@article {pmid42722145,
year = {2026},
author = {Seol, A and Jeong, JS and Kim, JE and Song, HJ and Lim, SJ and Wang, SH and Ryu, YE and Kim, YR and Yun, W and An, BS and Hwang, DY},
title = {HepG2 cells-derived exosomes exacerbate blue light-induced AMD-like retinal degeneration in A2E-laden ARPE-19 cells and BALB/c mice.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111231},
doi = {10.1016/j.exer.2026.111231},
pmid = {42722145},
issn = {1096-0007},
abstract = {Exosomes derived from hepatic cells have emerged as important mediators of inter-organ communication and may contribute to retinal degeneration associated with age-related macular degeneration (AMD) through the liver-eye axis. However, their role in AMD pathogenesis remains poorly understood. In this study, we investigated whether HepG2 cell-derived exosomes (HG-EX) exacerbate AMD-like retinal degeneration using in vitro and in vivo AMD-mimicking models. ARPE-19 cells co-treated with N-retinylidene-N-retinylethanolamine (A2E) and blue light (BL), as well as BL-exposed BALB/c mice, were pretreated with HG-EX. In AMD-mimicking ARPE-19 cells, HG-EX pretreatment significantly increased intracellular reactive oxygen species (ROS) and nitric oxide (NO) production while suppressing the expression of superoxide dismutase (SOD) and nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, HG-EX altered inflammatory signaling by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, while enhancing inflammasome-related protein expression. Apoptosis-related proteins and pro-angiogenic factors were also markedly elevated following HG-EX treatment. In AMD-mimicking mice, HG-EX administration significantly increased the retinal expression of COX-2, B-cell lymphoma 2 (Bcl-2)/ Bcl-2-associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, accompanied by a reduction in the thickness of the outer segment (OS) and inner nuclear layer (INL). Collectively, these findings demonstrate that HG-EX exacerbate oxidative stress, inflammation, apoptosis, and angiogenesis in both cellular and animal models that recapitulate selected pathological features of AMD. Our results suggest that HG-EX may contribute to AMD-like retinal degeneration and warrant further investigation into their potential role in AMD pathogenesis.},
}

@article {pmid42720425,
year = {2026},
author = {Hua, X and Hormel, TT and Wang, J and Flaxel, CJ and Bailey, ST and Hwang, TS and Jia, Y},
title = {Structural and Angiographic Assessment of the Nerve Fiber Layer in Age-Related Macular Degeneration and Diabetic Retinopathy.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {11},
pages = {17},
doi = {10.1167/iovs.67.11.17},
pmid = {42720425},
issn = {1552-5783},
mesh = {Humans ; Female ; *Diabetic Retinopathy/diagnosis/pathology ; *Nerve Fibers/pathology ; Male ; Aged ; *Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/pathology ; *Retinal Ganglion Cells/pathology ; Tomography, Optical Coherence/methods ; Middle Aged ; *Retinal Vessels/pathology ; Aged, 80 and over ; *Optic Disk/pathology/blood supply ; },
abstract = {PURPOSE: The purpose of this study was to evaluate structural and microvascular alterations in the nerve fiber layer (NFL) in age-related macular degeneration (AMD) and diabetic retinopathy (DR).

METHODS: A total of 74 healthy controls, 101 patients with AMD, and 117 patients with DR were included. One eye per participant was imaged using a Solix OCTA device centered on the optic disc to measure NFL thickness and nerve fiber layer plexus (NFLP) vessel density (VD). For both parameters, we analyzed the independent associations of age, AMD, and DR; compared age-matched healthy controls with the AMD groups and with the DR groups; and evaluated correlations with age in healthy controls.

RESULTS: Multivariate analyses demonstrated that age was independently associated with both NFL thickness and NFLP VD, whereas AMD was not associated with either parameter and DR was associated only with NFLP VD. The associations of AMD and DR with these two parameters were also confirmed in age-matched analyses. Additionally, NFLP VD decreased significantly with increasing DR severity (P < 0.001). In healthy controls, age was significantly correlated with both NFL thickness (Spearman's ρ = -0.26, P = 0.026) and NFLP VD (ρ = -0.32, P = 0.006).

CONCLUSIONS: NFL thickness was associated with age, but not with AMD or DR. In contrast, DR was independently associated with reduced NFLP VD, which also significantly correlated with DR severity. These findings provide evidence supporting further investigation of NFLP VD in relation to DR, while accounting for age.},
}

Humans
Female
*Diabetic Retinopathy/diagnosis/pathology
*Nerve Fibers/pathology
Male
Aged
*Fluorescein Angiography/methods
*Macular Degeneration/diagnosis/pathology
*Retinal Ganglion Cells/pathology
Tomography, Optical Coherence/methods
Middle Aged
*Retinal Vessels/pathology
Aged, 80 and over
*Optic Disk/pathology/blood supply

@article {pmid42721102,
year = {2026},
author = {Lenhof, S and Mathis, T and Lepretre, N and Rencker, J and Kodjikian, L},
title = {Faricimab in previously treated nAMD: Real-World Outcomes of a No-Loading-Dose Switching Protocol.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1},
doi = {10.1159/oph/aeeag012},
pmid = {42721102},
issn = {1423-0267},
abstract = {INTRODUCTION: Evaluate efficacy, anatomical outcomes, and safety of switching to faricimab without a loading dose, using a standardized institutional switch protocol, in patients with previously treated neovascular age-related macular degeneration (nAMD) who achieved a maximum fluid-free interval of 8 weeks or less with aflibercept or ranibizumab.

METHODS: Retrospective, single-center cohort study conducted at Croix-Rousse Hospital, Lyon and included eyes with a maximum fluid-free interval of 8 weeks or less on aflibercept or ranibizumab, switched to faricimab between November 2023 and December 2024. Eyes were classified as Poor Responders (PR) or Frequent Flyers (FF) based on their prior anti-VEGF response. No loading dose was administered. Primary outcome was change in last intended treatment interval. Secondary outcomes included best-corrected visual acuity (BCVA), SD-OCT parameters, predictors of interval extension and safety.

RESULTS: 128 eyes were included. Before switching, mean (SD) treatment duration was 36.4 (21.9) months with a mean (SD) 28.2 (17.0) intravitreal injections. After switching, the median gain in the last intended interval was 2.7 [IQR 2.1-3.3] weeks (p<0.001). Subgroup analysis showed a median gain of 3.1 weeks in PR (p<0.001) and 2.4 weeks in FF (p<0.001). BCVA remains stable (p=0.37). Significant reductions were observed in CMT (p<0.001), SHRM (p=0.02), IRF (p<0.001), and SRF (p<0.001). Baseline characteristics were not associated with treatment interval extension. There was one case of anterior uveitis and vitritis, which resolved with topical corticosteroid treatment.

