelial cells by selective BL-filtering lenses.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111034},
doi = {10.1016/j.exer.2026.111034},
pmid = {42025869},
issn = {1096-0007},
abstract = {Blue light (BL) is harmful to eye posterior segment structures. It induces accelerated retina aging and the progression of retinal diseases. We reported that BL is cytotoxic to retinal pigment epithelial (RPE) cell through oxidative damage. Herein, we investigated the potential of selective BL-filtering intraocular lenses (BL-IOL) to mitigate these deleterious effects. Human RPE cells were exposed to BL in the absence or presence of a panel of BL-IOLs having different pigment compositions and BL-filtering potentials. Cells were analyzed for their oxidative status (levels of reactive oxygen species (ROS) and mitochondrial membrane potential (ΔΨM)), and growth (proliferation, metabolic activity and viability). Exposure of RPE cells to BL significantly increased the levels of cellular ROS and mitochondrial superoxide anion. While these effects did not affect cell proliferation, they triggered a collapse of the ΔΨM, a decrease in cell metabolic activity and an increase of cell death. Independent of the BL-IOL used in the BL beam, there was a drop in oxidative stress and ensuing protection of cells from the BL-mediated cytotoxic effects. Notably, BL-IOL with higher filtration potential of high-energy BL provided better photoprotection to exposed cells. This study highlights the need to selectively filter BL radiation wavelengths from light reaching the eye. It will help to define the best filtering devices to prevent RPE cell damage and eye posterior segment structure-related disease progression, such as during age-related macular degeneration.},
}

@article {pmid42026508,
year = {2026},
author = {Chi, SC and Hwang, DK and Chen, SJ and Weng, CC and Huang, YM and Chou, YB and Lin, TC},
title = {Short-term efficacy of aflibercept 8 mg in refractory neovascular age-related macular degeneration: a retrospective case series from Taiwan.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04848-z},
pmid = {42026508},
issn = {1471-2415},
support = {(CI-113-26)//Yen Tjing Ling Medical Foundation/ ; V114C-191//Taipei Veterans General Hospital/ ; },
}

@article {pmid42015048,
year = {2026},
author = {Ma, Q and Liu, X and Li, J and Bai, Y and Mu, W and Li, N and Yan, B and Wang, Z},
title = {AMD-UPerNet: a tool for retinal layer and fluid assessment in age-related macular degeneration.},
journal = {BMC medical imaging},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12880-026-02349-5},
pmid = {42015048},
issn = {1471-2342},
}

@article {pmid42017182,
year = {2026},
author = {Sivachandran, N and Ji, PX and Khan, H and Pickel, L and Mojumder, O and Aziz, AA and Khan, H and Sulahria, H and Gahn, GM and Khanani, AM},
title = {Visual and Anatomic Outcomes of Faricimab in Naïve Neovascular Age-Related Macular Degeneration with Subretinal Hemorrhage: A Multi-Centre Retrospective Analysis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {589703},
pmid = {42017182},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate functional and anatomical outcomes of faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD) presenting with subretinal hemorrhage (SRH).

SUBJECTS AND METHODS: A multicenter retrospective chart review was completed in retina practices in Canada and the United States from June 2022 to September 2025. Treatment-naïve nAMD patients with SRH receiving faricimab were evaluated. Standardized imaging protocols and treat-and-extend guidelines were employed. Primary outcome was visual acuity (VA) change; secondary outcomes included central subfield thickness (CST), pigment epithelial detachment (PED) height, and qualitative assessment of subretinal hyperreflective material (SHRM) and subretinal fibrosis. Outcomes were analyzed following three consecutive loading doses using Friedman statistics for repeated measures. Paired analysis was performed using Wilcoxon signed rank test. Detailed characterization of SRH included measurements of hemorrhage size in disc diameters (DD), location in terms of subfoveal versus extrafoveal, and duration from symptom onset to treatment initiation. Univariate regression analysis was performed to identify predictors of SRH resolution (effect ratio and 95% CI) and visual acuity improvement (odds ratio and 95% CI).

RESULTS: This study included 63 treatment-naïve patients with nAMD and SRH (mean age was 81.6 ± 8.2 years; 58.2% females; n = 28 from Canada and n = 35 from United States; mean total follow-up duration was 17.5 ± 6.0 months). Significant VA improvement was observed (Friedman statistic: 26.3, p < 0.00001), with 42.6% of patients gaining ≥3 lines of vision after loading doses. CST decreased substantially from 391.8 µm to 249.4 µm (p < 0.00001, z = -5.48) and mean PED height reduced from 309.6 µm to 110.7 µm (p < 0.00001, z = -3.51). SHRM and subretinal fibrosis were noted in 81.6% and 25.4% of cases, respectively, at baseline. Of this, 70% had resolution of SHRM and 50% had improvement in fibrosis, at last follow up visit. Univariate analysis of predictors of faricimab injection account to achieve SRH resolution in n = 33 patients identified three significant predictors: SHRM-presence at baseline (effect ratio = 0.531, 95% CI 0.399-0.707, p < 0.0001), combined intraretinal fluid (IRF) and subretinal fluid (SRF) (effect ratio = 1.43, 95% CI 1.09-1.87, p = 0.011), and non-Caucasian ethnicity (effect ratio = 1.45, 95% CI 1.03-2.04, p = 0.031). Analysis of predictors of VA improvement >3 lines did not reveal any clinically meaningful associations.

CONCLUSION: This study demonstrates faricimab's efficacy in nAMD with SRH, a challenging phenotype traditionally associated with poor visual prognosis. The dual-pathway inhibition of VEGF-A and Ang-2 achieved rapid hemorrhage clearance and meaningful vision gains, offering clinical hope for this high-risk population.},
}

@article {pmid42017838,
year = {2026},
author = {Cui, X and Yuan, J and Zhao, Q and Yu-Wai-Man, P and Zheng, T},
title = {Sleep Regularity and Age-Related Eye Diseases: Prospective Analyses with Retinal Imaging and Multimorbidity Assessment in the UK Biobank.},
journal = {Sleep},
volume = {},
number = {},
pages = {},
doi = {10.1093/sleep/zsag111},
pmid = {42017838},
issn = {1550-9109},
abstract = {STUDY OBJECTIVES: Sleep regularity, a key circadian dimension of sleep health, has been linked to cardiometabolic and neurodegenerative outcomes, yet its relevance to ocular ageing remains unclear. The retina is a metabolically active, circadian-regulated neural tissue, suggesting that irregular sleep may contribute to the development of age-related eye diseases.

METHODS: We studied 78,839 adults in the UK Biobank. Sleep regularity was quantified using the Sleep Regularity Index (SRI). Associations with age-related macular degeneration (AMD), cataract, glaucoma, retinal vein occlusion (RVO), and diabetic retinopathy (DR) were examined using Cox models, restricted cubic splines, subgroup analyses, and propensity-score matching. Retinal structural and vascular metrics were additionally evaluated. Nomogram models integrating SRI with clinical risk factors were developed.

RESULTS: Lower SRI was consistently associated with higher risks of AMD (HR=0.87), cataract (HR=0.95), and glaucoma (HR=0.89), with clear dose-response patterns; no robust associations were found for RVO or DR. Higher SRI correlated with greater macular, retinal ganglion cell (RGC), and retinal nerve fiber layer (RNFL) thicknesses, and with more favourable retinal vascular geometry. Incorporating SRI improved prediction performance for AMD, cataract, and glaucoma (AUC 0.72-0.74). SRI also declined markedly with increasing ocular multimorbidity.

CONCLUSIONS: Sleep regularity was consistently associated with major age-related eye diseases, ocular multimorbidity, and retinal structural and vascular characteristics. These findings highlight sleep regularity as a clinically relevant behavioural correlate of ocular ageing and a potential adjunctive marker for prevention-oriented risk stratification.},
}

@article {pmid42018151,
year = {2026},
author = {Nielsen, MA and Bjerager, J and Citirak, G and Subhi, Y and Holm, LM and Singh, A},
title = {Charles Bonnet syndrome in patients referred for cataract surgery.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42018151},
issn = {1435-702X},
abstract = {PURPOSE: To investigate the prevalence and clinical characteristics of Charles Bonnet Syndrome (CBS) in patients referred for bilateral cataract surgery.

METHODS: This prospective, cross-sectional clinical trial included 391 patients attending cataract assessment at a single-center tertiary cataract clinic. After clinical examination, participants were screened for presence of visual hallucinations (VHs). Participants experiencing complex VHs were further questioned regarding characteristics of their hallucinatory experiences to properly determine if they were attributable to CBS. CBS was defined as complex visual hallucinations with retained insight, no medical history or medication known to cause hallucinations and not limited to hypnagogic or hypnopompic states (hallucinations happening shortly before falling asleep and/or shortly after waking up).

RESULTS: Nineteen (4.9%) patients experienced complex VHs. Of these, 11 (2.8%) were diagnosed with CBS while 8 (2.1%) had complex hypnagogic and/or hypnopompic VHs. Multivariable logistic regression analysis identified lower best-corrected visual acuity (BCVA) in the better seeing eye as a significant predictor of CBS. When excluding participants with a BCVA>0.3, prevalence of complex VHs rose to 10.0%. Three of the patients with CBS (27.3%) had ocular comorbidities: two had exudative age-related macular degeneration (AMD), and one had drusenoid AMD. In the overall cohort, twenty-four patients (6.1%) reported prior knowledge of CBS.  CONCLUSION: CBS was observed in a clinically relevant minority of cataract patients requiring bilateral surgical intervention. Given the high prevalence of cataract among the elderly, this study highlights the importance of healthcare personnel being aware of CBS and other complex VHs and their potential consequences for cataract patients.},
}

@article {pmid42018574,
year = {2026},
author = {Vavvas, DG},
title = {Photobiomodulation in Dry Age-Related Macular Degeneration: Promising Signal, Familiar Questions.},
journal = {Retina (Philadelphia, Pa.)},
volume = {46},
number = {5},
pages = {765-767},
doi = {10.1097/IAE.0000000000004823},
pmid = {42018574},
issn = {1539-2864},
}

@article {pmid42019353,
year = {2026},
author = {Deng, Q and Kishimoto, K and Sugiyama, O and Miyake, M and Tamura, H},
title = {Automatic selection of optical coherence tomography images for prognostic prediction models in age-related macular degeneration.},
journal = {Computer methods and programs in biomedicine},
volume = {282},
number = {},
pages = {109384},
doi = {10.1016/j.cmpb.2026.109384},
pmid = {42019353},
issn = {1872-7565},
abstract = {BACKGROUND AND OBJECTIVE: Age-related macular degeneration (AMD) is a leading cause of blindness. Current standard treatments require frequent intravitreal injections and entail high costs, placing a heavy burden on patients and healthcare providers. These challenges often lead to treatment discontinuation or overtreatment, highlighting the need for personalized AMD management. Accurate early prediction of long-term treatment outcomes is critical for optimizing these strategies. However, most existing prognostic models rely heavily on manual image selection by ophthalmologists. This labor-intensive process, which requires carefully selecting suitable images from large volumes of electronic medical record (EMR) data, significantly hinders real-world implementation. This study proposes an automated deep learning framework to select appropriate images from extensive EMR-stored optical coherence tomography (OCT) reports, thereby reducing the reliance on manual curation.

METHODS: We developed a vision transformer (ViT)-based architecture to perform automated image selection. The model integrates features from the fundus infrared reflectance (IR) images and the corresponding OCT images presented in the clinical reports.

RESULTS: Compared to related works using a single OCT image input, the proposed method outperformed to the baseline. At training the pretrained ViT framework achieved an overall accuracy of 89% in identifying suitable images. Furthermore, using the images selected by our method improved the downstream prognostic prediction accuracy by an average of 3.1 percentage points. Confidence scores showed a statistically significant difference between the proposed method and the baseline (p = 0.026). The 95% confidence interval (CI) of the performance difference was [0.002, 0.066].

CONCLUSIONS: These results demonstrate the feasibility of an automated module capable of reliably identifying suitable images for AMD prognosis. By streamlining image selection workflows, this approach can enhance clinical efficiency, support the accurate estimation of long-term treatment effects, and facilitate treatment planning.},
}

@article {pmid42019593,
year = {2026},
author = {Goncalves, L and Hashimoto, Y and Barthelmes, D and Barry, R and Pollreisz, A and Wolff, B and Toole, LO and Ponsioen, TL and Morros, HB and Creuzot-Garcher, C and Gillies, M and Gabrielle, PH},
title = {Real-World Outcomes in Neovascular AMD with Visit Gaps under Anti-VEGF Therapy: Data from the FRB! Registry.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.04.007},
pmid = {42019593},
issn = {2468-6530},
abstract = {PURPOSE: To evaluate visual outcomes observed across visit gaps in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) therapy in routine clinical practice.

DESIGN: Retrospective data analysis from a prospectively designed observational outcomes registry: the Fight Retinal Blindness! (FRB!).

PARTICIPANTS: Treatment-naïve nAMD eyes receiving intravitreal anti-VEGF therapy (≥1 injection), monitored at least quarterly during the first treatment year, and experiencing a visit gap of ≥6 to 12 months, with subsequent follow-up over the next 9 months (≥3 visits).

METHODS: Visual outcomes were assessed using a segmented linear mixed-effect model. Cumulative incidence and risk factors for visit gaps were evaluated using Aalen-Johansen estimators and Cox regression models.

MAIN OUTCOME MEASURES: The main outcome was the mean estimated change in VA immediately after the visit gap. Secondary outcomes included the cumulative incidence and associated risk factors of visit gaps.

RESULTS: From 3694 eligible eyes for the survival analysis, we tracked 262 (7.1%) eligible eyes experiencing a visit gap for the visual outcome analysis. nAMD-treated eyes experiencing a 6-12 month visit gap had a significant drop in vision immediately after the visit gap, with a mean (95% confidence interval [CI]) estimated change in VA of -4.9 letters (-6.0 to -3.7; P < 0.001). Eyes with active choroidal neovascularization (CNV) lesions (difference -3.9 [-7.1 to -0.3] letters vs. inactive CNV) and without subfoveal macular atrophy (MA) (difference 3.4 [-0.3 to 7.0] letters vs. subfoveal MA) at the last visit before the gap experienced a greater decline in VA after the visit gap. A quarter of the eyes experienced a 6-12 month visit gap at 6.5 years. nAMD eyes with a longer time interval since last injection were more likely to experience a visit gap, while eyes with better VA and that had active CNV with subretinal fluid only at follow-up visits were less likely.