CONCLUSION: In previously treated nAMD patients, switching to faricimab without a loading dose achieved meaningful treatment interval extension, potentially reducing treatment burden without compromising efficacy.},
}

@article {pmid42717802,
year = {2026},
author = {Freeman, WR and Vail, D and Ye, M and López, FJ and Robinson, MR and Huang, J and Hallak, JA},
title = {Real-World Dosing Intervals for Long-Acting Anti-VEGF Intravitreal Injection Therapies in nAMD and DME: Academy IRIS[®] Registry Analysis.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683261484815},
doi = {10.1177/10807683261484815},
pmid = {42717802},
issn = {1557-7732},
abstract = {PURPOSE: To determine real-world dosing intervals for long-acting intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

METHODS: Retrospective observational cohort study in American Academy of Ophthalmology IRIS[®] Registry (Intelligent Research in Sight) patients with nAMD or DME treated with aflibercept 8 mg (aflibercept) or faricimab. Mean injection intervals during a ≤24-month period beginning 3 or 4 months after the initial injection were evaluated and descriptively contrasted with those in phase 3 clinical trials.

RESULTS: The mean dosing interval was 5-8, 9-12, and ≥13 weeks in 27.5%, 45.6%, and 25.8% of aflibercept-treated patients with nAMD (n = 40,065); 27.0%, 43.4%, and 28.3% of aflibercept-treated patients with DME (n = 13,045); 40.5%, 36.1%, and 20.8% of faricimab-treated patients with nAMD (n = 132,697); and 42.2%, 31.7%, and 22.5% of faricimab-treated patients with DME (n = 39,849). Dosing intervals were consistent between treatment-naïve and previously treated patients. In aflibercept phase 3 studies, 77% (nAMD) and 89% (DME) of patients achieved a 16-week dosing interval. In faricimab phase 3 studies, 45% (nAMD) and 52% (DME) of patients achieved a 16-week dosing interval.

CONCLUSION: Extension of injection intervals to 16 weeks is greatly reduced in real-world experience compared with phase 3 clinical studies. This discrepancy could be explained by protocol-mandated restrictive rescue criteria used in the registration studies, allowing injection only after vision loss and significant fluid recurrence. Current longer-acting anti-VEGF medications offer an extension to only 5-12 weeks for most patients in the real world.},
}

@article {pmid42718898,
year = {2026},
author = {Shen, LL and Rosenfeld, PJ and Beqiri, S and O'Brien, RC and Zhang, J and Chew, EY and Del Priore, LV and Stewart, JM},
title = {Intereye Correlation in Bilateral Geographic Atrophy: Morphology and Growth Rates in the Age-Related Eye Disease Study.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101353},
pmid = {42718898},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate intereye correlation in geographic atrophy (GA) lesion morphology, topography, and growth rates, and whether fellow eyes could improve trial efficiency as internal controls.

DESIGN: Secondary analysis of a multicenter, prospective, randomized controlled trial.

PARTICIPANTS: Age-Related Eye Disease Study participants with bilateral GA.

METHODS: Color fundus photographs were used to delineate GA lesions and measure area, perimeter, circularity index, focality, and lesion number. Intereye correlations were evaluated cross-sectionally and longitudinally for 3 GA growth rates (area, square root-transformed, and perimeter-adjusted growth rate). Longitudinal correlations used the first-to-last interval (mean, 5.5 years). Sample-size requirements for paired and unpaired designs were estimated through exploratory power analyses in eyes with 1-year follow-up.

MAIN OUTCOME MEASURES: Geographic atrophy size, morphology, topographic distribution, and growth rate.

RESULTS: In 226 eyes from 113 patients, moderate-to-strong associations were observed between fellow eyes for GA area (ρ = 0.63), perimeter (ρ = 0.69), circularity index (ρ = 0.56), and across all 4 quadrants (range, ρ = 0.51-0.61). Longitudinally, intereye associations were moderate-to-strong for GA area growth rates (ρ = 0.74), square root-transformed area growth rates (ρ = 0.62), and perimeter-adjusted growth rates (ρ = 0.60). These values reflect the first-to-last interval (mean, 5.5 years); over 1 year, correlations were markedly lower (ρ = 0.53, 0.40, 0.34). By baseline lesion size, intereye correlation was slightly higher for area growth rate in small lesions (≤0.9 disc areas [DAs]) but comparable between area- and perimeter-adjusted rates in larger lesions (>0.9 DA). In exploratory 1-year power analyses, a paired design with within-participant randomization of study and fellow eyes was associated with approximately 40% lower estimated sample-size requirements than an unpaired design (149 pairs vs. 250 eyes per arm for area growth rate); adding a perimeter-adjusted endpoint in lesions >0.9 DA reduced the estimate to 50 pairs per arm.

CONCLUSIONS: We observed moderate-to-strong inter-eye correlations in GA morphology, topography, and progression. For exploratory designs of local unilateral therapies, fellow eyes may serve as internal controls alongside square root-transformed or perimeter-adjusted endpoints, reducing sample sizes, particularly for lesions >0.9 DA. Because these analyses use color fundus photography rather than fundus autofluorescence, they are hypothesis-generating for modern trials. These correlations may also inform group-level counseling on fellow-eye progression.

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

@article {pmid42718940,
year = {2026},
author = {Jaffe, GJ and Wykoff, CC and McCaleb, ML and Barrett, TD and Frazer-Abel, A and Norris, D and Luhmann, UFO and Cukras, C and Yin, L and Lomax, M and Fauser, S and Schneider, E and Brice, GT and , },
title = {GOLDEN: Efficacy and Safety of Complement Factor B Antisense, Sefaxersen, in Geographic Atrophy due to Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101340},
pmid = {42718940},
issn = {2666-9145},
abstract = {OBJECTIVE: To evaluate the efficacy and safety of sefaxersen, an investigational antisense oligonucleotide targeting complement factor B (FB), in slowing the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

DESIGN: Randomized, double-masked, placebo-controlled, adaptive phase II clinical trial.

SUBJECTS: A total of 332 patients with GA secondary to AMD were enrolled, with 91% of treated patients completing the final study visit at 56 weeks.

METHODS: In stage 1, 58 patients received subcutaneous injections of 40, 70, or 100 mg sefaxersen or placebo monthly. An interim analysis for FB, pharmacokinetics, and safety was conducted when patients reached at least 13 weeks of treatment to select 2 doses for expansion. In stage 2, an additional 274 patients were randomized to 40 or 70 mg sefaxersen or placebo. Patients were stratified based on baseline GA size, baseline rate of GA growth, and presence/history of exudative choroidal neovascularization in the fellow eye. Geographic atrophy area was assessed by fundus autofluorescence imaging. Safety assessments included ocular and systemic adverse events, laboratory parameters, and vital signs.

MAIN OUTCOME MEASURES: The primary endpoint was the rate of GA lesion growth from baseline to week 49. Prespecified endpoints included changes from baseline in best-corrected visual acuity, low-luminance visual acuity, systemic complement measures, and occurrence of treatment-related adverse events.

RESULTS: Sefaxersen did not significantly reduce the rate of GA growth versus placebo. Differences in adjusted mean GA rate of growth versus placebo were -0.25 mm[2] (-11.5%, P = 0.171) and -0.08 mm[2] (-3.8%, P = 0.647) for 40 and 70 mg groups, respectively. At steady state, a reduction in adjusted mean plasma FB levels (40 mg: -63% and 70 mg: -69%) led also to a reduction in alternative pathway activity (adjusted mean -22% and -34%, respectively). The safety profile, both ocular and nonocular, of sefaxersen was comparable to that of the placebo, with the most common adverse events being coronavirus disease 2019, urinary tract infections, and nasopharyngitis.

CONCLUSIONS: Sefaxersen reduced systemic FB levels and alternative pathway activity, but the effect on GA growth rate was not significant compared with placebo. The treatment was well tolerated with a safety profile consistent with previous studies.

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

@article {pmid42718944,
year = {2026},
author = {de Vries, VA and Lee, SS and Stuart, KV and Schulze, A and Hunter, ML and Hopf, S and Pfeiffer, N and Lingham, G and Luben, RN and Wang, YX and Haarman, AEG and Tedja, MS and Verhoeven, VJM and Jonas, JB and Schuster, AK and Khawaja, AP and Klaver, CCW and Mackey, DA and Ramdas, WD and , },
title = {A Comprehensive Assessment of the Shared Genetic Architecture between Myopia and Open-Angle Glaucoma.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101328},
pmid = {42718944},
issn = {2666-9145},
abstract = {OBJECTIVE: Individuals with high myopia have an increased prevalence of open-angle glaucoma (OAG). We aim to clarify the possibly shared genetic architecture of myopia and OAG, in particular in high myopes with myopic macular degeneration (MMD), where OAG screening is highly challenging.

DESIGN: Individual participant data meta-analysis of one-sample Mendelian randomization analyses and pleiotropic analysis under a composite null hypothesis.

PARTICIPANTS: A total of 34 825 participants from 6 population-based cohort studies and 1 high myopia case-control study, including 708 OAG and 1953 high-myopia cases.

METHODS: First, we calculated and validated genetic risk scores (GRSs) for OAG and myopia in each cohort. We subsequently meta-analyzed linear and logistic regression models for the association of a myopia GRS with OAG, intraocular pressure (IOP), and vertical cup-to-disc ratio (VCDR), and the association of an OAG-GRS with high myopia, axial length, and spherical equivalent. We stratified the analysis of OAG in different stages of axial elongation, and in high myopes with or without MMD. Pleiotropic analysis under a composite null hypothesis was applied to genome-wide association study summary statistics.

MAIN OUTCOME MEASURES: Odds ratio (OR) of OAG and high myopia, and mean difference in IOP, VCDR, axial length, and spherical equivalent.

RESULTS: One standard deviation (SD) increase in myopia GRS was associated with an OR (95% CI) of 1.18 (1.09, 1.28) for OAG, a beta (95% CI) of 0.04 (0.00, 0.08) mmHg in IOP, and of 0.005 (0.003, 0.007) in VCDR. The OAG-GRS was not significantly associated with high myopia compared to emmetropes, but a 1 SD increase was associated with a beta (95% CI) of 0.05 (0.01, 0.08) mm in axial length and of -0.05 (-0.10, -0.00) diopters in spherical equivalent. One SD increase in OAG-GRS had a substantially larger effect on OAG in high myopes with MMD, with an OR (95% CI) of 3.83 (1.89, 7.78) compared to 1.55 (1.24, 1.94) in emmetropes. Finally, we identified 95 independent pleiotropic single-nucleotide polymorphisms (SNPs).

CONCLUSIONS: There is strong evidence for pleiotropy between myopia and OAG. Further research into the biological mechanisms of the identified pleiotropic SNPs is needed. An OAG-GRS might help to clinically estimate OAG risk, in particular in individuals with MMD.

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

@article {pmid42720289,
year = {2026},
author = {Rani, T and Vyas, M and Rachna, and Sai Charan, L and Vijayasimha, M},
title = {Comment on: Light Adjustable Lens Implantation with Cataract Surgery in Eyes with Macular Pathology.},
journal = {Journal of cataract and refractive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.jcrs.0000000000002049},
pmid = {42720289},
issn = {1873-4502},
}

@article {pmid42709274,
year = {2026},
author = {Candan, O and Orman, G and Ünlü, N and Uney, G and Acar, DD and Burcu, A},
title = {Pre- and post-COVID-19 changes in retinal disease patterns in Türkiye: insights from a tertiary hospital.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42709274},
issn = {1573-2630},
mesh = {Humans ; *COVID-19/epidemiology ; Retrospective Studies ; Male ; *Tertiary Care Centers/statistics & numerical data ; Middle Aged ; Prevalence ; Female ; Aged ; *Retinal Diseases/epidemiology/diagnosis ; *SARS-CoV-2 ; Adult ; Aged, 80 and over ; },
abstract = {PURPOSE: To estimate the prevalence of common retinal diseases in Türkiye during 2017-2023 and to characterize age and gender-specific differences.

METHODS: This retrospective, single-center, hospital-based study included 475,865 adults presenting to an ophthalmology outpatient clinic. The study period was divided into pre-pandemic (January 2017-March 2020), acute pandemic (March-June 2020), and post-pandemic (June 2020-July 2023) phases. Patient age, gender, diagnoses, and major complications were recorded. The primary outcomes were defined as changes in the prevalence of common retinal diseases and their complications before and after the pandemic.

RESULTS: Among 475,865 adults, 10,131 (2.13%) were diagnosed with a retinal disease. Age-related macular degeneration was the most prevalent disease, with prevalence increasing from 0.99% in the pre-pandemic period to 1.23% in the post-pandemic period (P < .001). Diabetic retinopathy was the second most common and remained stable across the pandemic periods (0.95% and 0.97%; P = .395). Diabetic macular edema (DME) exhibited a notable increase, particularly among patients aged ≥ 50 years (from 16.68 to 26.72%; P < .001). Retinal vein occlusion (RVO) ranked third, with prevalence rising from 0.17% before the pandemic to 0.25% after (P < .001). The proportion of patients with DME secondary to RVO requiring injection increased from 38.2% in the pre-pandemic period to 43.8% in the post-pandemic period.