CONCLUSIONS: Visit gaps were common and associated with a significant visual decline across the visit gap in nAMD eyes treated with anti-VEGF therapy in routine clinical practice.},
}

@article {pmid42020899,
year = {2026},
author = {Kumar, S and Zhao, D and Wong, VHY and Bui, BV and Liu, GS},
title = {Evaluation of CRISPR/CasRx-Mediated VEGF mRNA Knockdown in Mouse Retina.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {3023},
number = {},
pages = {25-37},
pmid = {42020899},
issn = {1940-6029},
abstract = {Neovascular eye diseases (NEDs) are a group of diseases caused by the abnormal overgrowth of blood vessels in the eye. Normal vasculature is maintained through a dynamic balance of the vascular endothelial growth factor (VEGF). In diseases such as advanced diabetic retinopathy (DR) and neovascular age-related macular degeneration (AMD), an overexpression of VEGF leads to the formation of structurally weak and leaky blood vessels, resulting in vision impairment and, without intervention, legal blindness. In the clinic, NEDs are presently managed through anti-VEGF agents that specifically bind and neutralize VEGF signaling. While effective, this approach requires invasive intravitreal injections monthly and places a heavy burden on patients and healthcare providers. A flexible, long-lasting therapeutic that can reduce or eliminate frequent anti-VEGF treatment will significantly advance NED management.RNA editing with clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) is an emerging strategy to achieve reversible gene editing. The CRISPR-Cas13 system exclusively targets single-stranded RNA and allows gene silencing in a safe manner through RNA knockdown, as the genome is left intact. In addition, the compact CasRx enzyme (930aa) allows RNA silencing to be achieved through the delivery of a single adeno-associated virus (AAV), ideal for gene therapy applications. Herein, we outline methods to target VEGFA mRNA using CRISPR/CasRx in a mammalian cell line and humanized VEGFA transgenic mice.},
}

@article {pmid42020902,
year = {2026},
author = {Hall, J and Cheung, S and Shobhana, K and Cho, E and Lidgerwood, GE and Paull, D and Pébay, A},
title = {Quantification of Drusen-Like Deposits in Human Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Cells Using Confocal Microscopy.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {3023},
number = {},
pages = {59-80},
pmid = {42020902},
issn = {1940-6029},
abstract = {Accessing pathologically relevant models of human retinal degeneration is crucial for understanding, screening, and developing accurate treatment strategies that prevent or slow progression of blinding diseases. Human pluripotent stem cells (hPSCs) are a powerful tool to investigate retinal disease, as cells from selected individuals or specific genetic background can be differentiated into cell types of interest. hPSC-derived retinal pigment epithelium (RPE) cells can produce drusen-like deposits that accumulate between the RPE and the underlying Bruch's membrane. These key pathological markers of specific retinal disorders are detectable using simple microscopy techniques. However, quantification of these deposits often requires slow, low-throughput manual counting of images. This further lends itself to issues including sampling biases while ignoring critical data parameters such as deposit volume and precise localization. To overcome these issues, we developed two methods for quantifying the presence of drusen-like deposits in vitro, using hPSC-derived RPE cultures. Both methods accurately quantify drusen-like deposit numbers, and the mid-throughput pipeline allows for quantification of drusen-like deposit volume, as well as discerns their apical or basal localization on RPE cells. The platform's ability to track changes in drusen-like deposits supports screening experimentation and personalized medicine initiatives, including for gene therapy optimization.},
}

@article {pmid42020908,
year = {2026},
author = {Miller, AL and Bhatt, Y and Carvalho, LS},
title = {Intravitreal Injections in Mouse Models of Eye Disease.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {3023},
number = {},
pages = {167-176},
pmid = {42020908},
issn = {1940-6029},
abstract = {Intravitreal injections are a commonly used technique in the treatment of some vitreoretinal diseases. In clinical situations, intravitreal injections are often used to deliver drugs that treat diseases such as age-related macular degeneration, retinal vein occlusion, and uveitis. Many preclinical studies in animals such as mice utilize intravitreal injections to test neuroprotective treatments and gene therapies before clinical use can be indicated. Herein, we describe our method and favorable practices for intravitreal injection into the eye of both preweaned and adult mice.},
}

@article {pmid42008990,
year = {2026},
author = {Said, S and Knecht-Bösch, M and Knecht-Bosch, P},
title = {Switching to the Biosimilar Ranibizumab-nuna for the Intravitreal Treatment of Retinal Diseases - a Real-World Study.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {243},
number = {4},
pages = {434-439},
doi = {10.1055/a-2803-9757},
pmid = {42008990},
issn = {1439-3999},
mesh = {Humans ; *Ranibizumab/administration & dosage/adverse effects/therapeutic use ; Female ; Male ; Retrospective Studies ; Aged ; Middle Aged ; Intravitreal Injections ; Aged, 80 and over ; *Biosimilar Pharmaceuticals/administration & dosage/adverse effects/therapeutic use ; *Drug Substitution ; Tomography, Optical Coherence ; *Retinal Diseases/drug therapy ; Visual Acuity/drug effects ; Treatment Outcome ; Angiogenesis Inhibitors/administration & dosage ; },
abstract = {ABSTRACT: INTRODUCTION: Following the expiration of ranibizumab's (Lucentis) patent, the biosimilar ranibizumab-nuna (Byooviz) offers an alternative intravitreal medication with identical indications. However, real-world data on its efficacy remain limited. This study aimed to investigate the efficacy and safety of retinal disorders in patients who were switched from Lucentis to Byooviz.

ABSTRACT: METHODS: This retrospective, single-center study assessed adult patients previously treated with intravitreal Lucentis and switched to Byooviz. We evaluated structural and functional outcomes based on Snellen visual acuity (VA), fundoscopy, and optical coherence tomography (OCT) parameters, and treatment safety. Disease activity was classified as active or inactive, with neovascular activity defined as retinal pigment epithelial detachments, intra- or subretinal fluid, subretinal hyperreflective material, or macular hemorrhage on OCT or fundoscopy.

ABSTRACT: RESULTS: Between June 2021 and December 2024, we identified 31 patients, 21 (67.7%) of whom were female. Median (IQR, range) age was 82 (76.5 to 85.5, 49 to 91) years. The most common indication was neovascular age-related macular degeneration (61.3%), followed by macular edema (ME) due to retinal vein occlusion (22.6%), diabetic ME (9.7%), and secondary choroidal neovascularization (6.5%). Right and left eyes were nearly equally represented (48.4% vs. 51.6%). The median (IQR) injection numbers were 15 (10 to 40) for Lucentis and 8 (5 to 10.5) for Byooviz. After the switch, VA improved in 8 eyes (25.8%), was unchanged in 10 (32.3%), and worsened in 13 (41.9%). Disease activity decreased in 6 eyes (20%), increased in 3 (10%), and remained stable in 22 (70%). Treatment intervals shortened in 8 (25.8%) patients and extended in 14 (45.2%). No cases of endophthalmitis or other complications occurred.

ABSTRACT: DISCUSSION: Switching from Lucentis to Byooviz was generally well tolerated, with anatomical disease stability maintained in most patients. Certain decline in VA is also be observed in real-world outcomes for Lucentis and may reflect underlying disease progression rather than reduced efficacy of the biosimilar. Overall, Byooviz seems to be a viable alternative for patients previously treated with Lucentis.},
}

Humans
*Ranibizumab/administration & dosage/adverse effects/therapeutic use
Female
Male
Retrospective Studies
Aged
Middle Aged
Intravitreal Injections
Aged, 80 and over
*Biosimilar Pharmaceuticals/administration & dosage/adverse effects/therapeutic use
*Drug Substitution
Tomography, Optical Coherence
*Retinal Diseases/drug therapy
Visual Acuity/drug effects
Treatment Outcome
Angiogenesis Inhibitors/administration & dosage

@article {pmid42008992,
year = {2026},
author = {Gabathuler, F and Cozzi, M and Fasler, K and Maloca, PM and Blaser, F and Zweifel, S},
title = {Real-World Case Series of Intravitreal Pegcetacoplan for Geographic Atrophy Secondary to Age-related Macular Degeneration in Switzerland.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {243},
number = {4},
pages = {461-464},
doi = {10.1055/a-2825-0926},
pmid = {42008992},
issn = {1439-3999},
mesh = {Humans ; *Geographic Atrophy/drug therapy/etiology/diagnosis ; Male ; Female ; Switzerland ; Intravitreal Injections ; Aged ; Retrospective Studies ; *Macular Degeneration/complications/drug therapy ; Aged, 80 and over ; Treatment Outcome ; Visual Acuity/drug effects ; Tomography, Optical Coherence/methods ; },
abstract = {ABSTRACT: PURPOSE: To report early real-world experience with intravitreal pegcetacoplan for geographic atrophy secondary to age-related macular degeneration in Switzerland.

ABSTRACT: METHODS: This retrospective case series included patients with geographic atrophy secondary to age-related macular degeneration treated with intravitreal pegcetacoplan. Treatment exposure, best-corrected visual acuity, adverse events, and follow-up were assessed. Geographic atrophy was quantified on macula-centred OCT scans using the RetinAI Discovery platform, based on automated segmentation of total photoreceptor and RPE atrophy.

ABSTRACT: RESULTS: Seven eyes from six patients were included, receiving a total of 37 intravitreal pegcetacoplan injections. The median number of injections per eye was five (range 3 - 8), with a mean injection interval of 9.5 ± 2.4 weeks. Follow-up duration ranged from 4.4 to 14.0 months. Median best-corrected visual acuity declined by 7 ETDRS letters over the observation period. Mean geographic atrophy area increased from 7.6 mm[2] at baseline to 8.7 mm[2] at last follow-up. No severe adverse events were recorded.

ABSTRACT: CONCLUSIONS: In this real-world case series, intravitreal pegcetacoplan was well tolerated without severe adverse events during short-term follow-up, while visual acuity decline and continued geographic atrophy progression were observed.},
}

Humans
*Geographic Atrophy/drug therapy/etiology/diagnosis
Male
Female
Switzerland
Intravitreal Injections
Aged
Retrospective Studies
*Macular Degeneration/complications/drug therapy
Aged, 80 and over
Treatment Outcome
Visual Acuity/drug effects
Tomography, Optical Coherence/methods

@article {pmid42009153,
year = {2026},
author = {Ge, Z and Jia, Z and Liu, Y and Zhang, H},
title = {Injectable hyaluronic acid hydrogels for the treatment of ocular diseases: A review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {152112},
doi = {10.1016/j.ijbiomac.2026.152112},
pmid = {42009153},
issn = {1879-0003},
abstract = {Globally, an increasing number of individuals suffer from ocular diseases, including dry eye syndrome, corneal injuries, and age-related macular degeneration (AMD), ultimately leading to visual impairment or complete blindness. The complex anatomy and physiological barriers of the eye limit the efficacy of conventional therapies such as eye drops and intraocular injections, while also posing challenges including frequent dosing requirements and inflammatory risks. Injectable hyaluronic acid (HA) hydrogels present a promising strategy to address the limitations of current ocular therapies, owing to their excellent biocompatibility, tunable physicochemical properties (including optical transparency and mechanical modulus), and sustained drug release capabilities. Recent research continues to explore the potential of functionalized injectable HA hydrogels to advance ophthalmic treatment paradigms. This review summarizes recent advances in the chemical modification and crosslinking strategies of HA, as well as innovative design concepts for functionalized injectable HA hydrogels in treating ocular disorders such as corneal injuries and age-related macular degeneration (AMD). Injectable HA hydrogels show considerable promise for improving therapeutic outcomes, reducing treatment frequency and side effects, lowering healthcare costs, and enhancing patient compliance. This review aims to provide theoretical support for the future development of emerging HA hydrogel-based platforms for ocular care.},
}

@article {pmid42009803,
year = {2026},
author = {Zeng, Q and Hua, X and Liu, Y and Wang, S},
title = {Oxidative stress promotes the progression of age-related macular degeneration by up-regulating Spp1 to activate the JAK/STAT signaling pathway.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-48556-6},
pmid = {42009803},
issn = {2045-2322},
}

@article {pmid42011167,
year = {2026},
author = {Ching, K and Meng, J and Wang, L and Cheng, K and He, W and Zhang, K and Lu, Y and Zhu, X},
title = {Swept-source OCTA assessment of iris vasculature as a biomarker for myopic macular degeneration severity.},
journal = {Advances in ophthalmology practice and research},
volume = {6},
number = {2},
pages = {139-145},
pmid = {42011167},
issn = {2667-3762},
abstract = {BACKGROUND: To investigate the vessel area density (VAD) and morphological features of the iris in patients at different stages of myopic macular degeneration (MMD) using swept-source optical coherence tomography angiography (SS-OCTA).

METHODS: In this retrospective case-control study, 106 eyes of 106 high myopia patients (axial length (AL) ≥26 mm) were included and classified into different MMD categories according to the International META-PM Classification. The VAD of iris, iris volume (IV), area of anterior iris surface (IS), area of posterior IS, and average iris thickness (IT) were evaluated using SS-OCTA. Associations among iris vasculature, iris morphology, and MMD categories were investigated.

RESULTS: Full-range, inner-region, and intermediate-region VAD of the iris decreased significantly with increasing MMD severity (all P-trend <0.001), whereas outer-region VAD did not show a significant linear trend. The area of IS was larger in eyes with MMD 2 and MMD 4 compared to the other two groups (all P <0.05). The full-range and outer-region VAD of iris was negatively correlated with AL, while the inner-region VAD of iris was positively correlated with the area of anterior and posterior IS, especially in eyes with MMD 2 (all P <0.05). Multivariate linear regression revealed that greater full-range, inner-region and intermediate-region VAD were all significantly associated with milder MMD, whereas greater outer-region VAD was significantly associated with shorter AL.

CONCLUSIONS: Iris blood flow, quantified by VAD, decreased with increasing MMD severity. Iris VAD may represent a promising candidate biomarker for non-invasive monitoring of MMD severity. Additionally, the association between VAD and AL or iris morphology varied across MMD categories.},
}

@article {pmid42011205,
year = {2026},
author = {Chen, ZJ and Yu, J and Ng, DSC and Ho, M and Zhu, X and Brelen, ME and Young, AL and Yam, JC and Tham, CC and Pang, CP and Chen, LJ},
title = {Associations of TNFRSF10A with Central Serous Chorioretinopathy, Polypoidal Choroidal Vasculopathy, and Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {5},
pages = {101161},
pmid = {42011205},
issn = {2666-9145},
abstract = {PURPOSE: To investigate the role of tumour necrosis factor receptor superfamily member 10A (TNFRSF10A) in chronic central serous chorioretinopathy (cCSCR), polypoidal choroidal vasculopathy (PCV), and neovascular age-related macular degeneration (nAMD).

DESIGN: Case-control genetic association study.

PARTICIPANTS: A total of 1478 Chinese participants were recruited, including 217 patients with cCSCR (174 without and 43 with macular neovascularization [MNV]), 288 patients with PCV, 341 patients with nAMD, and 632 healthy controls.

METHODS: Thirteen single-nucleotide polymorphisms (SNPs) in TNFRSF10A that covered both the promoter and coding regions were genotyped, including 12 haplotype-tagging SNPs and a manually selected reference SNP, rs13278062. Two variants showing significant deviation from Hardy-Weinberg equilibrium were excluded, leaving 11 SNPs for the final analysis. Logistic regression, adjusted for age and sex, was applied to assess both allelic and haplotype associations. Conditional analyses were conducted to evaluate independent effects. Single-nucleotide polymorphisms were annotated based on TNFRSF10A domains defined by UniProtKB.

MAIN OUTCOME MEASURES: Associations between individual SNPs and haplotypes in the TNFRSF10A with nAMD, PCV, and cCSCR (with or without MNV), respectively.

RESULTS: For cCSCR without MNV, 4 tagging SNPs showed significant associations: rs59693001 (odds ratio [OR] = 1.65, 95% confidence interval [CI]: 1.12 - 2.33; P = 0.0043), rs3808530 (OR = 1.91, 95% CI: 1.22 - 2.83; P = 0.0013), rs2235126 (OR = 1.74, 95% CI: 1.22 - 2.41; P = 7.50 × 10[-4]), and rs7814465 (OR = 1.66, 95% CI: 1.22 - 2.28; P = 0.0016). The reference SNP, rs13278062, also showed a significant association (OR = 1.81, 95% CI: 1.31 - 2.51; P = 3.64 × 10[-4]). In addition, 4 haplotypes within 2 blocks from a continuous region also showed significant associations. For PCV, only rs36005462 in an independent domain showed a marginally significant association (OR = 0.58; P = 0.0050). No significant association was identified for nAMD or cCSCR with MNV.

CONCLUSIONS: This study identified multiple TNFRSF10A variants associated with cCSCR without MNV, while a distinct protective SNP was linked to PCV. These findings provide preliminary evidence for varying TNFRSF10A association patterns across the pachychoroid disease spectrum.

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

@article {pmid42011963,
year = {2026},
author = {Posnic, A and Yagoub, S and Lebastard, C and Vaast, M and Poinas, A and Pabic, EL and Bellamy, JP and Delhay, C and Faure, S and Rouic, JL and Henry, A and Lebreton, O and Masse, H and Susini, F and Guillaumie, T and Fournier, I and Mainguy, A and Lez, ML and Khanna, RK and Mortemousque, G and George, A and Pipelart, V and Bernard, Y and Grimbert, P and Mazhar, D and Benzerroug, M and Briend, B and Clement, M and Jammes-Veaux, HP and Posnic, MP and Bonissent, A and Guyot, C and Rousseau, N and Dam, BTV and Bellot, L and Ferron, R and Meur, GL and Mouriaux, F and Weber, M and Maucourant, Y and Ducloyer, JB},
title = {Predictive factors for injection interval extension after switching to faricimab in neovascular AMD: The FAR WEST multicentre study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70134},
pmid = {42011963},
issn = {1755-3768},
support = {//Centre Hospitalier Universitaire de Nantes/ ; },
abstract = {PURPOSE: To assess whether switching to faricimab allowed extending injection intervals after 12 months (M12) in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.

DESIGN: FAR WEST was a multicentre, observational, retrospective cohort study.

PARTICIPANTS: Patients with nAMD treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections for at least 1 year before switching to faricimab.

METHODS: The reason for switching (clinician's intent to extend the interval in the absence or presence of a recurrence or refractory status), and the switch strategy (whether an induction phase comprising 2, 3 or 4 injections was performed using the same or a shorter interval, or whether the interval was immediately extended from the second injection without induction) were left to the physician's discretion.

MAIN OUTCOME MEASURES: The following data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M12 follow-up visit: recurrence-free interval, last injection interval, best-corrected visual acuity (BCVA), central macular thickness (CMT), exudation status and intraocular inflammation events.

RESULTS: A total of 845 eyes of 718 patients were included in 23 centres. The recurrence-free injection interval increased significantly from 5.7 weeks at M0 to 8.6 weeks at M12 (difference: +2.9 weeks, p < 0.001). The proportion of exudative patients decreased from 571 (68%) to 337 (42%) (- 41%, p < 0.001). BCVA decreased from 0.33 (20/40) to 0.35 logMAR (20/40) (p = 0.0038). Among 238 refractory cases at M0, 84 (35%) achieved a dry macula at M12. In multivariable analysis, absence of an induction phase was associated with greater injection interval gain. (p < 0.001). There were no differences according to time since the first injection, type of neovascularization. The number of injections per year decreased from 8.7 at M0 to 6.1 at M12 (-2.6, p < 0.001), and the number of consultations decreased from 6.1 at M0 to 5.2 at M12 (-0.9, p < 0.001). The intraocular inflammation rate was 1.6% (n = 14).