CONCLUSION: This large-scale longitudinal study demonstrated significant changes in the epidemiology of several retinal diseases across the pre- and post-pandemic periods in Türkiye. However, the mechanisms underlying these changes remain uncertain and need to be clarified through future multicenter population-based studies.},
}

Humans
*COVID-19/epidemiology
Retrospective Studies
Male
*Tertiary Care Centers/statistics & numerical data
Middle Aged
Prevalence
Female
Aged
*Retinal Diseases/epidemiology/diagnosis
*SARS-CoV-2
Adult
Aged, 80 and over

@article {pmid42709378,
year = {2026},
author = {Yang, X and Zhang, S and Wang, Y and Shi, J and Li, W and Lou, X and Yu, Y and Zhang, J and Sang, A},
title = {LAPTM5 correlates with RPE senescence and subretinal fibrosis through the LAPTM5-WWP2-OPTN mitophagy cascade and cGAS/STING activation in a D-galactose-induced aging model.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42709378},
issn = {2509-2723},
support = {M2024045//Jiangsu Commission of Health/ ; K2024063//Jiangsu Commission of Health/ ; LKM2024040//Jiangsu Commission of Health/ ; MS2025005//Nantong Municipal Commission of Health and Family Planning/ ; 23ZH313//Nantong University/ ; },
abstract = {Retinal pigment epithelium (RPE) senescence acts as a core driver of subretinal fibrosis, a major irreversible pathological feature that exacerbates age-related macular degeneration (AMD). Mitophagy is essential for maintaining RPE homeostasis during aging. However, the upstream molecular mechanisms underlying mitophagy impairment in senescent RPE remain poorly defined. Here, we show that lysosomal-associated transmembrane protein 5 (LAPTM5) is significantly upregulated in human AMD specimens and D-galactose (D-gal)-induced aging mouse model, with its overexpression correlating with transcriptomic signatures of RPE senescence and fibrogenesis. Gain- and loss-of-function assays validate that LAPTM5 acts as an important regulator of RPE senescence and senescence-associated secretory phenotype (SASP) production. Mechanistically, LAPTM5 physically interacts with and promotes the lysosome-dependent degradation of WW domain-containing E3 ubiquitin protein ligase 2 (WWP2), which in turn diminishes optineurin (OPTN) polyubiquitination and ablates OPTN-mediated mitophagy. The resulting mitophagy deficiency is associated with cytoplasmic mitochondrial DNA leakage and sustained cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) innate immune activation, stimulating robust senescence-associated secretory phenotype (SASP) release that promotes RPE epithelial-mesenchymal transition (EMT) and exacerbates subretinal fibrotic scarring. Notably, AAV-mediated RPE-specific Laptm5 knockdown efficiently alleviates subretinal fibrotic lesions in the aged mouse model, while pharmacological STING inhibition with H-151 markedly attenuates EMT progression. Collectively, our findings identify a previously uncharacterized LAPTM5-WWP2-OPTN mitophagy cascade and reveal a new pathogenic circuit linking impaired mitophagy to RPE senescence and age-related retinal fibrosis, offering translational prospects for treating senescence-associated fibrotic diseases.},
}

@article {pmid42709406,
year = {2026},
author = {Macchione, RM and Ottaiano-Poli, PA and Germano-Morrel, CS and Tomishige, KS and Kasahara, N},
title = {Vision-related quality of life in glaucoma and age-related macular degeneration patients from a middle-income country.},
journal = {International health},
volume = {},
number = {},
pages = {},
doi = {10.1093/inthealth/ihag089},
pmid = {42709406},
issn = {1876-3405},
support = {//ARVO/ ; },
abstract = {BACKGROUND: Vision-related quality of life (VRQoL)-vision's impact on one's social, emotional and economic well-being-has not been extensively studied in patients living in middle-income countries. The aim of this study was to compare the VRQoL among age-related macular degeneration (AMD), primary open-angle glaucoma (POAG) and normal subjects in Brazil.

METHODS: This was a case-control, cross-sectional study. Patients with AMD or POAG and normal controls underwent a complete eye examination; all participants answered the Brazilian-Portuguese version of the Visual Function Questionnaire 25 (VFQ-25). Each item was scored and an overall composite score was calculated and compared among groups with an analysis of variance test.

RESULTS: The sample included 60 patients with AMD, 64 with POAG and 60 controls. All groups were matched for age, gender, ethnic distribution and comorbidities. The VFQ-25 total score was lower in both AMD (50.6±20.9) and POAG (61.8±20.4) as compared with controls (89.2±9.1, p<0.001); scores for AMD patients were lower than for POAG patients (p<0.001).

CONCLUSIONS: Brazilian patients with POAG, and especially AMD, presented significantly lower VRQoL scores, underscoring the need to improve the care of patients with visual impairment in Brazil.},
}

@article {pmid42709964,
year = {2026},
author = {Wu, Y and Fu, DJ and Zhou, Y and Wagner, SK and Keane, PA},
title = {Performance, Failures, and Oversight of a Large Language Model Agent for Clinical Data Analysis: Evaluation Study.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e99597},
pmid = {42709964},
issn = {1438-8871},
mesh = {*Large Language Models ; Humans ; *Data Analysis ; },
abstract = {BACKGROUND: Large language model (LLM) agents capable of generating and executing statistical code from natural language may broaden access to clinical data analysis, yet which pipeline stages they perform reliably and which require expert oversight remain poorly defined.

OBJECTIVE: This study aimed to evaluate the performance and systematic failure modes of an LLM agent across 5 stages of a clinical data analysis workflow.

METHODS: The publicly available dataset and R script (R Foundation for Statistical Computing) were drawn from a previously published study of 12-year outcomes in 7802 patients with eyes with neovascular age-related macular degeneration at Moorfields Eye Hospital. Participants were evaluated using an LLM agent (Claude; Anthropic) across 3 interaction modes (Chat, Code, and Cowork). It was asked to perform 3 levels of data analysis practice: prompt A, to generate research questions from raw data only; prompt B, to develop a statistical analysis plan (SAP) from a high-level clinical objective, then execute it; and prompt C, to execute an analysis given an investigator-drafted SAP. Each was replicated 3 times (27 total runs). Qualitative evaluation of research question thematic coverage (prompt A), SAP completeness against a reference checklist (prompt B), and evaluation of execution outputs against validated reference values and of result text and narrative summaries against execution logs (prompts B and C) was conducted.

RESULTS: The agent generated 18 clinically grounded questions spanning 7 domains; Cowork mode uniquely reached 3 thematic areas requiring data-driven methods. All 9 SAPs correctly identified the statistical framework. Kaplan-Meier estimates were near-identical across 17 completed runs. Systematic execution errors emerged: SAP quality did not predict code correctness, and within-mode errors propagated identically across independent repetitions. Result text accurately reflected execution logs in nearly all runs, though unit propagation and an undisclosed postcrash rerun were identified. Of 17 narrative summaries, 8 were fully satisfactory; 2 runs produced clinically meaningful errors.

CONCLUSIONS: LLM agents perform reliably for question generation and SAP drafting but require expert verification of formula composition, cohort boundary logic, and concordance computation before results are reported. Using an ophthalmology dataset as a controlled testbed, this study develops and applies an evaluation framework whose lessons are likely applicable across clinical specialties.},
}

*Large Language Models
Humans
*Data Analysis

@article {pmid42712725,
year = {2026},
author = {Long, N and Si, M and Jiang, Y and Chen, F and Chen, B and Jiang, F and Pan, S and Chu, X and Wu, H},
title = {Bionic vision technologies: progress and perspectives on retinal prostheses and optogenetics for the treatment of advanced retinal degeneration.},
journal = {Frontiers in medical technology},
volume = {8},
number = {},
pages = {1898982},
pmid = {42712725},
issn = {2673-3129},
abstract = {Advanced degenerative retinal diseases [e.g., retinitis pigmentosa (RP) and age-related macular degeneration (AMD)] are characterized by irreversible photoreceptor loss, and conventional interventions rarely prevent progression to profound vision loss at advanced stages. Retinal prostheses and optogenetic therapies are two leading bionic strategies to bypass absent photoreceptors, yet both are limited by a shared "encoding-biointerface" bottleneck: converting external scenes into interpretable neural activity in surviving retinal circuits with adequate selectivity, safety margins, and long-term stability. This review critically compares the two approaches in spatial resolution, neural adaptation, and biosafety, while explicitly distinguishing clinical evidence from preclinical and proof-of-concept studies. Retinal prostheses provide near-term light perception and limited form vision but are constrained by current spread, non-selective pathway/axon recruitment, interface reactions, and cortical decoding burden. Optogenetic restoration offers cell-type-biased reactivation and potentially more physiological processing, but currently remains coupled to external light-delivery hardware and is limited by scattering, heterogeneous transduction, safety-limited irradiance, restricted dynamic range, and adeno-associated virus (AAV)-related inflammatory risk. We highlight emerging integrative directions, including opto-electronic hybrid interfaces, adaptive encoding, broadband subretinal nanomaterial-based photovoltaic nanoprostheses, and experimental acoustic modalities (e.g., focused ultrasound and sonogenetics), alongside ethical and accessibility considerations for translation.},
}

@article {pmid42713229,
year = {2026},
author = {Ho, SC and Lee, IXY and Liu, C and Yu, M and Tan, HC and Tan, GSW and Liu, YC},
title = {Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms.},
journal = {Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques},
volume = {29},
number = {},
pages = {16995},
pmid = {42713229},
issn = {1482-1826},
mesh = {Humans ; *Fenofibrate/therapeutic use/pharmacology/administration & dosage ; Animals ; *Eye Diseases/drug therapy/metabolism ; *Hypolipidemic Agents/pharmacology/therapeutic use/administration & dosage ; PPAR alpha/agonists/metabolism ; },
abstract = {Ophthalmic diseases are a growing global cause of visual impairment, driven by population aging and the rising prevalence of diabetes mellitus. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist widely used for dyslipidemia, has emerged as a candidate for therapeutic repurposing in ophthalmology. This narrative review synthesizes current preclinical and clinical evidence on fenofibrate across anterior and posterior segment diseases, including diabetic corneal neuropathy, diabetic keratopathy, dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, diabetic retinopathy, diabetic macular edema, neovascular age-related macular degeneration, and central retinal artery occlusion. Across ocular disease models, fenofibrate demonstrates neuroprotective, vascular stabilizing, and tissue-remodeling effects. These actions appear to involve modulation of shared pathogenic pathways, including PPARα-dependentregulation of inflammatory signaling, mitochondrial and lipid metabolism, and preservation of epithelial, endothelial, neuronal, and vascular integrity. Clinical evidence is strongest for diabetic retinopathy, where randomized trials support a potential adjunctive role in slowing progression and reducing interventions in patients with early-to-moderate disease. Preliminary clinical evidence for diabetic corneal neuropathy is promising but limited, whereas data for dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, neovascular age-related macular degeneration, and retinal ischemic injury remains preclinical. Emerging experimental ocular delivery strategies may improve local bioavailability while reducing systemic exposure. Overall, fenofibrate represents a biologically plausible adjunctive ophthalmic therapy, but further randomized trials, mechanistic studies, pharmacokinetic evaluation, and long-term safety assessments are required to define its therapeutic role beyond diabetic retinopathy.},
}

Humans
*Fenofibrate/therapeutic use/pharmacology/administration & dosage
Animals
*Eye Diseases/drug therapy/metabolism
*Hypolipidemic Agents/pharmacology/therapeutic use/administration & dosage
PPAR alpha/agonists/metabolism

@article {pmid42714580,
year = {2026},
author = {Hoffmann, S and Liegl, C and Stasik, I and Holz, FG and Liegl, R},
title = {One-year real-world data of intravitreal faricimab in patients with pre-treated neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42714580},
issn = {1435-702X},
abstract = {PURPOSE: To assess one-year real-world outcomes of faricimab therapy in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF agents and managed using a treat-and-extend (TAE) regimen.

METHODS: Patients with treatment-resistant nAMD were switched to faricimab. Functional and structural parameters, including best-corrected visual acuity (BCVA in logMAR), foveal centre point (FCP in µm), central subfield retinal thickness (CSRT in µm), and macular volume (MV in mm³), were recorded over a one-year observation period.

RESULTS: Seventy eyes from 59 patients initiated faricimab therapy between September and December 2022; complete one-year data were available for 60 eyes, with a mean follow-up of 391 ± 20 days. Prior to switching, patients had received an average of 42.4 ± 25.2 anti-VEGF injections over 70.8 ± 45.4 months. Significant structural improvements were observed: FCP decreased from 359 ± 165 μm to 283 ± 132 μm, CSRT from 414 ± 153 μm to 343 ± 116 μm, and macular volume from 2.74 ± 0.67 mm³ to 2.46 ± 0.49 mm³ (all p < 0.001). The mean injection interval increased from 5.8 ± 1.8 weeks to 8.2 ± 3.3 weeks (p < 0.001), indicating improved disease control. BCVA remained stable (0.45 ± 0.37 logMAR vs. 0.44 ± 0.39 logMAR; p = 0.35). At the end of follow-up, 37% of eyes achieved a completely dry macula with no residual intra-, subretinal, or sub-RPE fluid. Two eyes developed mild anterior chamber inflammation, which resolved fully under topical corticosteroids.

CONCLUSION: Switching to faricimab in recalcitrant, heavily pretreated nAMD may yield meaningful structural improvements while stabilizing visual acuity.},
}

@article {pmid42714745,
year = {2026},
author = {Sugisawa, T and Nishi, Y and Imaizumi, H and Aoki, S and Miki, A and Kishi, M and Yamauchi, T and Nagasato, D and Ozawa, Y and Haruta, M and Kato, N and Matsubara, H and Yasukawa, T and Kato, A and Terasaki, H and Hirano, T and Iesato, Y and Tsujinaka, H and Murakami, T and Mitamura, Y and Wakuta, M and Kimura, K and Shimura, M and Gomi, F},
title = {Changes in demographics and treatment trends in neovascular age-related macular degeneration during the COVID-19 pandemic in Japan.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42714745},
issn = {1613-2246},
abstract = {PURPOSE: To elucidate changes in the management of neovascular age-related macular degeneration (nAMD) in Japan during the COVID-19 pandemic .

STUDY DESIGN: Retrospective cohort study.