CONCLUSION: Switching to faricimab allowed significantly extending the recurrence-free injection interval, decreasing the proportion of exudative patients and reducing the therapeutic burden in nAMD patients. Further studies are needed to determine the most appropriate switching modalities and which patients actually require an induction phase.},
}

@article {pmid42012273,
year = {2026},
author = {Shi, J and Xu, H and Zhao, H and Zhao, J and Chen, L and Xu, P and Jia, D and Jiang, C},
title = {Safety and Efficacy of cceAAV-aflibercept-Fc-YTE (F-CRG-B191): A Gene Therapy for Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {47},
doi = {10.1167/iovs.67.4.47},
pmid = {42012273},
issn = {1552-5783},
mesh = {Animals ; *Genetic Therapy/methods ; *Recombinant Fusion Proteins/therapeutic use/genetics ; *Receptors, Vascular Endothelial Growth Factor/therapeutic use/genetics ; Mice ; Disease Models, Animal ; Humans ; Dependovirus/genetics ; *Choroidal Neovascularization/therapy ; Genetic Vectors ; Female ; Male ; *Wet Macular Degeneration/therapy ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Intravitreal Injections ; Treatment Outcome ; Visual Acuity ; Mice, Inbred C57BL ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: To evaluate the safety and efficacy of a novel gene therapy vector, covalently closed-end double-stranded adeno-associated virus-aflibercept-Fc-YTE (cceAAV-aflibercept-Fc-YTE; clinical trial name F-CRG-B191), designed for sustained anti-vascular endothelial growth factor (VEGF) expression in the treatment of neovascular age-related macular degeneration (nAMD).

METHODS: We developed cceAAV-aflibercept-Fc-YTE. The therapeutic efficacy of cceAAV-aflibercept-Fc-YTE was evaluated in both mice and non-human primate (NHP) models with laser-induced choroidal neovascularization (CNV). The incidence of grade IV CNV lesions was quantified. A first-in-human administration of F-CRG-B191 was conducted to assess anatomical and functional outcomes, as well as safety. Immune responses and retinal toxicity were monitored in NHPs and the patient post-injection.

RESULTS: Compared to conventional AAV vectors expressing aflibercept, cceAAV-aflibercept-Fc-YTE significantly reduced the incidence of grade IV CNV lesions in both mice and NHP models. In the human subject, F-CRG-B191 administration led to a sustained reduction in CNV area and improvement in visual acuity. No significant immune response or retinal toxicity was observed in either preclinical models or the treated patient.

CONCLUSIONS: cceAAV-aflibercept-Fc-YTE (F-CRG-B191) is a promising gene therapy candidate for nAMD, demonstrating potent anti-VEGF efficacy, durable therapeutic effects, and favorable safety profiles in both preclinical and early clinical settings.},
}

Animals
*Genetic Therapy/methods
*Recombinant Fusion Proteins/therapeutic use/genetics
*Receptors, Vascular Endothelial Growth Factor/therapeutic use/genetics
Mice
Disease Models, Animal
Humans
Dependovirus/genetics
*Choroidal Neovascularization/therapy
Genetic Vectors
Female
Male
*Wet Macular Degeneration/therapy
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Intravitreal Injections
Treatment Outcome
Visual Acuity
Mice, Inbred C57BL
Tomography, Optical Coherence

@article {pmid42012371,
year = {2026},
author = {Cha, E and Youn, J and Yun, C and Kim, SW and Choi, M},
title = {Impact of Phacoemulsification on Neovascular Age-Related Macular Degeneration Activity: Predictive Role of Choroidal Vascularity and MNV Subtypes.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004864},
pmid = {42012371},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the impact of cataract surgery on disease activity in neovascular age-related macular degeneration (nAMD) and determine whether choroidal biomarkers and macular neovascularization (MNV) subtypes predict increased postoperative treatment requirements.

METHODS: This retrospective study included 84 eyes from 84 patients with nAMD who underwent phacoemulsification while receiving intravitreal anti-VEGF therapy. Increased treatment need was defined as a shortened injection interval or occurrence of submacular hemorrhage. Pre-and postoperative choroidal vascularity index (CVI), subfoveal choroidal thickness (SFCT), and central subfield thickness (CST) were analyzed using EDI-OCT within 1 month before and after surgery. MNV subtypes were classified as type 1, type 2, retinal angiomatous proliferation (RAP), and polypoidal choroidal vasculopathy (PCV).

RESULTS: Best-corrected visual acuity remained stable after cataract surgery (from 0.39 ± 0.27 [20/50] to 0.38 ± 0.28 logMAR [20/50]; p = 0.907), with no significant differences among MNV subtypes. Increased treatment need occurred in 45.2% of eyes. Both CVI and SFCT increased significantly postoperatively (p < 0.001). Eyes with increased treatment need showed significantly higher preoperative and postoperative CVI (p = 0.003 and p = 0.032, respectively). The PCV subtype demonstrated the highest rates of increased treatment need and the shortest injection intervals. Higher preoperative CVI independently predicted increased postoperative treatment need (OR = 1.13; p = 0.019).

CONCLUSIONS: Cataract surgery may affect disease activity in a subset of patients with nAMD, particularly those with PCV and increased CVI. Preoperative choroidal characteristics such as CVI and SFCT may provide valuable insights for risk stratification and postoperative management.},
}

@article {pmid42012698,
year = {2026},
author = {Herold, TR and Finger, RP and Bauer-Steinhusen, U and Lommatzsch, A and Ziemssen, F},
title = {Opportunities to Improve Management of Neovascular Age-related Macular Degeneration: Communication at Diagnosis and Beyond : Insights from the German nAMD Barometer Survey.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42012698},
issn = {1435-702X},
}

@article {pmid42013734,
year = {2026},
author = {Casablanca-Piñera, A and Alforja-Castiella, MS and Casaroli-Marano, RP},
title = {Changes on imaging after 10years of follow-up for concurrent melanocytoma and congenital hypertrophy of the retinal pigment epithelium in a patient treated with anti-VEGF intravitreal therapy for neovascular age-related macular degeneration.},
journal = {Journal francais d'ophtalmologie},
volume = {49},
number = {6},
pages = {104876},
doi = {10.1016/j.jfo.2026.104876},
pmid = {42013734},
issn = {1773-0597},
}

@article {pmid42014412,
year = {2026},
author = {Raul, P and Lee, T and Barry, R and Sabeti, F and van Boxtel, JJA},
title = {Visual noise in augmented reality improves vision in age-related macular degeneration.},
journal = {npj aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41514-026-00389-3},
pmid = {42014412},
issn = {2731-6068},
support = {DP220100406//Australian Research Council/ ; },
abstract = {Exudative age-related macular degeneration (eAMD) is a degenerative eye disease of the central retina that results in central vision loss, significantly affecting the daily functioning and quality of life of affected individuals. Although first-line treatments are quite effective in improving vision in eAMD, they are invasive and not suitable or efficacious for everyone. The non-invasive methods to enhance visual acuity (VA) in eAMD, are often limited in scope and burdensome for patients. Stochastic resonance (SR), a phenomenon in which optimal noise improves sensory perception, offers a promising non-invasive strategy with broad clinical potential. In this study, we tested whether visual noise delivered via an augmented reality (AR) headset enhanced binocular VA in binocular eAMD (N = 12) and in healthy individuals (N = 17) via the SR effect. Using a standard clinical letter chart, we observed an immediate improvement in vision, without the need for any training. Improvements were 2.5 letters and 2 letters at optimal noise levels for eAMD and healthy individuals, respectively. These findings demonstrate the potential of noise-based AR as a practical, wearable visual aid for individuals with eAMD or other visual disorders, offering enhancements that may complement or extend the benefits of current first-line treatments.},
}

@article {pmid42002030,
year = {2026},
author = {Fernández-Vigo, JI and Gallego-Pinazo, R and Montero Hernández, J and Arias-Barquet, L and Arévalo, FJ and García-Layana, A},
title = {Photodynamic therapy in neovascular age-related macular degeneration: Past or present in the era of second-generation anti-VEGF agents?.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {},
number = {},
pages = {502558},
doi = {10.1016/j.oftale.2026.502558},
pmid = {42002030},
issn = {2173-5794},
}

@article {pmid42002032,
year = {2026},
author = {Benedictus, B and Tsania, S and Ronik, HK and Dwinastiti, YA and Priscilla, B and Nova, E},
title = {Associations of Dose Adjustment with Efficacy and Safety of Faricimab for Age-related Macular Degeneration Disorders: A Systematic Review and Meta-analysis.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {},
number = {},
pages = {502562},
doi = {10.1016/j.oftale.2026.502562},
pmid = {42002032},
issn = {2173-5794},
abstract = {This paper reviews the efficacy and safety of various dosing regimens and treatment cycles of intravitreal faricimab as therapy for Age-related macular degeneration (ARMD). The included studies were randomized controlled trials (RCTs) or post-hoc analyses of RCTs involving a population of ARMD or macular related disorder patients receiving faricimab therapy. Study outcomes were assessed by best-corrected visual acuity (BCVA) or central macular subfield thickness (CST). Data extracted from the journals included characteristics of the patient population, subgroup population, treatment used, therapeutic dose, treatment cycle, BCVA, CVA, number of populations with severe adverse events, and severe ocular adverse events. Study heterogeneity was assessed using the I[2] statistic, with values ≤40% considered homogeneous. A random effects model was applied when effect estimates crossed the line of no effect. Effect sizes were reported as mean differences with 95% confidence intervals. We included eight studies with a total of 8458 study populations. There are several doses that can be given (1.5 mg and 6 mg) and several cycles of administration (every 4, 8, 12, 16 weeks and personalized treatment interval). Faricimab 6 mg every sixteen weeks has shown a better effect than aflibercept and ranibizumab. These findings suggest that faricimab 6 mg administered every sixteen weeks demonstrated superior outcomes in improving best-corrected visual acuity (BCVA) and greater reductions in central subfield thickness (CST) compared to aflibercept 2 mg every eight weeks. However, a more frequent regimens were associated with significantly higher severe adverse events, especially ocular severe adverse events.},
}

@article {pmid42003716,
year = {2026},
author = {Airody, A and Hanson, RLW and Bunola-Hadfield, I and Sivaprasad, S and Morland, AB and Chakravarthy, U and Gale, RP and , },
title = {The long-term impact of neovascular age-related macular degeneration undergoing routine treatment in first and second eyes on vision-related quality-of-life: FASBAT Report 3.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70150},
pmid = {42003716},
issn = {1755-3768},
support = {OAP030A2401T//Novartis Pharmaceuticals Corporation/ ; },
abstract = {PURPOSE: The study evaluated the long-term effect on vision-related quality-of-life (VRQoL) of routinely treated neovascular age-related macular degeneration (nAMD) in first and second eyes.

METHODS: The FASBAT (Observing Fibrosis, macular Atrophy and Subretinal highly reflective material Before and After Treatment with anti-VEGF treatment) study followed individuals with new unilateral nAMD (first eye) undergoing routine treatment for up to 4.5 years. Visual acuity (VA) was measured as part of routine care and VRQoL was assessed using the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25).

RESULTS: Of the 424 participants, 307 had only the first eye affected by nAMD (mean age = 76.5, SD = 8.4 years). The mean VA was 58.1 (SD = 15.5) and 79.4 (SD = 5.6) letters at baseline, and 58.4 (SD = 20.9)/78.5 (SD = 7.8) letters at 36-months in the affected and unaffected eyes, respectively. The mean composite NEI-VFQ-25 score was 87.1 (SD = 11.9) at baseline and 85.2 (SD = 13.5) at 36-months. One hundred and seventeen participants (mean age = 77.6, SD = 7.3 years) developed second eye nAMD, with a mean of 18.9 (SD = 10.2) months following the first eye. Mean VA in first and second eye was 56.3 (SD = 19.3)/74.1 (SD = 9.9) letters at the time of second eye development, and 51.1 (SD = 22.5)/73.6 (SD = 8.9) letters after 24-months. Mean composite NEI-VFQ-25 score was 81.4 (SD = 14.6) and 79.1 (SD = 17.2) at these time points.

CONCLUSIONS: Long-term VRQoL remains stable in unilateral treated nAMD. However, a clinically meaningful reduction in VRQoL occurs following development and treatment in the second eye which does not recover. It is important to offer appropriate support when the first and then second eye develop nAMD.},
}

@article {pmid42005206,
year = {2026},
author = {Faustine, G and Bastion, MC},
title = {A Case Series of Familial Macular Drusen: Clinical, Imaging, and Diagnostic Considerations in the Spectrum Between Age-Related Macular Degeneration (AMD) and Other Macular Disorders.},
journal = {Cureus},
volume = {18},
number = {3},
pages = {e105478},
pmid = {42005206},
issn = {2168-8184},
abstract = {Familial clustering of macular drusen in younger adults can mimic age-related macular degeneration (AMD) but may reflect an underlying inherited macular disorder. We describe a 72-year-old Chinese woman with high myopia and advanced neovascular AMD in one eye, who presented with progressive visual decline. Despite anti-vascular endothelial growth factor therapy, vision remained poor. Concerned about familial risk, her three adult children were examined. All three adult children (aged 46, 38, and 36 years) were asymptomatic despite drusen being detected on examination. This multigenerational clustering of drusen at relatively young ages raises suspicion for a possible hereditary macular disorder. This case highlights the need for family screening and genetic evaluation in atypical AMD presentations.},
}

@article {pmid42005909,
year = {2026},
author = {Lim, JI and Ambresin, A and Avery, RL and Chaikitmongkol, V and Eter, N and Gomi, F and Khanani, AM and London, NJS and Harrell, E and Margaron, P and Patel, S and Souverain, A and Yang, M and Lai, TYY},
title = {Reduction in Pigment Epithelial Detachment Thickness with Faricimab versus Aflibercept 2 mg during Head-to-Head Dosing in TENAYA/LUCERNE.},
journal = {Ophthalmology science},
volume = {6},
number = {5},
pages = {101148},
pmid = {42005909},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the effects of dual angiopoietin-2 (Ang-2)/VEGF-A pathway inhibition with faricimab versus VEGF pathway inhibition with aflibercept 2 mg on pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD).

DESIGN: TENAYA/LUCERNE (NCT03823287/NCT03823300) post hoc analysis.

PARTICIPANTS: Patients with treatment-naïve nAMD.

METHODS: Patients were randomized 1:1 to faricimab 6 mg up to every 16 weeks (n = 665) after 4 initial every-4-week (Q4W) doses or aflibercept 2 mg every 8 weeks (n = 664) after 3 Q4W doses. Pigment epithelial detachment was defined as retinal pigment epithelium (RPE) elevation width ≥350 μm and graded as predominantly/purely serous (serous PED) or predominantly/only fibrovascular (fibrovascular PED). Large PED definition: thickness ≥125 μm.

MAIN OUTCOME MEASURES: Pigment epithelial detachment thickness change from baseline during initial 12-week head-to-head dosing, proportion of patients with serous PED at the end of head-to-head dosing, and time to first reduction of maximum PED thickness by 50%.

RESULTS: Baseline PED characteristics were similar between arms. At week 12, the adjusted mean decrease from baseline in maximum PED thickness was greater with faricimab than aflibercept 2 mg in eyes with large (-119.1 [n = 500] vs. -101.4 μm [n = 496]; nominal P = 0.0028), serous (-136.1 [n = 128] vs. -108.2 μm [n = 114]; nominal P = 0.0147), and any type (-87.9 [n = 644] vs. -74.5 μm [n = 638]; nominal P = 0.0067) PED at baseline. The proportion of eyes with serous PED at baseline remaining serous at week 12 was lower with faricimab than aflibercept 2 mg (4.7% vs. 13.4%; nominal P = 0.0258). In eyes with large PED at baseline, the cumulative incidence of PEDs achieving time to first reduction of maximum PED thickness by 50% at week 12 was 35.3% with faricimab versus 25.7% with aflibercept 2 mg. The corresponding incidence in eyes with serous PED at baseline was 61.1% with faricimab versus 51.8% with aflibercept 2 mg. The incidence of RPE tears was low (faricimab, 2.9%; aflibercept 2 mg, 1.5%).

CONCLUSIONS: In TENAYA/LUCERNE, dual Ang-2/VEGF-A inhibition with faricimab elicited greater improvements in PED outcomes versus aflibercept 2 mg during head-to-head dosing. These findings are consistent with the greater drying of retinal fluid with faricimab during head-to-head dosing, which may allow for rapid treatment interval extension.