METHODS: We conducted a multicenter retrospective cohort study of patients newly examined at 16 retina specialist facilities from January 2017 to March 2021. Baseline findings and 3-year follow-up data were compared between pre-pandemic (2017-February 2020) and post-pandemic (March 2020-March 2021) groups.

RESULTS: Analysis of 2271 patients with nAMD revealed a significant decrease in the number of patients examined at hospitals during the COVID-19 pandemic period (p = 0.011), along with a higher proportion of patients who had received treatment within the previous year at local clinics. Baseline ocular findings showed no significant differences between the pre- and post-pandemic groups. Loss to follow-up increased through the second year of the pandemic period (first year, p = 0.0012; second year, p = 0.023). No significant differences were observed during follow-up in visual acuity, central retinal thickness, or number of anti-vascular endothelial growth factor injections. However, in the post-pandemic period the frequency of photodynamic therapy tended to decrease, and examination visits decreased significantly (p = 0.0038).

CONCLUSION: The number of nAMD patients treated in hospitals was lower in the post-pandemic period, and the proportion managed initially in local clinics increased. Although baseline and follow-up characteristics remained largely similar, the use of photodynamic therapy and the number of follow-up visits declined. These findings suggest a shift in the initial nAMD management from hospitals to local clinics during the early post-pandemic period.},
}

@article {pmid42562649,
year = {2026},
author = {Demirayak, P and Fleming, LL and Stewart, P and Chua, R and Visscher, KM},
title = {Increased Attentive Use Is Linked to More Idiosyncratic Functional Connections.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {46},
number = {36},
pages = {},
doi = {10.1523/JNEUROSCI.2178-25.2026},
pmid = {42562649},
issn = {1529-2401},
mesh = {Humans ; Female ; Male ; *Attention/physiology ; Adult ; Magnetic Resonance Imaging ; *Nerve Net/physiology/diagnostic imaging ; *Brain/physiology/diagnostic imaging ; Middle Aged ; Brain Mapping ; },
abstract = {Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brain's complexity, multiple network changes could each move the system toward optimality. Standard approaches examine each connection independently; these studies have often shown considerable interindividual variability and modest effects (Marek et al., 2022). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how "idiosyncratic" the pattern is. We examined how the idiosyncrasy of whole-brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (who use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person to person in healthy vision controls (14 females, 9 males). In a second set of analyses, we examined the brains of people with central vision loss (11 females, 10 males) who use a portion of peripheral vision [the preferred retinal locus (PRL)] more frequently for attention-demanding tasks in their daily lives. The cortical representation of the PRL exhibits more idiosyncratic connections, compared with a control brain region or compared with the same brain region in matched healthy vision controls. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole-brain connections.},
}

Humans
Female
Male
*Attention/physiology
Adult
Magnetic Resonance Imaging
*Nerve Net/physiology/diagnostic imaging
*Brain/physiology/diagnostic imaging
Middle Aged
Brain Mapping

@article {pmid42705516,
year = {2026},
author = {Kim, M and Park, Y and Choi, SW and Lee, EK and Park, UC and Park, KH and Yoon, CK},
title = {Reticular Pseudodrusen Subtypes and Their Interaction With Soft Drusen: Longitudinal Structure-Function Analysis.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.047},
pmid = {42705516},
issn = {1879-1891},
abstract = {PURPOSE: To evaluate longitudinal structure-function relationships of reticular pseudodrusen (RPD) subtypes and their interaction with soft drusen (SD) on retinal sensitivity (RS) in intermediate age-related macular degeneration (AMD).

DESIGN: Retrospective cohort study.

SUBJECTS: Forty-six eyes of 28 patients diagnosed with intermediate AMD or RPD who underwent microperimetry at two time points 6 to 12 months apart.

METHODS: RPD presence and subtype (dot or ribbon) and SD were assessed individually at each of 37 Early Treatment Diabetic Retinopathy Study grid test points on co-registered multimodal imaging. Linear mixed-effects models estimated baseline RS and its change by drusen composition, with test-point location as a fixed effect and adjustment for clinical covariates, plus baseline RS for the change analysis.

MAIN OUTCOME MEASURES: Change in RS over follow-up and baseline RS, according to drusen composition.

RESULTS: At baseline, ribbon-type RPD regions showed lower RS than lesion-free regions (mean difference 0.72 ± 0.24 dB, P = .002), whereas dot-type RPD did not differ (P = .120); SD was independently associated with reduced RS (P = .021). No baseline RPD subtype × SD interaction was observed. Longitudinally, a significant interaction was found (P = .005): regions with both ribbon-type RPD and SD showed the greatest RS decline, whereas RPD subtypes did not differ without SD (all P > .9).

CONCLUSIONS: The functional impact of RPD varies by subtype and coexistence with SD. Ribbon-type RPD is associated with greater RS impairment, particularly when combined with SD, highlighting the importance of lesion phenotype in functional risk assessment.},
}

@article {pmid42706530,
year = {2026},
author = {Ranabhat, S and Shakya, K and Bajgai, P and Singh, L and Shrestha, S and Agrawal, R},
title = {Retinal and choroidal morphometric analysis in fellow eye of unilateral wet age related macular degeneration using optical coherence tomography angiography.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42706530},
issn = {1471-2415},
mesh = {Humans ; Male ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/pathology ; Cross-Sectional Studies ; Female ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; *Wet Macular Degeneration/diagnosis/pathology/diagnostic imaging ; Middle Aged ; Fundus Oculi ; Visual Acuity ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) when associated with macular neovascularization can cause severe visual morbidity. This study aims to evaluate the retinal and choroidal microvascular alterations using optical coherence tomography angiography (OCTA) in eyes with unilateral wet age-related macular degeneration (AMD) termed as "affected eye" (AE) and compare it with their "fellow eyes" (FE).

METHODS: This cross-sectional study included 60 patients (120 eyes) with age over 50 years. Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexuses (SCP), deep capillary plexus (DCP) and avascular slab were assessed using OCTA. Enhanced depth imaging was used to evaluate subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI).

RESULTS: The mean age was 73.9 ± 9.54 years (51-89 years) with 51.7% male. Quantitative OCTA analysis showed no significant inter-eye differences in VD or PD in SCP or DCP (p > 0.05). However, FAZ was significantly enlarged in AE compared with FE in SCP (0.91 ± 0.40 vs. 0.64 ± 0.20 mm²; p < 0.001) and DCP (p < 0.001). FAZ enlargement in the avascular slab was not statistically significant (p 0.20). Pattern I macular neovascularization (MNV) was significantly associated with the shape (p 0.026), presence of anastomoses (p 0.029), and overall activity scores (p 0.001). Inter-eye differences choroidal parameters were statistically significant for SFCT (p 0.019), haller layer (p 0.014) and CVI (p < 0.001). AE status was significantly associated with age (p 0.04) smoking (p 0.01), and lens status (p 0.05).