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

@article {pmid42005954,
year = {2026},
author = {Seddon, JM and De, D},
title = {The Macular Degeneration Preventive Diet and Lifestyle for Providers and Patients: From Evidence to Action.},
journal = {American journal of lifestyle medicine},
volume = {},
number = {},
pages = {15598276261438371},
pmid = {42005954},
issn = {1559-8284},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among older adults, with both genetic and modifiable risk factors contributing to disease progression. Robust prospective evidence demonstrates that dietary patterns rich in lutein, zeaxanthin, and omega-3 fatty acids-particularly through green leafy vegetables, fatty fish, and Mediterranean diet adherence-reduce AMD progression risk by 20-56% across disease stages. Lifestyle factors including smoking cessation, weight management, and regular physical activity also confer protective benefits. Despite ample evidence, counseling about the benefits of these dietary and lifestyle behaviors remains underutilized in ophthalmic practice, largely due to inadequate medical education in preventive medicine and perceived barriers to implementation of such recommendations. This perspective examines the current evidence, highlights the gap between scientific evidence and clinical implementation, and proposes a framework for systematic reform. Recommendations include embedding nutrition education into medical school and residency training, establishing ocular nutrition as a continuing education requirement, and equipping clinicians with tools for incorporating these guidelines into routine AMD clinical care. Aligning ophthalmic practice with the recommended nutritional guidelines and other behavioral changes through the Macular Degeneration Preventive Diet and Lifestyle, represents a timely opportunity to translate evidence into interventions that preserve vision.},
}

@article {pmid42007660,
year = {2026},
author = {Le, VH and El-Mulki, OS and Zhang, Y and Pan, H and Kumar, S and Shen, M and Beqiri, S and Badla, O and Berni, A and Kastner, J and Gregori, G and Rosenfeld, PJ and Wang, RK},
title = {Hyporeflective Core Drusen Cause an Artifactual Bending of Bruch's Membrane on OCT Images: Optical Mechanism and Proposed Quantitative Metrics.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {43},
doi = {10.1167/iovs.67.4.43},
pmid = {42007660},
issn = {1552-5783},
abstract = {PURPOSE: To investigate the optical mechanism and impact of the artifactual bending of Bruch's membrane (BM) beneath hyporeflective core drusen (hypoRCD) on optical coherence tomography (OCT).

METHODS: This observational and experimental laboratory study analyzed volumetric OCT scans with hypoRCD from an age-related macular degeneration (AMD) cohort. The optical mechanism underlying BM bending was examined using tissue phantoms with different oil droplets to model different refractive indices (RIs) of hyporeflective cores (hypoRCs). Three metrics were proposed to quantify hypoRCD: (1) hypocore bending index (CoreBI), (2) drusen bending index (DruBI), and (3) maximum bending index (Bmax). The impact of BM bending on choriocapillaris flow deficit (CCFD) analysis was assessed by comparing CCFD measurements before and after correcting BM segmentation under hypoRCD.

RESULTS: BM bending was consistently observed beneath the core region of hypoRCD in both structural OCT and optical attenuation coefficient (OAC) B-scans. Phantom experiments demonstrated that the bending was associated with differences in the RIs of the hypoRCs. The degree of bending, quantified by the CoreBI, increased with the RI of the core material (P < 0.001). The CCFD percentage beneath hypoRCD was significantly reduced by 25.9% ± 7.7% (P = 0.005) after correcting the BM segmentation. Morphological changes associated with the bending could be quantified using the three proposed metrics.

CONCLUSIONS: BM bending induced by hypoRCD is an artifactual OCT feature that reflects the optical properties of the hypoRCs. This morphological characteristic may improve our understanding of hypoRCD, raise cautions in quantitation of CCFDs under hypoRCD, and provide additional insights into their role in AMD.},
}

@article {pmid41814412,
year = {2026},
author = {Yin, W and Xu, M and Niu, Z and Gao, Y and Su, N and Song, Y and Liu, Q},
title = {Targeting CDH13 as a therapeutic strategy to mitigate pathological ocular angiogenesis.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41814412},
issn = {1479-5876},
support = {82471096//National Natural Science Foundation of China/ ; 82271100//National Natural Science Foundation of China/ ; },
abstract = {BACKGROUND: Anti-angiogenic therapies, which suppress pathological vessel growth in neovascular diseases such as diabetic retinopathy and neovascular age-related macular degeneration (nAMD), have transformed the clinical landscape. However, a critical unmet challenge is to shift the therapeutic paradigm from broad inhibition towards achieving vascular normalization, as non-selective angiogenic blockade can result in detrimental off-target effects. Consequently, the identification of novel molecular targets is imperative for developing more precise and effective treatment strategies.

METHODS: We evaluated CDH13 expression in fibrovascular membranes (FVMs) and nAMD derived from human using bioinformatics analysis and confirmed its presence in mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) via western blot, RT-PCR, and immunostaining. We then investigated CDH13 function through in vitro transwell, wound healing, and EdU assays following its knockdown, and extended our analysis in vivo using isolectin B4 staining, fundus fluorescein angiography, and immunofluorescent staining in mice subjected to CDH13 knockdown or treated with the oral inhibitor GW3965. Finally, we employed dual-luciferase reporter assays, RT-PCR, and western blot to elucidate the underlying molecular mechanisms.

RESULTS: We observed substantial CDH13 expression in endothelial cells of human nAMD fibrovascular membranes and mouse models of OIR and CNV. CDH13 knockdown inhibited pathological vessel growth, promoted vascular normalization, and induced a pro-regenerative environment. Mechanistically, hypoxia inhibits NR2F2, thereby de-repressing CDH13 transcription and activating the NF-κB pathway to drive vascular dysfunction. Additionally, oral GW3965 treatment reduced LDL deposition and alleviated pathological neovascularization through LXR activation, countering CDH13-mediated effects.

CONCLUSION: Together, these findings establish CDH13 as a promising therapeutic target for driving vascular normalization in neovascular retinal diseases.

GRAPHICAL ABSTRACT: [Image: see text]

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12967-026-07972-y.},
}

@article {pmid41999267,
year = {2026},
author = {Delcourt, C and Hucteau, E and Gattoussi, S and Pérès, K and Delyfer, MN and Helmer, C and Korobelnik, JF},
title = {Association of treated neovascular AMD with disability and mood disorders: A longitudinal nationwide study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70130},
pmid = {41999267},
issn = {1755-3768},
support = {//Bayer Healthcare (Lille, France)/ ; },
abstract = {PURPOSE: To describe the associations of treated neovascular AMD with the risk of disability, falls, fractures and mood disorders in a large sample representative of the French population.

METHODS: Analyses were based on 77 582 individuals belonging to the 'Echantillon Généraliste des Bénéficiaires', a 1/97 random sample of the French population, aged 65 years or more on 1 April 2009 and followed until 31 December 2019. Treated neovascular AMD (nAMD) was identified through the reimbursement of anti-VEGF drugs, intravitreal injections and after exclusion of other pathologies requiring the use of intravitreal anti-VEGFs. Activities of daily living (ADL) disability was identified using a previously developed algorithm, while falls, fractures, head trauma and mood disorders were identified using relevant ICD codes and medications. Associations of nAMD with outcomes were assessed using Cox models with nAMD as a time-dependent variable and adjustment for confounders.

RESULTS: During the study period, 1662 cases of incident nAMD were identified. After adjustment for age, sex, Charlson comorbidity index and number of drugs, nAMD was significantly associated with the occurrence of ADL disability (Hazard ratio (HR): 1.19, 95% confidence interval (CI): 1.08-1.30; p = 0.0002) and of mood disorders (HR: 1.19, 95%CI: 1.07-1.32; p = 0.002). Associations with falls, fractures and head trauma were not statistically significant.

CONCLUSION: Treated neovascular AMD remains associated with a 19% increased risk of disability and mood disorders, while no association was detected with falls, fractures and head trauma. These results are consistent with a major improvement in functional outcomes, with respect to the pre-anti-VEGF era.},
}

@article {pmid41999355,
year = {2026},
author = {Thomsen, AK and Villarruel Hinnerskov, JM and Maung, M and Mutschler, A and Sadda, S and Sørensen, TL},
title = {Junctional sensitivity and atrophy progression rate of geographic atrophy secondary to age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70151},
pmid = {41999355},
issn = {1755-3768},
support = {00024226//Velux Fonden/ ; R29-A1337//Region Sjælland/ ; //Fight for Sight Denmark/ ; //Synoptik-Fonden/ ; //Dagmar Marshalls Fond/ ; //Grosserer L. F. Foghts Fond/ ; },
abstract = {PURPOSE: To determine the relationship between the baseline junctional retinal sensitivity measured with microperimetry and the atrophy progression rate in eyes with geographic atrophy (GA) secondary to age-related macular degeneration.

METHODS: In this prospective cohort study, patients with GA were examined with fundus autofluorescence (FAF) to determine the atrophy area at baseline and at follow-up of 13.1 ± 2.5 months in order to determine the atrophy progression rate. Microperimetry and optical coherence tomography (OCT) were evaluated at baseline. Microperimetry was superimposed on the baseline FAF image to determine mean junctional sensitivity. Multivariable linear regression was performed adjusting for age, presence of junctional intraretinal hyperreflective foci (HRF), subretinal drusenoid deposits (SDD) and FAF pattern.

RESULTS: Fifty-six eyes with GA of 56 patients were included. There was a significant association between baseline junctional sensitivity and the atrophy progression rate in GA eyes (β, -8.84 μm/year/dB; 95% CI, -16.56 to -1.11; p = 0.026) tested with simple linear regression. However, when adjusting for age, structural factors and junctional FAF patterns in a multivariable linear regression model, the association between junctional sensitivity and atrophy progression rate was no longer statistically significant (β, -6.40 μm/year/dB; 95% CI, -16.04 to 3.25; p = 0.18). The diffuse trickling FAF pattern was independently and significantly associated with progression rate (p = 0.019).

CONCLUSIONS: Microperimetric junctional sensitivity may have relevance in predicting atrophy progression rate in eyes with GA, although the FAF pattern may be of greater importance. Larger, longitudinal studies are necessary to further elucidate this relationship.},
}

@article {pmid41999445,
year = {2026},
author = {Pearce, I and Dinah, C and Downey, L and Patwardhan, A and Vardarinos, A and Williams, G},
title = {Faricimab in Treatment-Naïve nAMD: Regional UK Real-World Experience.},
journal = {Advances in therapy},
volume = {},
number = {},
pages = {},
pmid = {41999445},
issn = {1865-8652},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a progressive retinal disease leading to significant vision loss. Previous standard of care, anti-vascular endothelial growth factor (anti-VEGF) monotherapy, requires frequent injections to maintain efficacy. Faricimab, which targets angiopoietin-2 and VEGF-A, has shown efficacy in patients with nAMD with extended dosing intervals in randomised controlled trials (RCTs). However, results from RCTs are often challenging to replicate in real-world practice. This study aimed to explore outcomes in patients with nAMD treated with faricimab in real-world settings in the UK.

METHODS: Newly diagnosed patients with nAMD receiving first-line faricimab between 2022 and 2024 were examined across six UK sites in England and Wales. Patients were generally treated per the National Institute of Health and Care Excellence (NICE)-recommended protocol for approximately 1 year, with some deviations at individual sites. Outcomes reported included best-corrected visual acuity (BCVA), optical coherence tomography (OCT) fluid, retinal thickness, treatment intervals and safety. Data were analysed separately for each site; adverse event incidence was pooled.

RESULTS: The total number of eyes treated was 505 from 473 patients. Baseline characteristics were similar across sites, with a mean age of 77.0-82.0 years. BCVA, OCT fluid and retinal thickness improvements from baseline were observed across all sites, irrespective of timepoint or treatment protocol. BCVA improvements from baseline ranged from + 5.1 to + 7.7 letters at the first post-loading visit and from + 5.0 to + 8.2 letters at 12 months. Mean change in retinal thickness from baseline ranged from - 92.3 to - 127.7 μm at 12 months. Most patients received faricimab at intervals of ≥ 8 weeks following the loading phase. The pooled incidence of adverse events was low.

CONCLUSION: Faricimab demonstrated consistent visual and anatomical improvements in real-world UK settings across a heterogeneous group of patients with nAMD. Further real-world studies will be essential to confirm long-term safety and effectiveness in clinical practice.},
}

@article {pmid41999903,
year = {2026},
author = {Domalpally, A and Chew, EY and Eydelman, MB and Keenan, TDL and Keane, PA and Lee, AY and Lee, CS and Lad, EM and Lim, JI and Lowenstein, A and Schmidt-Erfurth, U and Abramoff, MD and , },
title = {Reference Standard for Validation of Age-Related Macular Degeneration Screening Algorithms.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.04.013},
pmid = {41999903},
issn = {1549-4713},
abstract = {PURPOSE: Artificial intelligence (AI)-based screening models hold promise for identifying individuals with undiagnosed age-related macular degeneration (AMD) in non-specialist settings. A standardized reference framework for image labeling is needed to enable consistent training, validation, and deployment of AI based screening algorithms.The goal of the present study is to establish expert consensus on image -based reference standard for labeling AMD DESIGN: Modified Delphi consensus study Subjects/ Participants: fellowship-trained retina specialists, ophthalmologists, AI specialists, and imaging specialists METHODS: A prespecified Delphi process was conducted using structured surveys . Over two rounds, panelists assessed opinions on existing reference standards, including the AREDS scale and Beckman scale, as well as imaging modalities such as color, optical coherence tomography (OCT), and autofluorescence. The surveys also evaluated imaging features of AMD, including drusen, pseudodrusen, and pigment changes, as well as referral criteria. Consensus was defined using a 9-point Likert scale, with predefined statistical thresholds for agreement.

MAIN OUTCOME MEASURES: Agreement on key elements of a reference standard RESULTS: Consensus was reached on adopting the Beckman Classification as the level 1 reference standard (median score 8; agreement). OCT use for identifying key AMD features, including drusen, GA, and CNV, also reached consensus (median scores 8.5-9; agreement). Pigment change detection did not reach consensus (median 7.5; uncertain), and screening age thresholds showed non-consensus (median 8; uncertain). Referral thresholds reached consensus, including urgent referral for neovascular AMD and non-urgent referral for GA and intermediate AMD (median 9; agreement).

CONCLUSIONS: This study defines a consensus-based reference standard for labeling AMD from images for AI based screening. These recommendations are intended to support consistent AI model development and evaluation, while remaining distinct from clinical practice guidelines.},
}

@article {pmid41992419,
year = {2026},
author = {Chen, YS and Chang, HC and Chi, SC and Tanaka, K and Chen, SJ and Lin, TC},
title = {Different aflibercept regimens for wet age-related macular degeneration: A systematic review and network meta-analysis.},
journal = {Journal of the Chinese Medical Association : JCMA},
volume = {},
number = {},
pages = {},
doi = {10.1097/JCMA.0000000000001379},
pmid = {41992419},
issn = {1728-7731},
abstract = {BACKGROUND: Intravitreal aflibercept injection for wet age-related macular degeneration (AMD) was initially approved with a regimen consisting of three monthly loading doses followed by maintenance doses every 8 weeks. Alternative regimens with a reduced treatment burden have been explored. The treat-and-extend (TAE) regimen involves gradually extending the treatment interval in accordance with disease activity, and the pro re nata (PRN) regimen involves administering injections only when signs of disease activity are observed during follow-up visits. This study evaluated these alternative regimens aimed at reducing treatment burden in real-world clinical practice.

METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Web of Science databases for relevant randomized controlled trials (RCTs). A random-effects model was adopted for network meta-analysis. Results are presented as standardized mean differences (SMDs) with corresponding 95% confidence intervals (CIs). Methodological quality of the included RCTs was assessed using the Cochrane risk-of-bias 2.0 tool.

RESULTS: Seven RCTs (1,683 patients with wet AMD) were included in the network meta-analysis. No significant interregimen differences were observed in visual acuity or central retinal thickness. The TAE and PRN regimens required significantly fewer injections than did bimonthly and monthly regimens, respectively (TAE vs. bimonthly: SMD -1.091, 95% CI -2.030 to -0.153; TAE vs. monthly: SMD -3.024, 95% CI -4.584 to -1.465; PRN vs. Bimonthly: SMD -1.919, 95% CI -3.307 to -0.532; PRN vs. Monthly: SMD -3.852, 95% CI -5.717 to -1.988). However, injection count did not differ significantly between the TAE and PRN regimens (TAE vs. PRN: SMD 0.828, 95% CI -0.847 to 2.503). Nonetheless, the TAE regimen was associated with fewer clinic visits than the PRN regimen.

CONCLUSION: The TAE regimen maintains efficacy while reducing treatment burden in patients with wet AMD receiving intravitreal aflibercept.},
}

@article {pmid41993457,
year = {2026},
author = {Cakir, B and Yeh, TC and Lin, CH and Wu, MR and Boilard, É and Pelletier, M and Singh, AM and Breton, Y and Patel, S and Benson, T and Almeida, DR and Wang, S and Mahajan, VB},
title = {Mitochondrial Transplantation in the Eye: A Review and Evaluation of Surgical Approaches.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.06.716722},
pmid = {41993457},
issn = {2692-8205},
abstract = {PURPOSE: Mitochondrial dysfunction contributes to major blinding diseases, including age-related macular degeneration and glaucoma. Although mitochondrial transplantation has shown therapeutic potential in multiple organ systems, translation to the eye remains limited, partly due to uncertainty regarding optimal delivery. We summarize the biologic rationale and preclinical evidence supporting ocular mitochondrial transplantation and present feasibility data evaluating clinically relevant delivery routes.

METHODS: We conducted a focused narrative review of ocular mitochondrial transplantation. For feasibility experiments, mitochondria with an endogenous fluorescent dye were isolated from liver donor mice. Postnatal day 7 pups received subretinal injections, and adult CD1 mice received intravitreal injections, including optic nerve head directed delivery. Eyes were analyzed using fluorescence microscopy and immunohistochemistry. Mitochondrial uptake was assessed in cultured retinal pigmental epithelial (RPE) cells using co-incubation assays. Suprachoroidal delivery feasibility was evaluated in cadaveric human near-real surgical specimens using a novel dedicated suprachoroidal injector.

RESULTS: The literature on ocular mitochondrial transplantation remains limited and consists primarily of small preclinical studies using intravitreal delivery and imaging-based detection. In our experiments, intravitreal delivery produced donor signals predominantly within inner retinal layers, with enrichment along retinal nerve fiber bundles when directed toward the optic nerve head. Cultured RPE cells demonstrated dose-dependent uptake of exogenous mitochondria. Subretinal delivery localized donors signal to the RPE and adjacent outer retina. Suprachoroidal injections demonstrated procedural feasibility with reliable access to the suprachoroidal space and visible injectate distribution.

CONCLUSIONS: Ocular mitochondrial transplantation is in an early stage of investigation. Our feasibility data indicate that established posterior-segment delivery routes expose distinct retinal compartments and that route selection strongly influences anatomic distribution. Further studies are needed to verify intracellular uptake, define dosing and durability, and evaluate safety in disease-relevant models.},
}

@article {pmid41993761,
year = {2026},
author = {Bousamri, A and Al-Shehri, M and Mestarihi, M and Almutairi, TB and Alaredhi, M and Mahanna, B and Alharbi, F},
title = {Clinical Outcomes of High-Dose Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: A Systematic Review and Meta-Analysis.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106769},
pmid = {41993761},
issn = {2168-8184},
abstract = {Polypoidal choroidal vasculopathy (PCV) is a distinct subtype of neovascular macular disease with variable responses to anti-vascular endothelial growth factor (anti-VEGF) therapy. This systematic review and meta-analysis evaluated the visual, anatomical, and lesion-regression outcomes of intravitreal aflibercept 8 mg, a formulation developed to extend dosing intervals while maintaining efficacy, in patients with PCV. PubMed, Embase, Scopus, Web of Science, and Google Scholar were searched from inception to March 12, 2026 (PROSPERO: CRD420261339679). Eligible studies enrolled adults with indocyanine green angiography (ICGA)-confirmed PCV treated with aflibercept 8 mg and reported at least one co-primary outcome: change in best-corrected visual acuity (BCVA), central retinal or subfield thickness (CRT/CST), or complete polyp regression. Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB 2), Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I), and Joanna Briggs Institute (JBI) appraisal tools. Complete polyp regression was analyzed using a generalized linear mixed model with a logit link; continuous outcomes were pooled using restricted maximum likelihood estimation with the Hartung-Knapp-Sidik-Jonkman correction. Certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. Five studies encompassing 362 eyes (245 treated with aflibercept 8 mg) were included. The pooled complete polyp regression rate was 57% (95% confidence interval (CI), 39%-73%; I[2]=55.9%; k=3). The pooled mean CRT/CST change was -157.8 µm (95% CI, -176.9 to -138.7 µm; I[2]=0%; k=2), though the estimate was predominantly driven by a single study contributing 95.5% of the inverse-variance weight. BCVA outcomes were not pooled due to metric incompatibility and clinical heterogeneity; however, individual study results were directionally favorable, with Early Treatment Diabetic Retinopathy Study (ETDRS) gains of +8.4 to +9.5 letters at 48 weeks in the largest contributing study. Extended dosing intervals were maintained in 80.5% (q12) and 86.5% (q16) of treated eyes at 48 weeks. One study reported intraocular inflammation in 10.8% of the overall neovascular age-related macular degeneration (AMD) cohort in that study, a safety signal not observed in the remaining studies. The certainty of evidence was low for CRT/CST change and very low for polyp regression and BCVA. Available evidence suggests that aflibercept 8 mg may produce clinically relevant polyp regression and substantial anatomical improvement in PCV, with a potential reduction in injection frequency. However, given the low to very low certainty of the current evidence base across all co-primary outcomes, definitive efficacy and safety conclusions cannot yet be drawn. Prospective, PCV-specific trials with standardized outcome reporting are needed.},
}

@article {pmid41994559,
year = {2026},
author = {Cheng, CK and Tsai, CJ and Bai, CH},
title = {Reassessing high-dose ranibizumab in the era of durable anti-VEGF therapy.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1802903},
pmid = {41994559},
issn = {2674-0826},
}

@article {pmid41995082,
year = {2026},
author = {Patel, MK and Piedade, WP and Famulski, JK},
title = {Cdhr1a and pcdh15b may link photoreceptor outer segments with calyceal processes revealing a potential mechanism for cone-rod dystrophy.},
journal = {eLife},
volume = {13},
number = {},
pages = {},
doi = {10.7554/eLife.102258},
pmid = {41995082},
issn = {2050-084X},
support = {P20GM103436//KYINBRE core facility voucher/ ; },
mesh = {Animals ; *Cadherins/metabolism/genetics ; Zebrafish ; Humans ; *Cone-Rod Dystrophies/pathology/genetics/metabolism ; Cadherin Related Proteins ; *Zebrafish Proteins/metabolism/genetics ; Mice ; *Retinal Photoreceptor Cell Outer Segment/metabolism ; },
abstract = {Cone-rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell degeneration. Mutations in CDHR1, a photoreceptor-specific cadherin, have been found to be associated with the incidence of CRD. While studying the function of CDHR1, we observed that the localization of the zebrafish homologue, cdhr1a, resembles that of calyceal process (CPs). When co-labeling CPs using pcdh15b, we observed that cdhr1a, in the outer segment (OS), juxtaposes with pcdh15b, found in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, gerbil, and mouse. Using immunoprecipitation and K652 cell aggregation assays, we demonstrate that pcdh15b and cdhr1a can interact and thus potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a cdhr1a mutant line (cdhr1a[fs*146]). Homozygous cdhr1a[fs*146] mutants exhibit minor cone OS defects starting at 15 dpf and severe OS disruption and cell loss by 3 months. Shortening of CPs coincided with cone OS defects which were significantly exacerbated when combined with the loss of pcdh15b. Rod OS defects were mild and delayed until 3-6 months. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs and maintain OS integrity.},
}

Animals
*Cadherins/metabolism/genetics
Zebrafish
Humans
*Cone-Rod Dystrophies/pathology/genetics/metabolism
Cadherin Related Proteins
*Zebrafish Proteins/metabolism/genetics
Mice
*Retinal Photoreceptor Cell Outer Segment/metabolism

@article {pmid41995436,
year = {2026},
author = {Pu, J and Zhuang, X and Hao, X and Li, M and Su, Y and He, G and He, Y and Zhang, G and Wen, F},
title = {Longitudinal Tracking of Photoreceptor Integrity in Neovascular AMD: Early Restoration Predicts 24-Month Structural and Visual Outcomes.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {41},
doi = {10.1167/iovs.67.4.41},
pmid = {41995436},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Aged ; Prospective Studies ; *Visual Acuity/physiology ; Tomography, Optical Coherence/methods ; *Angiogenesis Inhibitors/therapeutic use/administration & dosage ; *Wet Macular Degeneration/drug therapy/physiopathology/diagnosis ; Follow-Up Studies ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Intravitreal Injections ; Fluorescein Angiography ; *Photoreceptor Cells, Vertebrate/pathology ; Ranibizumab/therapeutic use/administration & dosage ; Time Factors ; },
abstract = {PURPOSE: The purpose of this study was to longitudinally characterize photoreceptor band changes over 24 months and determine whether early restoration predicts long-term outcomes in neovascular age-related macular degeneration (nAMD).

METHODS: This prospective study enrolled treatment-naïve patients with nAMD receiving anti-vascular endothelial growth factor therapy following 3 + pro re nata (PRN) regimen. Impaired areas of outer nuclear layer (ONL), ellipsoid zone (EZ), external limiting membrane (ELM), and interdigitation zone (IZ) were quantified at baseline, 1 week, 1, 2, 3, 12, and 24 months, and associations between early restoration and long-term structural and visual outcomes were assessed.

RESULTS: Eighty-two eyes from 82 patients (mean age = 65.15 ± 7.47 years) completed a 24-month follow-up. All bands showed significant changes over 2 years (P < 0.05 for all). Only EZ demonstrated significant early restoration at 1 week and 1 month (P = 0.041 and 0.004, respectively). Month 3 restoration of all bands predicted corresponding 1- and 2-year structural changes (Stdβ = 0.432-0.912, P < 0.05, except for 2-year ONL and IZ: P = 0.201 and 0.304, respectively). Moreover, month 2 ONL changes also independently predicted long-term ONL changes (P = 0.011 and P < 0.001 for 1 and 2 years, respectively). For visual outcomes, month 3 IZ restoration predicted 1-year BCVA improvement (Stdβ = -0.334, P = 0.032), whereas month 2 ONL restoration predicted 2-year BCVA improvement (Stdβ = -0.378, P = 0.003).

CONCLUSIONS: Photoreceptor bands showed layer-specific restoration patterns, with EZ responding earliest. Early restoration at months 2 to 3 predicted long-term outcomes, with ONL and IZ as independent visual predictors.},
}

Humans
Female
Male
Aged
Prospective Studies
*Visual Acuity/physiology
Tomography, Optical Coherence/methods
*Angiogenesis Inhibitors/therapeutic use/administration & dosage
*Wet Macular Degeneration/drug therapy/physiopathology/diagnosis
Follow-Up Studies
Middle Aged
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Intravitreal Injections
Fluorescein Angiography
*Photoreceptor Cells, Vertebrate/pathology
Ranibizumab/therapeutic use/administration & dosage
Time Factors

@article {pmid41998200,
year = {2026},
author = {Cheah, IK and Fong, ZW and Chen, L and Tang, RMY and Zhou, L and Yanagi, Y and Cheng, CY and Su, X and Li, X and Teo, KYC and Cheung, CMG and Tan, TE and Halliwell, B},
title = {Ergothioneine as a potential protective agent against macular degeneration and other eye disorders.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-48438-x},
pmid = {41998200},
issn = {2045-2322},
support = {OFYIRG22jul-0027//National Medical Research Council/ ; R1752/75/2020//SERI Lee Foundation Grant/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in ageing populations, with oxidative stress recognised as a key pathogenic driver. The dietary antioxidant and cytoprotectant, L-ergothioneine (ET), is avidly accumulated in many tissues, especially the eye. However its relationship to AMD is unclear. Here, we examined ET's distribution in human ocular tissues and measured serum and intraocular ET levels in patients with neovascular AMD. Compared with ocularly-normal age-matched individuals, AMD patients exhibited significantly lower serum ET; elevated levels of ET metabolites, hercynine and ETSO3, which may be generated by oxidative stress; and elevated levels of serum allantoin, a biomarker of oxidative damage to urate in humans. Levels of ET in aqueous humour in AMD patients were marginally lower than cataractous patients, who are already known to have significantly lower ET levels than healthy eyes. High ET levels were seen in human ocular tissues, concentrating in regions vulnerable to oxidative damage, including the lens, retina, retinal pigment epithelium, and choroid, supporting a physiological protective role of ET in the eye. These findings identify a strong association between low ET levels and AMD, warranting further studies to determine whether ET supplementation can modify AMD risk or progression.},
}

@article {pmid41998289,
year = {2026},
author = {Küçükerdönmez, C and Tedford, SE},
title = {Response to "Letter to the Editor Regarding 'Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration'".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40123-026-01383-4},
pmid = {41998289},
issn = {2193-8245},
}

@article {pmid41998290,
year = {2026},
author = {Karakosta, C and MacLaren, RE},
title = {Letter to the Editor Regarding "Multiwavelength Photobiomodulation Improves Multiple Aspects of Visual Function in Early-Stage Dry Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41998290},
issn = {2193-8245},
}

@article {pmid41987023,
year = {2026},
author = {Horita, S and Saki, M and Takigawa, S and Kanai, Y and Murotani, K and Gomi, F},
title = {Ocular pharmacokinetics of tivozanib eye drops in patients with neovascular age-related macular degeneration: comparison with phase 1 trials of oral tivozanib in solid tumors.},
journal = {International journal of retina and vitreous},
volume = {12},
number = {1},
pages = {},
pmid = {41987023},
issn = {2056-9920},
abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD) but is invasive and burdensome for patients. To overcome these obstacles, tivozanib, a pan-VEGF receptor inhibitor approved for renal cell carcinoma, is in development as eye drops. The phase 1 study of a 3-week administration of tivozanib eye drops showed a preferable safety profile and exploratory efficacy signs in Japanese patients with nAMD. During eye drop administration, two drug delivery pathways affect ocular pharmacokinetics, either directly through the ocular tissues or through systemic circulation. To assess the ocular pharmacokinetics of tivozanib eye drops, we conducted an integrated analysis of systemic adverse event occurrence and systemic exposure in patients with nAMD treated with tivozanib eye drops and in patients with cancer treated with oral tivozanib, using previous phase 1 study results. Systemic exposure was significantly lower with tivozanib eye drops versus oral tivozanib, with no drug-related hypertension due to the systemic pan-VEGF receptor inhibition observed, suggesting systemic VEGF receptors are not fully inhibited by tivozanib. Exploratory efficacy signs in patients with nAMD after short-term use of tivozanib eye drops also suggest tivozanib might reach the retina and inhibit VEGF receptors, although further long-term efficacy studies are warranted. Given the integrated analysis, we hypothesize that tivozanib eye drops could predominantly be delivered to the posterior eye segment through the ocular tissues, with limited contribution by the systemic drug delivery pathway. This hypothesis provides meaningful insights into the ocular pharmacokinetics of tivozanib eye drops.},
}

@article {pmid41987034,
year = {2026},
author = {Mohamed, MI and Halwag, MI and Mahmoud, NH and Salib, M and Nada, MA},
title = {Migraine as a risk factor for retinal vascular events and maculopathies: a systematic review and meta-analysis of 47 million individuals.},
journal = {The journal of headache and pain},
volume = {},
number = {},
pages = {},
doi = {10.1186/s10194-026-02353-8},
pmid = {41987034},
issn = {1129-2377},
}

@article {pmid41987176,
year = {2026},
author = {Zhang, Y and He, W and Wang, C and Liu, B and Wen, J and Zhao, Y and Zhang, Y and Liu, L and Yang, Q and Li, J and Dong, Y and Zhang, X and Xu, Q and Zhai, G and Ye, L and Qu, Y},
title = {A sequential dual-drug delivery system for multi-target inhibition of subretinal fibrosis.},
journal = {Journal of nanobiotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12951-026-04390-6},
pmid = {41987176},
issn = {1477-3155},
abstract = {BACKGROUND: Subretinal fibrosis (SRF), a severe vision-threatening complication secondary to neovascular age-related macular degeneration (nAMD), remains a major clinical challenge due to its complex pathogenesis and prolonged disease course. The fibrotic process is driven by multiple synergistic factors, including chronic inflammation, hypoxia, epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, and pathological neovascularization, which collectively lead to the ineffectiveness of conventional anti-vascular endothelial growth factor (VEGF) monotherapies in halting disease progression.

RESULTS: This study developed a sequential dual-drug delivery system based on the terpolymer P(NIPAM-co-AA-co-HEMA) hydrogel (NAHGel), designed to achieve multi-targeted regulation from the pathological microenvironment to downstream fibrotic processes. NAHGel exhibits excellent thermal responsiveness, biomechanical stability, and biodegradability, and is co-loaded with matrine (MT) and cRGD-modified sorafenib liposomes (SF/cLP). The hydrogel undergoes thermal contraction to enable the rapid release of hydrophilic MT, exerting anti-inflammatory and anti-hypoxic effects. As the hydrogel progressively degrades, SF/cLP is released in a delayed manner and, under cRGD mediation, is targeted to RPE cells and vascular endothelial cells. This enables modulation of key pathways including TGF-β2/MEK1/2/ERK1/2 and HIF-α/VEGF/PDGF, thereby inhibiting EMT and endothelial proliferation. In a laser-induced SRF mouse model, MT + SF/cLP@NAHGel formed a stable in situ gel within 24 h after intravitreal injection and remained structurally intact in the dynamic vitreous environment, enabling sustained retention for up to 8 months. Imaging and histological analyses demonstrated that, compared with aflibercept and other group, this system significantly reduced choroidal neovascularization and fibrotic lesion areas. Transcriptomic analysis further confirmed its broad inhibition of signaling pathways related to inflammation, angiogenesis, and fibrosis, with marked downregulation of key mediators including VEGFA, TGF-β2, TNF-α, and HIF-1α.