CONCLUSION: FAZ enlargement demonstrated greater inter-eye separation and higher discriminatory performance compared than density-based OCTA parameters and may reflect localized microvascular or structural alteration in unilateral neovascular AMD. OCTA-based assessment of FE may aid in detecting early microvascular alterations and guiding timely intervention, which may be potentiated by retinal and choroidal vascular or structural remodeling.},
}

Humans
Male
*Tomography, Optical Coherence/methods
*Choroid/blood supply/pathology
Cross-Sectional Studies
Female
*Fluorescein Angiography/methods
Aged, 80 and over
*Retinal Vessels/pathology/diagnostic imaging
Aged
*Wet Macular Degeneration/diagnosis/pathology/diagnostic imaging
Middle Aged
Fundus Oculi
Visual Acuity

@article {pmid42709011,
year = {2026},
author = {Blix, T and Løkken, JFT and Steffensen, LA and Sæther, EM and Husum, YS and Ødegaard, EM and Bragadottir, R and Moe, MC and Jørstad, ØK},
title = {Impact of faricimab and high-dose aflibercept on treatment demand in a tertiary ophthalmic centre in Norway.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70240},
pmid = {42709011},
issn = {1755-3768},
abstract = {PURPOSE: To evaluate the impact of introducing faricimab and high-dose aflibercept on intravitreal injection (IVI) demand and treatment costs for retinal diseases in a large tertiary retina centre.

METHODS: This retrospective longitudinal registry study included all anti-VEGF treatment episodes at Oslo University Hospital, Norway, between 2021 and 2025. Annual injection volumes, treatment patterns, and costs were assessed following the introduction of faricimab (2023) and high-dose aflibercept (2025). High-dose aflibercept was generally administered at 50 μL (5.7 mg). Costs components were estimated using a health-economic model.

RESULTS: A total of 142 960 treatment episodes comprising 169 700 IVIs in 7865 patients (mean age 75.5 years, 56.6% female) were included. Macular degeneration was the most common diagnosis. Treated patients increased from 4148 in 2021 to 4982 in 2025. Injections increased from 31 780 in 2021 to a peak of 35 508 in 2024 before declining to 33 696 in 2025, while mean injections per patient decreased from 7.7 to 6.8. Following its introduction in 2023, faricimab became the most used agent. Off-label bevacizumab proportion decreased from 50.6% in 2021 to 30.0% in 2025. Mean treatment cost per patient increased from NOK 38029 in 2021 to NOK 40187 in 2025 (+5.7%), while total treatment costs increased from NOK 158 million to NOK 200 million (+26.9%).

CONCLUSIONS: The introduction of faricimab and high-dose aflibercept was associated with reduced per-patient treatment intensity, while the treated population continued to increase. Longer-acting anti-VEGF drugs may reduce pressure on retinal services by lowering injection frequency; however, their introduction was associated with higher overall costs.},
}

@article {pmid42698447,
year = {2026},
author = {Wan, Z and Chen, X and Gao, F and Shi, F and Dai, R and Peng, Q and Wei, Q},
title = {Faricimab in neovascular age-related macular degeneration: aqueous humor cytokine profiling and biomarker correlations.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1927909},
pmid = {42698447},
issn = {2296-858X},
abstract = {PURPOSE: To investigate aqueous humor cytokine profile changes in neovascular age-related macular degeneration (nAMD) patients before and after intravitreal faricimab injection, and their correlation with biomarkers.

METHODS: Twenty-three nAMD patients and 10 cataract controls were enrolled. Aqueous humor was collected from nAMD patients at baseline and 12 weeks post-faricimab injection, and from controls during phacoemulsification. Twelve cytokines were quantified via multiplex bead-based immunoassay. OCTA measured central macular thickness (CMT) and retinal vessel density in nAMD eyes.

RESULTS: Baseline vascular endothelial growth factor (VEGF), Angiopoietin-2 (Ang-2) and HGF levels were higher in nAMD patients than controls. Post-treatment, VEGF and Ang-2 decreased below control levels, while hepatocyte growth factor (HGF) and interferon gamma protein 10 (IP-10) increased significantly. Reductions in Ang-2/VEGF correlated positively with decreased CMT and whole retinal thickness, with concurrent improvements in best-corrected visual acuity. Elevated IP-10 showed a correlative association with reduced superficial foveal vessel density.

CONCLUSION: Faricimab dual-blockades VEGF/Ang-2, reducing their aqueous levels, improving CMT/whole retinal thickness and visual acuity. However, post-treatment HGF/IP-10 upregulation indicates compensatory inflammatory-angiogenic remodeling. IP-10 may serve as a potential correlative biomarker linked to subclinical capillary rarefaction. Future studies should explore combined anti-IP-10 therapy or extended dosing intervals to preserve foveal vasculature while maintaining anti-leakage efficacy.},
}

@article {pmid42698711,
year = {2026},
author = {Liu, Y and Li, Z and Ma, Y and Liu, Y},
title = {Targeting angiogenesis: advances in the design and engineered applications of nanobodies.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1912560},
pmid = {42698711},
issn = {1664-3224},
mesh = {Humans ; *Single-Domain Antibodies/therapeutic use/immunology/genetics/chemistry ; Animals ; *Neovascularization, Pathologic/immunology/drug therapy ; Neoplasms/immunology/therapy ; Protein Engineering ; *Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Angiogenesis is a fundamental physiological process; however, its pathological dysregulation drives diseases such as solid tumors, wet age-related macular degeneration, and rheumatoid arthritis. Although clinically effective, conventional anti-angiogenic monoclonal antibodies are limited by poor tissue penetration, off-target toxicities, and susceptibility to compensatory resistance. This review systematically examines the structural advantages and engineering strategies of nanobodies (Nbs) targeting angiogenesis-related pathways. Advanced engineering approaches, such as AI-assisted humanization and multivalent assembly, effectively mitigate immunogenicity and extend serum half-life. Furthermore, multispecific designs can simultaneously block compensatory pathways to circumvent resistance. Moreover, preclinical studies indicate that integrating these molecules into site-specific nanobody-drug conjugates and targeted delivery vehicles may improve therapeutic precision and local drug accumulation; however, their long-term safety, manufacturability, and clinical benefit remain to be established. Functionalizing Nbs with radionuclides or fluorophores may enable the development of novel theranostic platforms that support real-time molecular imaging and image-guided surgery. In parallel, nanobody-based CAR-T (Nb-CAR-T) cells facilitate the targeted remodeling of the disease microenvironment. Ultimately, this review highlights the value of engineered Nbs as a highly programmable and transformative platform. By overcoming key limitations of conventional antibodies, engineered nanobodies open new avenues for precise, multi-dimensional interventions in solid tumors. Their potential in certain non-neoplastic angiogenic diseases is emerging but requires further validation.},
}

Humans
*Single-Domain Antibodies/therapeutic use/immunology/genetics/chemistry
Animals
*Neovascularization, Pathologic/immunology/drug therapy
Neoplasms/immunology/therapy
Protein Engineering
*Angiogenesis Inhibitors/therapeutic use