CONCLUSION: MT + SF/cLP@NAHGel achieves sequential drug release and multi-targeted synergy to intervene in key pathological processes such as inflammation, hypoxia, EMT, and pathological neovascularization, thereby effectively halting SRF progression. Combining sustained therapeutic efficacy with excellent biosafety, this system holds strong translational potential as a long-acting treatment strategy for SRF and other multifactorial retinal diseases.},
}

@article {pmid41987778,
year = {2026},
author = {Li, M and Gu, A and Li, H and Li, Y and Liang, R and Su, T and Wu, Y},
title = {Machine-learning for age-related macular degeneration using multimodal fundus data.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1756787},
pmid = {41987778},
issn = {2296-858X},
abstract = {OBJECTIVE: To develop an integrated model that combines multimodal fundus image features for accurately predicting the individualized risk of progression from early to late stages of age-related macular degeneration (AMD).

METHODS: A retrospective analysis was conducted on the data of 324 patients with AMD. The patients were randomly divided into a training set (n = 227) and a validation set (n = 97) at a ratio of 7:3. The follow-up period was 3 years, and patients with disease progression were defined as the progression group. In the training set, indicators related to prognosis were screened through univariate analysis. After variable compression by LASSO regression, independent influencing factors for poor prognosis were determined using multivariate logistic regression. Random Forest, Support Vector Machine, XG BOOST, and K-Nearest Neighbor algorithm prediction models were constructed using Python software. The performance of the models was evaluated by the area under the receiver operating characteristic curve (AUC), and the optimal model was selected.

RESULTS: There were no significant differences in the baseline characteristics between the training set and the validation set patients (P > 0.05), indicating comparability. In the training set, multivariate logistic regression analysis showed that pigmentary abnormalities, the total area of drusen in the macular area, and the ellipsoid zone were independent risk factors for disease progression (P < 0.05), while subfoveal choroidal thickness and choroidal capillary blood flow density were independent protective factors (P < 0.05). The AUC values of the Random Forest model (0.779 in the training set and 0.700 in the validation set) were significantly higher than those of the K-Nearest Neighbor algorithm (0.717 in the training set and 0.596 in the validation set), the Support Vector Machine model (0.768 in the training set and 0.646 in the validation set), and XG BOOST (0.702 in the training set and 0.762 in the validation set), making it the optimal prediction model.

CONCLUSION: In this study, an AMD progression prediction model based on multimodal fundus images was successfully developed, which can effectively identify patients at high risk of progression and provide a new paradigm for clinical individualized precision medicine.},
}

@article {pmid41987800,
year = {2026},
author = {Garcia-Atutxa, I and Martinez-Baliu, L and Villanueva-Flores, F},
title = {Robust benchmarking of DeepLabv3 hybrid models for multiclass fundus screening and referable-disease triage on the FIVES dataset.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1771083},
pmid = {41987800},
issn = {2296-858X},
abstract = {BACKGROUND: Automated analysis of color fundus photographs can support scalable screening for diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, but single-run reporting and accuracy-only summaries can mask clinically relevant instabilities and failure modes.

METHODS: Using the public FIVES dataset, we benchmarked six deep learning configurations for four-class fundus screening (AMD, DR, glaucoma, normal): three DeepLabv3-backbone hybrids (ResNet50, DenseNet121, EfficientNet-B0) and three backbone-only classifiers. All experiments were evaluated using five independent stratified splits generated with different random seeds (n = 5 runs), each defining a distinct 20% held-out test set. Models were trained on the remaining 80% (training/validation), and all reported metrics are computed on the 20% test set of each run and summarized as mean ± SD across runs. Performance was summarized with accuracy, sensitivity, specificity, and one-vs.-rest AUC; we further characterized clinical behavior via row-normalized confusion matrices, per-class precision/recall/F1, and a screening-style binary triage setting (referable = AMD ∪ DR ∪ glaucoma vs. normal).

RESULTS: Hybrid models consistently achieved higher discrimination than simple classifiers (AUC 0.969-0.979 vs. 0.908-0.920), despite similar accuracies (0.924-0.941). The selected model, DeepLabv3-DenseNet121, reached the highest AUC (0.979 ± 0.009). Class-wise analysis revealed strong performance for Normal (F1 0.970 ± 0.014) and Glaucoma (F1 0.896 ± 0.048), while DR was the main bottleneck (sensitivity 0.738 ± 0.117), with most DR errors redistributed to AMD (13.6%) and Glaucoma (12.0%) and minimal confusion with Normal (0.5%). In binary triage, the model achieved sensitivity 0.993 ± 0.011 and specificity 0.963 ± 0.034, with PPV 0.987 ± 0.013 and NPV 0.980 ± 0.032, and a stable referral rate (∼0.73-0.77) across runs.

CONCLUSION: DeepLabv3-based hybrids provide a robust advantage in AUC for multiclass fundus screening on FIVES. The residual risk concentrates in the DR-AMD-Glaucoma decision boundary, suggesting that deployment-oriented policies should prioritize conservative handling of DR-adjacent cases while leveraging the stability of Normal predictions for screening workflows.},
}

@article {pmid41988431,
year = {2026},
author = {Auer, EA and Gnanaraj, R and Lynch, AM and Mandava, N and Palestine, AG and Mathias, MT and Manoharan, N and Lisker-Cervantes, A and de Carlo Forest, TE and Kohrt, WM and Patnaik, JL},
title = {Menopausal Hormone Therapy and Conversion from Intermediate to Advanced Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261428770},
pmid = {41988431},
issn = {2474-1272},
abstract = {Purpose: To evaluate the relationship between self-reported menopausal hormone replacement therapy use and conversion to an advanced form of AMD among female patients with intermediate AMD (iAMD). Methods: Female patients with iAMD enrolled in the University of Colorado AMD Registry between July 2014 and July 2024 were included in this prospective cohort study, with follow-up through November 2024. Conversion to an advanced form of AMD, either advanced non-neovascular AMD or neovascular AMD, was assessed by review of patients' multimodal imaging. Kaplan-Meier curves and Cox proportional hazards modeling were used to assess time to conversion. Hazard ratios (HRs) with 95% CIs are presented for multivariable models. Results: Among 285 female patients with iAMD, the mean (±SD) follow-up time was 36.3 ± 26.7 months. In a total of 82 patients (28.8%), conversion to advanced AMD occurred during follow-up. In univariate analysis, a history of ever having used hormone replacement therapy (55.4%), compared with never having used hormone replacement therapy (44.6%), was not associated with conversion to either of the advanced forms of AMD. In multivariable analysis, patients who had ever used hormone replacement therapy did not have significantly elevated risks of conversion to advanced non-neovascular AMD (HR, 1.03, 95% CI, 0.54-1.96; P = .94) or neovascular AMD (HR, 2.10, 95% CI, 0.86-5.02; P = .10). Conclusions: Among female patients with iAMD, self-reported use of hormone replacement therapy was not associated with an increased risk of conversion to either of the advanced forms of AMD.},
}

@article {pmid41988735,
year = {2026},
author = {Sun, H and Gao, E and Li, Y and Xiang, D and Lu, F and Zhou, Y and Zhu, W and Shi, F and Nie, B and Chen, X and Zhang, L and Cai, J and Peng, D and Peng, T},
title = {Refining feature representation for accurate fundus lesion segmentation.},
journal = {Medical physics},
volume = {53},
number = {4},
pages = {e70441},
doi = {10.1002/mp.70441},
pmid = {41988735},
issn = {2473-4209},
support = {62371328//National Nature Science Foundation of China/ ; 61971298//National Nature Science Foundation of China/ ; 62371326//National Nature Science Foundation of China/ ; 62271337//National Nature Science Foundation of China/ ; 62471326//National Nature Science Foundation of China/ ; BK20231310//Natural Science Foundation of Jiangsu Province/ ; 24KJB510042//Natural Science Foundation of the Jiangsu Higher Education Institutions of China/ ; JSTJ-2024-434//Technology Young Science and Technology Talent Support Project/ ; PRJ2022008//DKU Education Development Fund/ ; },
mesh = {*Image Processing, Computer-Assisted/methods ; Humans ; *Fundus Oculi ; Deep Learning ; Choroidal Neovascularization/diagnostic imaging ; Macular Degeneration/diagnostic imaging ; Retina/diagnostic imaging ; },
abstract = {BACKGROUND: Accurate segmentation of retinal lesions is essential for early detection of age-related macular degeneration (AMD), particularly its key indicators, choroidal neovascularization (CNV) and choroidal non-perfusion (CNP). However, the highly variable shapes and appearances of lesions pose substantial challenges for automated segmentation.

PURPOSE: To tackle these challenges, we propose a deep-learning model, the Retinal Feature Enhancement Network (RFENet), designed to improve the accuracy and robustness of retinal lesion segmentation under challenging imaging conditions.

METHODS: RFENet builds upon the UNeXt backbone and introduces two modules tailored for retinal lesion segmentation: an Adaptive Feature Refinement Unit (AFRU), which selectively emphasizes informative features, and an Optimized Channel-Wise Convolution Unit (OCCU), which captures fine structural details in irregular lesions. Two expert-annotated datasets were used: 1070 OCT B-scans from 83 CNV patients and 184 FFA images from 107 CNP patients. Images were split at the patient level into training (70%), validation (10%), and test (20%) sets. Performance was compared against state-of-the-art segmentation models, including UNet++, Swin-UNet, SelfReg-UNet, DAEFormer, and Mamba-UNet. Evaluation metrics included Dice coefficient and Intersection over Union (IoU). Statistical significance was assessed using paired two-tailed t-tests (α = 0.05 $\alpha = 0.05$), and effect sizes were reported with Cohen's d $d$ .

RESULTS: On the CNV dataset, RFENet achieved a Dice of 82.50% and an IoU of 71.66%, with clear improvements over competing models. On the CNP dataset, RFENet achieved a Dice of 74.43% and an IoU of 60.80%, slightly surpassing the best benchmark. Most pairwise comparisons were statistically significant, including CNV compared with Swin-UNet and SelfReg-UNet (p < $<$ 0.001) and CNP compared with DAEFormer (p = $=$ 0.035). Statistical analyses, including effect size evaluation, further confirmed the robustness of these improvements, with the most notable gains observed in the CNV dataset.

CONCLUSIONS: RFENet demonstrated consistent improvements over strong benchmarks on both CNV and CNP tasks, with statistical evidence supporting the reliability of these gains. These results indicate that RFENet provides a reliable technical advance for automated segmentation of CNV and CNP lesions associated with AMD. To facilitate reproducibility and further research, the source code is publicly available at https://github.com/HaoSun223/RFENet.},
}

*Image Processing, Computer-Assisted/methods
Humans
*Fundus Oculi
Deep Learning
Choroidal Neovascularization/diagnostic imaging
Macular Degeneration/diagnostic imaging
Retina/diagnostic imaging

@article {pmid41989239,
year = {2026},
author = {Jonas, JB and Panda-Jonas, S and Jonas, RA and Wang, YX},
title = {Prevalence and associations of hyper-reflective bodies in the posterior vitreous: The Beijing eye study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70139},
pmid = {41989239},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; },
abstract = {PURPOSE: To assess prevalence and associations of intra-vitreal hyper-reflective bodies (vHRBs) in the posterior vitreous in a general population.

METHODS: Participants of the population-based Beijing Eye Study underwent systemic and ophthalmological examinations. We included into this study a randomly selected group of normal eyes without retinal diseases and a randomly selected group of eyes with age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PVC) or central serous choroidopathy (CSC). Using serial optical coherence tomography scans of the posterior fundus region, we searched for vHRBs in the posterior vitreous compartment.

RESULTS: The study consisted of 1347 eyes (age: 64.3 ± 9.8 years, range: 50-91 years; axial length: 23.04 ± 1.00 mm, range: 19.39-28.93 mm). vHRB were detected in 314/1347 eyes (23.3%; 95% confidence interval [CI]: 21.1, 25.6), that is, in 137 out of 447 normal eyes (28.9%; 95% CI: 24.8, 33.0), 110/458 eyes with early AMD (24.0%; 95% CI: 20.1, 27.9), 45/278 eyes with intermediate AMD (16.2%; 95% CI: 11.8, 20.5), 3/35 eyes with PCV (8.6%; 95% CI: 0.00, 18.3), and in 19/94 eyes with CSC (20.2%; 95% CI: 11.9, 28.5). In multivariable analysis, higher vHRB prevalence was associated with younger age (OR: 0.93; 95% CI: 0.91, 0.95; p < 0.001), shorter axial length (OR: 0.69; 95% CI:0.56, 0.84; p < 0.001), and lower stage of posterior vitreous detachment (OR: 0.53; 95% CI: 0.44, 0.64; p < 0.001). It was independent of AMD stage (p = 0.87), and prevalence of PCV (p = 0.67) and CSC (p = 0.40). Higher amount of vHRBs (multivariable linear regression analysis) correlated with younger age (beta: -0.21; B: -0.02; 95% CI: -0.03, -0.02; p < 0.001), shorter axial length (beta: -0.07; B: -0.09; 95% CI: -0.16, -0.02; p = 0.009) and lower stage of posterior vitreous detachment (beta: -0.15; B: -0.13; 95% CI: -0.19, -0.08; p < 0.001).

CONCLUSIONS: vHRBs were detected in one out of four normal eyes of individuals aged 50+ years, in dependence on younger age, shorter axial length and lower degree of posterior vitreous detachment. They were independent of a concurrence of AMD, PCV and CSC.},
}

@article {pmid41989896,
year = {2026},
author = {Wen, Y and Zeng, Y and Bi, L and Zhao, X and Shi, W and Fu, H and Sheng, B},
title = {M2Net: Multimodal Multitask Mutual Learning for Anti-VEGF Efficacy Prediction.},
journal = {IEEE transactions on medical imaging},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TMI.2026.3684331},
pmid = {41989896},
issn = {1558-254X},
abstract = {Age-related macular degeneration with abnormal blood vessel growth (neovascular AMD) is the leading cause of vision loss in elderly populations. While anti-VEGF injections are the standard treatment, they present financial burdens for patients and vary in effectiveness. Predicting treatment efficacy is therefore crucial for patient care. Current prediction methods fail to fully integrate information from different imaging techniques, typically focusing on either forecasting vision improvements or generating post-treatment images-but not both simultaneously. This approach overlooks the important relationship between these tasks. We present M2Net, a novel joint generation and classification network based on Multimodal Multitask Mutual learning, to simultaneously predict changes in visual acuity and generate post-treatment retinal images. M2Net employs a dual-branch structure that processes both fundus photographs and Optical Coherence Tomography (OCT) scans to improve prediction accuracy. Our framework includes two key innovations: the Multimodal Collaborative Treatment Efficacy Prediction module, which interacts the features between the two modalities and provides initial visual acuity change classification to guide the generation of post-treatment images; and the Pre-Post Treatment Image Joint Analysis module, which identifies both common and changing features between pre-treatment and post-treatment images to enhance prediction accuracy. To validate our approach, we created the dataset (MMPD) containing paired multimodal retinal images with corresponding visual acuity measurements. Experiments on the dataset demonstrate that M2Net achieves superior performance compared to existing methods, with a classification accuracy of 96.03%, an SSIM of 0.6377 on the OCT modality, and an SSIM of 0.8347 on the fundus modality. Our code will be available at https://github.com/zengying123/M2Net.},
}

@article {pmid41990324,
year = {2026},
author = {Rhodes, EY and Xia, JL and de Carlo Forest, TE and Manoharan, N and Palestine, AG and Reddy, AK},
title = {Hypertensive Anterior Uveitis Following Intravitreal Faricimab.},
journal = {Ocular immunology and inflammation},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/09273948.2026.2658753},
pmid = {41990324},
issn = {1744-5078},
abstract = {PURPOSE: Describe findings of three cases of culture and PCR negative hypertensive anterior uveitis following intravitreal faricimab.

METHODS: This is a case series of three patients undergoing treatment for diabetic macular edema (DME) or neovascular age-related macular degeneration (nAMD). Data collected included visual acuity, intraocular pressure (IOP), slit lamp examination (SLE), anterior chamber (AC) tap, vitreous tap with culture, and fluorescein angiography (FA).

RESULTS: Three patients developed hypertensive uveitis following repeated intravitreal faricimab injections for DME or nAMD. All presented within 2-5 weeks of injection with ocular pain and redness. Exam revealed elevated intraocular pressure (22-52 mmHg), and keratic precipitates with anterior chamber inflammation. Infectious and inflammatory workups, including aqueous and/or vitreous PCR for HSV, VZV, and CMV, were negative in all cases. Faricimab was discontinued and topical and/or local corticosteroids initiated, with adjunctive IOP-lowering therapy as indicated. Inflammation resolved in all patients within 3 months without recurrence after switching intravitreal anti-VEGF agents. Final visual acuity ranged from 20/25 to count fingers, limited by glaucomatous optic neuropathy in one case.

CONCLUSIONS: Hypertensive anterior uveitis with diffuse KPs is a potential rare complication of intravitreal faricimab and must be considered in patients presenting with new ocular inflammation or IOP elevation while undergoing treatment with faricimab. The intraocular inflammation appears to respond well to discontinuation of faricimab and treatment with local corticosteroids.},
}

@article {pmid41990841,
year = {2026},
author = {Grün, M and Faatz, H},
title = {[Optical coherence tomography angiography].},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2729-1450},
pmid = {41990841},
issn = {1439-3999},
abstract = {Optical coherence tomography angiography (OCTA) has become increasingly established as a diagnostic procedure in clinical practice in recent years. In the field of medical retina in particular, it serves as a useful aid to the morphological assessment of vascular diseases such as neovascular age-related macular degeneration and diabetic retinopathy. Technically speaking, it is a further development of optical coherence tomography (OCT) and therefore offers the advantage of being non-invasive. Even though other imaging modalities still need to be used for certain clinical matters, OCTA offers a suitable alternative to invasive procedures in some situations or can be a helpful supplement in cases of unclear findings. In addition, OCTA has led to a better understanding of the pathophysiology and course of vascular diseases in a scientific context. Recent developments have already reduced or eliminated some of the limitations of OCTA and further improvements for use in clinical practice can be expected in the future.},
}

@article {pmid41990981,
year = {2026},
author = {Keenan, TDL and Hébert, M and Chew, EY and Johnson, MW},
title = {What Should Patients with Age-Related Macular Degeneration Eat?.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.04.003},
pmid = {41990981},
issn = {1879-1891},
abstract = {PURPOSE: To summarize relevant data on what individuals with age-related macular degeneration (AMD) should eat and to propose simple, evidence-based, dietary and micronutrient supplement guidelines that can be shared with patients and physicians.

DESIGN: Focused literature review with interpretation and clinical perspective METHODS: We selectively reviewed literature on the associations between diet, oral micronutrient supplementation, and AMD progression, synthesizing evidence by disease stage. Sources included the Age-Related Eye Disease Studies (AREDS/AREDS2) in the United States, and major epidemiologic and cohort studies in Europe and North America.

RESULTS: Across disease stages, closer adherence to a Mediterranean diet is consistently associated with substantially slower AMD progression. In AREDS, individuals with early AMD who adhered more closely to a Mediterranean diet were significantly less likely to develop intermediate AMD. In AREDS/AREDS2 participants with intermediate AMD, higher Mediterranean diet adherence was strongly associated with decreased risk of progression to late AMD, especially for geographic atrophy (GA). Specific dietary components were particularly influential: higher fish intake was most protective, followed by higher vegetable and lower red meat intake. For individuals with geographic atrophy (GA), a Mediterranean diet was associated with markedly slower GA enlargement, including slower expansion towards the fovea. Higher intake of fruit and vegetables, lower intake of red meat, and avoidance of heavy alcohol consumption were most important in the modulation of GA expansion. Oral micronutrient supplementation with the AREDS2 formulation decreased progression to late AMD for individuals with intermediate AMD (or advanced disease in one eye) and slowed expansion of extrafoveal GA towards the fovea. Notably, the benefits of healthy diet and AREDS2 supplementation were found to be complementary and non-redundant.

CONCLUSION: Individuals with AMD should adopt a Mediterranean diet (or similar pattern), which appears beneficial at all disease stages. Dietary emphasis may vary by stage. A predominantly plant-based diet appears preferable to an animal-based diet, particularly for late AMD with GA. The AREDS2 formulation is recommended for individuals with intermediate or advanced AMD, and may be especially helpful for those with extrafoveal GA. A Mediterranean diet and micronutrient supplementation have complementary actions, so should be used together for maximal benefit.},
}

@article {pmid41787550,
year = {2026},
author = {Spero, V and Escher, P and Braga-Lagache, S and Enzmann, V and Zinkernagel, M},
title = {Systemic inflammation triggers local complement production in the mouse retina and RPE.},
journal = {Journal of neuroinflammation},
volume = {23},
number = {1},
pages = {},
pmid = {41787550},
issn = {1742-2094},
abstract = {UNLABELLED: Systemic inflammation is increasingly recognized as a potential contributor in sight threatening retinal diseases such as Age-related Macular Degeneration (AMD). Yet, its impact on local eye immune responses and further pathological processes remains poorly understood. This study aims to elucidate the effect of peripheral immune activation on the local complement system, a central component of innate immunity with a dual role in maintaining ocular homeostasis and mediating inflammation, in the mouse retina and retinal pigment epithelium (RPE). Using a systemic lipopolysaccharide (LPS) challenge and a high-resolution proteomic approach, we observed a significant increase in complement factor 3 (C3) production in the RPE and retina 24 h post-injection. Further analysis confirmed the local source of complement signaling in resident cells such as astrocytes and RPE, independently from blood-retina barrier disruption. These findings reveal a direct cross-talk between systemic immune activation and ocular complement activation, and highlight the potential implications of systemic inflammation in the pathogenesis of ocular diseases, underlining the importance of future research into targeted therapies for inflammation-driven conditions.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-026-03737-y.},
}

@article {pmid41982839,
year = {2025},
author = {Agarwal, K and Sadeghi, E and Mehrotra, K and Bollepalli, SC and Vupparaboina, KK and Chhablani, J},
title = {Uncomplicated Cataract Surgery and Neovascular Conversion of Age-Related Macular Degeneration: Fifteen-Year Follow-Up Study.},
journal = {Journal of current ophthalmology},
volume = {37},
number = {3},
pages = {346-351},
pmid = {41982839},
issn = {2452-2325},
abstract = {PURPOSE: To evaluate the impact of cataract surgery on neovascular age-related macular degeneration (nAMD) conversion over a 15-year follow-up period.

METHODS: This 15-year retrospective study on dry AMD patients compared Group A (cataract surgery) and Group B (no surgery). It assessed nAMD conversion rates, mean logMAR best-corrected visual acuity (BCVA), and final central macular thickness (CMT) changes. Kaplan-Meier survival curves and log-rank tests evaluated the impact of cataract surgery on time to conversion.

RESULTS: This study included 73 eyes from 46 patients, with a mean baseline age of 68.78 ± 8.62 years. Among them, 31 (67.39%) were female. Final analyses comprised 43 eyes in Group A and 30 eyes in Group B. Group A had a higher baseline age (70.3 ± 8.58 vs. 65.6 ± 7.24; P = 0.01), but baseline BCVA was similar (0.26 ± 0.33 vs. 0.29 ± 0.40; P = 0.61). The nAMD conversion rate showed no difference (32.55% vs. 36.66%; P = 0.491), as well as mean age at conversion (77.5 ± 8.10 vs. 77 ± 3.66; P = 0.80). The mean interval of conversion from cataract surgery was 5.24 ± 3.22 years. Final logMAR BCVA (0.78 ± 0.73 vs. 0.8 ± 0.76; P = 0.61) and mean CMT at final follow-up (167.6 ± 77.26 vs. 187 ± 85.19; P = 0.90) were also similar. The log-rank test showed no association between cataract surgery and conversion rate (P = 0.789).

CONCLUSIONS: The present study did not find a significant difference in conversion from dry to wet AMD between patients who underwent cataract surgery and who did not. No significant difference was noted in the age at the time of conversion between the two groups.},
}

@article {pmid41984164,
year = {2026},
author = {Mauschitz, MM and Goerdt, L and Helbig, H and Holz, FG and Finger, RP and Brandl, C},
title = {Nutrition and dietary supplements in age-related macular degeneration.},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41984164},
issn = {2731-7218},
abstract = {BACKGROUND: Nutrition has an influence on the condition of our retina and appears to play a role in the complex, multifactorial pathogenesis of age-related macular degeneration (AMD).

OBJECTIVES: This article summarizes the current epidemiological evidence on nutrition and AMD and discusses the intake of specific nutrients as well as nutritional supplements and their potential role in prevention and disease modification.

MATERIAL AND METHODS: A narrative literature review of epidemiological studies, clinical trials and experimental work on the role of individual micronutrients, supplements and dietary patterns in AMD was carried out.

RESULTS: There is evidence of a protective effect for individual nutrients such as lutein, zeaxanthin, zinc and omega‑3 fatty acids. The AREDS studies in particular show a reduction in the progression of intermediate AMD to late stages through defined supplements. In addition, a Mediterranean diet correlates with a reduced risk of AMD. Nevertheless, the study results remain contradictory in some cases, which is due to methodological limitations and the complex pathogenesis of AMD.

DISCUSSION: Nutrition can potentially influence and reduce the risk for and progression of AMD. The existing literature underlines the potential of nutrition-based approaches, which must be further investigated in the future.},
}

@article {pmid41984830,
year = {2026},
author = {Brillante, S and Volpe, M and Diana, A and Negueruela, S and Molinari, M and Saurino, R and Cipollaro, E and Polishchuk, E and Tenderini, E and Damiano, C and Tornabene, P and Polishchuk, R and Parenti, G and Tarallo, A and Banfi, S and Trapani, I and Carrella, S and Indrieri, A},
title = {Uncovering mitochondrial defects in photoreceptors opens therapeutic opportunities for Stargardt disease.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {16},
pages = {e2504764123},
doi = {10.1073/pnas.2504764123},
pmid = {41984830},
issn = {1091-6490},
support = {M2020184//BrightFocus Foundation (BFF)/ ; PRIN2020 grant 2020XBCMHJ//Ministero dell'Università e della Ricerca (MUR)/ ; TGM22MT01//Fondazione Telethon (FT)/ ; },
mesh = {Animals ; *Stargardt Disease/genetics/therapy/pathology/metabolism ; MicroRNAs/genetics/metabolism ; *Mitochondria/metabolism/pathology/genetics ; Mice ; Humans ; Retinal Pigment Epithelium/metabolism/pathology ; ATP-Binding Cassette Transporters/genetics/metabolism ; *Macular Degeneration/congenital/genetics/pathology/therapy/metabolism ; GTP Phosphohydrolases/metabolism/genetics ; Mice, Knockout ; Disease Models, Animal ; Organoids/metabolism/pathology ; *Photoreceptor Cells, Vertebrate/metabolism/pathology ; },
abstract = {Stargardt disease type 1 (STGD1) is the most common hereditary macular degeneration. It is caused by mutations in ABCA4, which result in the progressive degeneration of the retinal pigment epithelium (RPE), ultimately leading to photoreceptor loss. Despite extensive efforts, STGD1 currently lacks effective treatments. Here, we first identified mitochondrial defects in the photoreceptors of Abca4[-/-] mice and STGD1 patient-derived retinal organoids. Specifically, we found reduced mitochondrial content, defective cristae morphology, and downregulation of OPA1, a critical regulator of mitochondrial integrity, demonstrating that photoreceptor defects in STGD1 also have a cell-autonomous origin, besides the RPE dysfunction. Importantly, we also demonstrated that correcting this pathological phenotype through the modulation of microRNAs 181a and b (miR-181a/b), key regulators of mitochondrial function, ameliorates the STGD1 phenotype. Indeed, genetic inactivation and adeno-associated viral vector-mediated silencing of miR-181a/b in STGD1 models restored OPA1 levels, improved mitochondrial phenotype, and reduced lipofuscin accumulation in the RPE. Our study demonstrates that mitochondrial dysfunction in photoreceptors is an important contributor to STGD1 pathology, opening promising therapeutic avenues for this disorder.},
}

Animals
*Stargardt Disease/genetics/therapy/pathology/metabolism
MicroRNAs/genetics/metabolism
*Mitochondria/metabolism/pathology/genetics
Mice
Humans
Retinal Pigment Epithelium/metabolism/pathology
ATP-Binding Cassette Transporters/genetics/metabolism
*Macular Degeneration/congenital/genetics/pathology/therapy/metabolism
GTP Phosphohydrolases/metabolism/genetics
Mice, Knockout
Disease Models, Animal
Organoids/metabolism/pathology
*Photoreceptor Cells, Vertebrate/metabolism/pathology

@article {pmid41985834,
year = {2026},
author = {Chen, KY and Chan, HC and Hwang, YS and Lin, WW and Chan, CM},
title = {Are Müller Glial Cells Gatekeepers of Neuroprotection and Regeneration in Age-Related Macular Degeneration? Unraveling Their Roles in Pathophysiology and Therapeutic Innovation.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101471},
doi = {10.1016/j.preteyeres.2026.101471},
pmid = {41985834},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) is traditionally conceptualized as a disorder of the retinal pigment epithelium (RPE)-photoreceptor axis; however, this paradigm incompletely explains early disease dynamics and therapeutic failure in geographic atrophy (GA). This review aims to redefine AMD progression through a Müller glial cell-centered framework that integrates cellular homeostasis, structural transitions, and stage-dependent therapeutic implications. Emerging transcriptomic, histologic, and functional evidence demonstrates that Müller glial cells actively participate in AMD pathobiology, including complement regulation, metabolic coupling, redox control, and inflammatory signaling. In early AMD, Müller glial cells exhibit adaptive responses that preserve retinal integrity despite increasing metabolic and extracellular stress. Progressive accumulation of basal laminar deposits and extracellular remodeling imposes diffusion constraints and inflammatory burden, promoting glial reprogramming. A critical transition occurs at external limiting membrane (ELM) descent, which corresponds to loss of photoreceptor support, disruption of retinal compartmentalization, and onset of irreversible degeneration. Beyond this threshold, Müller glial cells undergo structural remodeling and contribute to formation of subretinal glial membranes, reflecting a shift from homeostatic support to containment. This framework proposes a biologically testable staging axis from preserved Müller glial cell function to progressive dysfunction, aligning disease progression with therapeutic windows. Pre-ELM stages are characterized by retained plasticity and suitability for neuroprotective and metabolic interventions, whereas post-ELM stages require strategies focused on stabilization and limiting degeneration. Importantly, current clinical trials do not incorporate Müller glial cell state or ELM integrity as stratification variables, contributing to outcome insensitivity. In conclusion, Müller glial cells function as central regulators of retinal homeostasis and disease progression in AMD. Integrating glial biology with structural biomarkers may enable stage-specific precision therapies and improve clinical trial design.},
}

@article {pmid41986091,
year = {2026},
author = {Lee, JH and Bae, K and Lee, EK and Yoon, CK and Park, KH and Park, UC},
title = {Effect of intraocular pressure-lowering agents in highly myopic eyes.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327484},
pmid = {41986091},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: To evaluate the effects of intraocular pressure (IOP)-lowering agents in highly myopic eyes.

METHODS: Highly myopic patients with axial length (AL) data for longer than 5 years were included. The changes in IOP, AL and myopic macular complications during the study period were compared between the eyes treated with IOP-lowering agents (treatment group) and those never treated (control group).

RESULTS: The treatment (30 eyes of 30 patients) and control (90 eyes of 90 patients) groups had comparable baseline characteristics except for IOP, which was significantly higher in the treatment group (p=0.020). During the study period, the treatment group showed a greater mean percentage decrease in IOP per year compared with the control group (-2.13±2.51% /year vs+0.30 ± 2.31% /year; p<0.001). The mean change in AL per year was +0.032 ± 0.050 mm/year in the treatment group and +0.058 ± 0.054 mm/year in the control group (p=0.022), and the difference was more pronounced in eyes with posterior staphyloma or without dome-shaped macula. The progression of myopic macular degeneration (MMD), myopic retinoschisis and myopic choroidal neovascularisation during the study period was comparable between groups, but the increase in MMD category was significantly less frequent in the treatment group (3.3% vs 20.0%; p=0.040). In the multivariate analysis, use of IOP-lowering agents was associated with both decreased axial elongation and lower likelihood of MMD category increase.

CONCLUSION: IOP-lowering agents may be effective in alleviating axial elongation and progression of myopic maculopathy in highly myopic eyes.},
}

@article {pmid41975624,
year = {2026},
author = {Miranda, M and Gupta, P and Sukkar, B and Cantó Catalá, A and Hosseinzadeh, Z},
title = {Müller glial cells for regeneration, retinal organoids, cell transplantation, and neuroprotection.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01256},
pmid = {41975624},
issn = {1673-5374},
abstract = {Müller glial cells are essential for retinal structure and homeostasis and increasingly recognized as dual regulators of retinal degeneration and regeneration. Beyond providing metabolic and structural support, Müller glial cells actively shape disease progression while retaining latent regenerative potential. Growing evidence highlights their roles in retinal degeneration, development, and neuroprotection, particularly in age-related macular degeneration, diabetic retinopathy, and inherited retinal disorders. This review integrates recent advances across five key areas: (1) Müller glial cell dysfunction in retinal disease pathology, including gliosis, inflammatory signaling, and vascular dysregulation; (2) their regenerative capacity, with a critical appraisal of efforts to reprogram Müller glial cells into retinal progenitors in mammalian models and the ongoing controversy surrounding functional neuronal replacement; (3) their contribution to the maturation of induced pluripotent stem cells-derived retinal organoids; (4) their neuroprotective roles through antioxidant, immunomodulatory, and trophic mechanisms; and (5) their emerging applications in cell-based therapies. By highlighting unresolved knowledge gaps-particularly the molecular barriers limiting Müller glial cell reprogramming and the signals governing their switch between protective and pathogenic states, this review positions Müller glial cells as central targets for future retinal regenerative and therapeutic strategies.},
}

@article {pmid41976951,
year = {2026},
author = {Ciszewska, K and Winiarczyk, M and Winiarczyk, D and Mackiewicz, J},
title = {Microperimetry-Based Fixation Training in Patients with Age-Related Macular Degeneration (AMD).},
journal = {Journal of clinical medicine},
volume = {15},
number = {7},
pages = {},
pmid = {41976951},
issn = {2077-0383},
abstract = {Background: Age-related macular degeneration (AMD) is the primary cause of severe visual acuity loss in individuals over 60 with increasing prevalence. Currently, no effective treatments exist for geographic atrophy and macular scarring, highlighting the need for visual rehabilitation in these patients. Microperimetry offers functional assessment at any AMD stage and employs fixation training to help patients utilize the most effective retinal areas for vision. Methods: A prospective study involving 25 patients (50 eyes) aged 67 to 90. The MAIA II microperimeter assessed scotoma size and location, retinal sensitivity, macular integrity, fixation parameters (P1, P2, 63%BCEA, 95%BCEA), fixation stability, and preferred retinal locus. Quality of life was evaluated using the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). A subgroup with inactive AMD-related macular changes, either bilateral geographic atrophy (13 patients, 26 eyes) or bilateral scarring (12 patients, 24 eyes), was identified, all exhibiting bilateral absolute central scotomas of at least 2 degrees. Each patient completed 10 fixation training sessions with a microperimeter, training the eye with better acuity weekly. One-week post-training, a functional assessment was performed on both trained and untrained eyes. Results: Fixation training significantly improved best corrected visual acuity (BCVA) in trained eyes (mean change -0.14 logMAR, p < 0.001, large effect size) and also in fellow untrained eyes (-0.16 logMAR, p < 0.001). BNVA improved from 2.25 to 1.86 in trained eyes (p < 0.001) and from 2.96 to 2.76 in untrained eyes (p = 0.004). Fixation stability parameters improved significantly, including increases in P1 and P2 and reductions in Bivariate Contour Ellipse Area (BCEA). Quality of life measured using the NEI-VFQ-25 questionnaire improved significantly in 9 of 11 domains. Conclusions: Microperimetry may be a valuable tool for assessing visual function in AMD patients. Fixation training with the MAIA II microperimeter is both safe and effective for vision rehabilitation in those with geographic atrophy and macular scarring.},
}

@article {pmid41977310,
year = {2026},
author = {Yang, JY and Choi, JS and Park, TK},
title = {AAV2.7m8-Mediated MicroRNA Expression Suppresses VEGF-Induced Angiogenic Responses in HUVEC.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
doi = {10.3390/ijms27073123},
pmid = {41977310},
issn = {1422-0067},
support = {RS-2025-02217948//National Research Foundation of Korea/ ; RS-2024-00452984//National Research Foundation of Korea/ ; },
mesh = {Humans ; *MicroRNAs/genetics/metabolism ; *Human Umbilical Vein Endothelial Cells/metabolism ; *Vascular Endothelial Growth Factor A/metabolism/pharmacology/genetics ; *Dependovirus/genetics ; Cell Proliferation ; Cell Movement/genetics ; Genetic Vectors/genetics ; *Neovascularization, Physiologic/genetics ; *Neovascularization, Pathologic/genetics/metabolism ; Signal Transduction ; },
abstract = {Vascular endothelial growth factor (VEGF)-driven pathological angiogenesis constitutes a primary driver of neovascular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic retinopathy (DR). Although anti-VEGF agents demonstrate clinical efficacy, their limited intraocular half-life mandates repeated intravitreal injections, thereby highlighting the imperative for long-term therapeutic strategies. In the present study, we assessed the anti-angiogenic potential of retinal organoid-derived microRNAs (miRNA) delivered via an engineered adeno-associated virus vector. Human umbilical vein endothelial cells (HUVEC) were transduced with AAV2.7m8 vectors to overexpress three candidate miRNA (miR-26a, miR-122, and let-7a), followed by VEGF stimulation to evaluate downstream signaling pathways and angiogenic responses. AAV2.7m8-mediated transduction of HUVEC demonstrated high efficiency without inducing detectable cytotoxicity. Overexpression of these miRNA markedly attenuated VEGF-induced phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK. Functional assays demonstrated suppression of endothelial cell proliferation and cell cycle progression, with miR-122-5p additionally inhibiting migration. All three miRNA substantially inhibited capillary-like tube formation. In aggregate, these results affirm that AAV2.7m8-mediated delivery of retinal organoid-derived miRNA -namely miR-26a-5p, miR-122-5p, and let-7a-5p-markedly suppresses VEGF-induced angiogenic signaling cascades and endothelial cell activation in vitro, thereby establishing their viability as a sustained therapeutic approach for pathological retinal neovascularization.},
}

Humans
*MicroRNAs/genetics/metabolism
*Human Umbilical Vein Endothelial Cells/metabolism
*Vascular Endothelial Growth Factor A/metabolism/pharmacology/genetics
*Dependovirus/genetics
Cell Proliferation
Cell Movement/genetics
Genetic Vectors/genetics
*Neovascularization, Physiologic/genetics
*Neovascularization, Pathologic/genetics/metabolism
Signal Transduction

@article {pmid41977482,
year = {2026},
author = {Phillips, R},
title = {Nutrition, Cell Signalling, Mitochondrial Function, and Chronic Non-Communicable Disease.},
journal = {International journal of molecular sciences},
volume = {27},
number = {7},
pages = {},
doi = {10.3390/ijms27073303},
pmid = {41977482},
issn = {1422-0067},
mesh = {Humans ; *Mitochondria/metabolism ; *Signal Transduction ; Animals ; *Noncommunicable Diseases ; Chronic Disease ; Homeostasis ; Energy Metabolism ; },
abstract = {Cellular homeostasis is a dynamic process which balances anabolic processes with catabolic and recycling processes. These processes require nutrients, which are converted to energy to fuel the complex interactions of intracellular signalling. Cellular health requires that, on average, energy input and energy requirements are matched. Cells contain a nutrient-sensing mechanism which controls the balance between anabolism and catabolism. Normal intracellular functions generate products which regulate signalling pathways, and health at a cellular level requires a fluctuation between relative nutrient abundance and relative nutrient scarcity. This allows clearance of damaged intracellular molecules and organelles. When nutrient supply exceeds cellular requirements, adaptations to intracellular signalling occur, resulting in energy being stored as glycogen in muscle and the liver and fatty acids in adipose tissue. Overfuelling and aberrant fuelling of mitochondria result in oxidative stress, which not only disrupts cellular homeostasis but can alter epigenetic expression, with intergenerational effects. If the recycling mechanisms of the cell are insufficient to clear metabolic products, apoptosis may result or expression of Damage-Associated Molecular Patterns (DAMPs) on the cell surface may occur, activating immunity and inflammation at a systemic level. Disrupted cellular signalling affects cells with different "professional" functions in different organs, and it is the mechanism which underlies the associations between chronic non-communicable diseases such as cancer, type 2 diabetes, cardiovascular disease, neurodegenerative disease, autoimmune diseases, and macular degeneration. Mitochondria are the controllers of energy production and are pivotal in cell signalling. Mitochondrial function governs health at cellular and organismal levels. This paper reviews the influence of nutrition on mitochondrial function, nutrient sensing, autophagy, insulin signalling, and apoptosis-the key pathways in cellular homeostasis.},
}

Humans
*Mitochondria/metabolism
*Signal Transduction
Animals
*Noncommunicable Diseases
Chronic Disease
Homeostasis
Energy Metabolism

@article {pmid41979251,
year = {2026},
author = {Zhao, Z and Ou, Q and Zhu, J and He, Z and Yang, Y and Jiang, J and Wang, Q and Zhou, Y and Liu, Y and Zhu, X and Cui, T and Liu, Y and Xu, J and Gao, F and Jin, C and Wang, J and Lu, L and Bi, Y and Xu, GT and Xu, JY and Tian, H},
title = {Modulation of Iron-Induced Glucose Metabolic Reprogramming Alleviates Retinal Pigment Epithelial Cell Senescence.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {30},
doi = {10.1167/iovs.67.4.30},
pmid = {41979251},
issn = {1552-5783},
mesh = {Animals ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Cellular Senescence/drug effects/physiology ; Mice ; *Glucose/metabolism ; Reactive Oxygen Species/metabolism ; Humans ; Blotting, Western ; Mitochondria/metabolism ; Mice, Inbred C57BL ; Ferric Compounds/toxicity/pharmacology ; Cells, Cultured ; Induced Pluripotent Stem Cells/metabolism ; Electroretinography ; Disease Models, Animal ; Quaternary Ammonium Compounds/toxicity ; Metabolic Reprogramming ; },
abstract = {PURPOSE: This study aimed to investigate whether iron overload induces retinal pigment epithelial (RPE) cell senescence through glucose metabolic reprogramming and to evaluate the therapeutic potential of targeting this metabolic pathway.

METHODS: We utilized human-induced pluripotent stem cell-derived RPE cells and induced RPE cells, along with mouse models with intravitreal or intraperitoneal injection of ferric ammonium citrate (FAC), to evaluate the effect of iron overload on RPE senescence. Proteomics, targeted metabolomics, reactive oxygen species (ROS) assay kits, JC-1 assay kit, reverse-transcription polymerase chain reaction, SA-β-gal staining, and western blot were used to assess mitochondrial function, ROS, and senescence markers. 2-Deoxy-d-glucose (2-DG), pyruvate kinase M2 inhibitor-1 (PKM2-IN-1), and sodium oxamate (SO) were used to modulate glucose metabolism flux. Flash electroretinography recording was used to assess visual function.

RESULTS: Iron overload triggered significant glucose metabolic reprogramming in RPE cells, characterized by a time-dependent metabolic shift. Early exposure to FAC induced a transient surge in glucose metabolic flux, which elevated mitochondrial ROS production and disrupted mitochondrial homeostasis, ultimately leading to cellular senescence. Importantly, early inhibition of this metabolic surge with 2-DG or PKM2-IN-1 effectively attenuated senescence by reducing ROS levels and preserving mitochondrial function. Conversely, enhancing pyruvate flux with SO exacerbated senescence. The protective effect of 2-DG against iron-induced RPE senescence was further confirmed in a mouse model, where it preserved visual function and reduced senescence markers.

CONCLUSIONS: Glucose metabolic reprogramming mediates iron-induced RPE senescence, with transient glucose flux surge driving pathology via ROS-related mitochondrial damage. Targeting glucose metabolism may preserve mitochondria homeostasis and prevent RPE degeneration in age-related macular degeneration.},
}

Animals
*Retinal Pigment Epithelium/metabolism/drug effects/pathology
*Cellular Senescence/drug effects/physiology
Mice
*Glucose/metabolism
Reactive Oxygen Species/metabolism
Humans
Blotting, Western
Mitochondria/metabolism
Mice, Inbred C57BL
Ferric Compounds/toxicity/pharmacology
Cells, Cultured
Induced Pluripotent Stem Cells/metabolism
Electroretinography
Disease Models, Animal
Quaternary Ammonium Compounds/toxicity
Metabolic Reprogramming

@article {pmid41979253,
year = {2026},
author = {Foshe, S and Anderson, BD and Song, Y and Shi, S and Lee, S and Bell, BA and Park, HG and Brenna, JT and Shchepinov, M and Dunaief, JL},
title = {Oral Deuterated Docosahexaenoic Acid Protects Against Onset and Progression of RPE Degeneration in a Mouse Model of Chronic Oxidative Stress.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {28},
doi = {10.1167/iovs.67.4.28},
pmid = {41979253},
issn = {1552-5783},
mesh = {Animals ; *Oxidative Stress/drug effects ; *Docosahexaenoic Acids/administration & dosage ; *Retinal Pigment Epithelium/pathology/drug effects/metabolism/ultrastructure ; Mice ; Disease Models, Animal ; Mice, Knockout ; Tomography, Optical Coherence ; Disease Progression ; Mice, Inbred C57BL ; Administration, Oral ; Electroretinography ; Female ; *Macular Degeneration/prevention & control ; Ophthalmoscopy ; Hepcidins/genetics ; },
abstract = {PURPOSE: Oxidative stress is associated with many retinal diseases, including age-related macular degeneration (AMD). The purpose of this study is to investigate the efficacy of oral deuterated docosahexaenoic acid (D-DHA), an oxidation-resistant lipid, in a mouse model with features of dry AMD. We also evaluated whether long-term D-DHA dosing affects normal retinal structure or function.

METHODS: Liver-specific hepcidin (Hepc) and ceruloplasmin/hepcidin (Cp/Hepc) knock-out (KO) mice were fed experimental diet containing 0.25% D-DHA or control containing normal H-DHA during various stages of disease progression. Retinal pigment epithelium (RPE) damage was assessed with in vivo scanning laser ophthalmoscopy (SLO) imaging and histology. For the safety study, wild-type mice were fed the diets beginning in utero or at 3 months of age, continuing for 12 months. These mice were analyzed to assess retinal structure (SLO, optical coherence tomography [OCT], and transmission electron microscopy [TEM]), function (ERG), and gene expression (qPCR).

RESULTS: KO mice fed control diet developed expanding autofluorescent patches of hypertrophic RPE cells. This damage was markedly prevented or halted by diet with D-DHA, depending on age at diet onset. Wild-type mice administered diet with D-DHA from age 3 to 15 months had no retinal abnormalities. Mice administered D-DHA beginning in utero had normal retinal development and structure but minor deficits in ERG amplitudes and Rpe65 expression by age 12 months.

CONCLUSIONS: Oral D-DHA was strongly protective against RPE ferroptosis, with minimal side effects. This study suggests that DHA oxidation is a key mechanism of retinal iron toxicity and supports the potential clinical application of D-DHA for diseases involving retinal oxidative stress.},
}

Animals
*Oxidative Stress/drug effects
*Docosahexaenoic Acids/administration & dosage
*Retinal Pigment Epithelium/pathology/drug effects/metabolism/ultrastructure
Mice
Disease Models, Animal
Mice, Knockout
Tomography, Optical Coherence
Disease Progression
Mice, Inbred C57BL
Administration, Oral
Electroretinography
Female
*Macular Degeneration/prevention & control
Ophthalmoscopy
Hepcidins/genetics

@article {pmid41979423,
year = {2026},
author = {Jiang, H and Wang, X and Wang, L and Fan, Y and Li, Z and Ma, M and Liu, S and Li, B and Shi, J and Li, C and Ma, L and Li, J and Zhang, W},
title = {Association of dietary calcium and its food sources with age-related macular degeneration in China: a population-based case-control study.},
journal = {Food & function},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5fo04327a},
pmid = {41979423},
issn = {2042-650X},
abstract = {Background & aims: Recent studies, primarily in developed countries, suggest that higher dietary calcium intake is associated with lower odds of age-related macular degeneration (AMD). However, evidence on this association is lacking in China, where the population has unique dietary patterns and relatively low calcium intake. The aim of this study was to investigate the association of dietary calcium and its major sources with the likelihood of AMD in a Chinese population. Methods: A case-control study was performed within the frame of the Xi'an Eye Study. A total of 284 AMD cases and 284 matched controls who completed the eye examination and a detailed semi-quantitative food frequency questionnaire were included in the present analysis. Multivariable-adjusted conditional logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of dietary calcium and its main sources. Results: In the multivariable adjusted model, an increasing amount of dietary calcium intake was associated with significantly lower odds of AMD, especially among participants with a dietary calcium intake of less than 800 mg per 2000 kcal per day. The OR for the comparison of the top with the bottom tertile of dietary calcium intake was 0.46 (95%CI: 0.23, 0.90; P-trend = 0.02). Regarding major sources of calcium, a significant inverse association was only observed for dairy-based calcium intake, with an OR of 0.45 (95%CI: 0.23, 0.89; P-trend = 0.02). Consumption of dairy products, particularly milk (OR: 0.45 from a comparison of ≥4 servings per week with never/rarely; 95%CI: 0.22, 0.90; P-trend = 0.05) and yogurt (OR: 0.38 from a comparison of ≥2 servings per week with never/rarely; 95%CI: 0.19, 0.78; P-trend = 0.01), was also associated with lower odds of AMD. No significant associations were found for milk powder or dietary intake of calcium from vegetables or legumes. Conclusions: Higher intake of calcium and its major food sources, such as milk and yogurt, was associated with a significantly decreased likelihood of AMD in a Chinese population with relatively low dietary calcium intake. These findings align with current public health recommendations for maintaining adequate calcium status and emphasize that the health implications of calcium may depend on its dietary sources.},
}