@article {pmid42700909,
year = {2026},
author = {Zhang, X and Lin, Y and Cheng, J and Yan, M and Huang, Z and Ye, Y and Song, Y},
title = {Association Between Subretinal Hyperreflective Material and OCTA-Derived Macular Neovascularization Morphology in Treatment-Naive Neovascular Age-Related Macular Degeneration.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105645},
doi = {10.1016/j.pdpdt.2026.105645},
pmid = {42700909},
issn = {1873-1597},
abstract = {PURPOSE: To evaluate whether baseline subretinal hyperreflective material (SHRM) status is associated with optical coherence tomography angiography (OCTA)-derived macular neovascularization (MNV) vessel density, complexity, and ramification in treatment-naive neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective, single-center, cross-sectional imaging study included 89 eyes from 89 treatment-naive patients with nAMD. One eye per patient was included to avoid inter-eye correlation. SHRM was assessed on baseline structural optical coherence tomography (OCT). OCTA images were acquired using 6 × 6 mm scans, and MNV lesions were manually delineated as regions of interest. The primary OCTA-derived parameters were MNV vessel density, fractal dimension, and branch points. Multivariable linear regression models were adjusted for age, sex, central macular thickness, and MNV type.

RESULTS: SHRM was present in 56 eyes (62.9%) and absent in 33 eyes (37.1%). Compared with SHRM-negative eyes, SHRM-positive eyes had worse baseline best-corrected visual acuity (BCVA) (P < 0.001), greater central macular thickness (P < 0.001), and higher frequencies of subretinal fluid, intraretinal fluid, and retinal hemorrhage. SHRM-positive eyes also showed higher MNV vessel density (0.262 vs. 0.196; P = 0.017), fractal dimension (1.568 vs. 1.487; P = 0.024), and branch points (140.5 vs. 91.0; P = 0.035). After adjustment, SHRM remained associated with higher MNV vessel density (β = 0.045; P = 0.042), fractal dimension (β = 0.077; P = 0.029), and branch points (β = 98.74; P = 0.045).

CONCLUSIONS: These findings suggest that SHRM-positive status is associated with a denser, more complex, and more ramified OCTA-derived MNV vascular phenotype at baseline in treatment-naive nAMD.},
}

@article {pmid42701791,
year = {2026},
author = {Chen, Z and Liu, J and Cheng, S and Xu, Q},
title = {The Evolving Burden of Age-Related Macular Degeneration in China (1990-2023): Insights from an Aging Society and the Anti-VEGF Era.},
journal = {Clinical epidemiology},
volume = {18},
number = {},
pages = {621990},
pmid = {42701791},
issn = {1179-1349},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. China bears the world's largest AMD burden. This study analyzes the evolving AMD burden in China (1990-2023) and the impact of anti-VEGF therapy.

METHODS: We analyzed data from the Global Burden of Disease (GBD) 2023 study using joinpoint regression, decomposition analysis, and Bayesian modeling. A supplementary meta-analysis of single-arm studies was conducted to assess anti-VEGF efficacy in Chinese patients.

RESULTS: From 1990 to 2023, China's age-standardized prevalence rate (ASPR) and disability-adjusted life year rate (ASDR) for AMD decreased by -0.67% and -1.48% annually, respectively. In 2023, China accounted for 35.82% of global cases and 30.25% of global DALYs. A supplementary meta-analysis of 13 single-arm observational studies showed a pooled efficacy rate of 74% for anti-VEGF drugs in China, albeit with substantial heterogeneity (I[2] = 93.07%), warranting cautious interpretation. The accelerated decline in ASDR after 2011 coincided temporally with the clinical introduction and subsequent insurance coverage of anti-VEGF therapy. Projections indicate a continued decline in burden through 2038.

CONCLUSION: Despite a declining age-standardized burden, China's absolute AMD burden remains substantial due to rapid population aging and other challenges. The temporal association between anti-VEGF therapy availability and the accelerated burden decline suggests a potential contribution of this treatment, though causality cannot be directly inferred from this ecological analysis. The observed trends likely reflect multiple factors, including improved healthcare access, early diagnosis, socioeconomic development, and anti-VEGF therapy. Comprehensive strategies focusing on prevention and equitable healthcare access are needed.},
}

@article {pmid42703379,
year = {2026},
author = {Zeaiter, M and Jaber, H and Gharbi, K and Fernandes, SMB and Mchaik, J and Ahmed, M and Hassan, A and Hammoud, AA},
title = {Faricimab in the Treatment of Retinal Disease: A Narrative Review.},
journal = {Cureus},
volume = {18},
number = {8},
pages = {e114098},
pmid = {42703379},
issn = {2168-8184},
abstract = {Retinal and choroidal diseases, including diabetic macular edema, neovascular age-related macular degeneration, retinal vein occlusion, and polypoidal choroidal vasculopathy, remain a significant cause of visual impairment around the world, especially among elderly . Although anti-vascular endothelial growth factor (anti-VEGF) therapy remains the standard of care, it is limited by its side effect profile, resistance, and high injection burden. This underscores the need for a more optimal and possible replacement. Faricimab is an emerging bispecific antibody targeting VEGF-A and angiopoietin-2, addressing both angiogenesis and vascular permeability by modulating the tyrosine kinase with immunoglobulin-like domains-2 pathway. This literature review synthesizes information from preclinical studies and randomized controlled trials. It focuses on the molecular reasoning behind the use of faricimab and the safety profile compared with anti-VEGF monotherapy.},
}

@article {pmid42705337,
year = {2026},
author = {Kim, DE and Kim, M and Im, M},
title = {Perceptual characteristics of scotomas modulate visual performance under simulated prosthetic vision.},
journal = {Journal of neural engineering},
volume = {},
number = {},
pages = {},
doi = {10.1088/1741-2552/aea36b},
pmid = {42705337},
issn = {1741-2552},
abstract = {Retinal prostheses aim to restore vision in patients blinded by photoreceptor degeneration, yet functional outcomes vary substantially across individuals. Scotomas-regions of reduced or absent visual sensitivity-are a defining feature of retinal degenerative diseases, but their perceptual status is often underappreciated in the design and evaluation of prosthetic vision. Here, we investigated how differences in scotoma perception influence perceptual visual task performance and perceptual representations. Approach. Psychophysical experiments were conducted using a virtual reality (VR) platform that simulated visual field deficits characteristic of retinal degeneration, including age-related macular degeneration (AMD). Two different scotoma conditions, perceptually filled-in (invisible) and solid black, were implemented in a head-mounted display (HMD) environment developed in Unity 3D Game Engine. Participants performed visual tasks while behavioral measures, including accuracy, response time, and eye-tracking metrics, were recorded and analyzed. Main Results. Despite identical visual inputs, task performance showed statistically significant differences depending on the perceptual characteristics (i.e., background-matching vs. black) of the simulated scotoma. Critically, the spatial-frequency performance cost on response time was abolished selectively under the black-scotoma-with-phosphene condition (χ[2](3) = 8.72, p = 0.033), whereas it remained significant under all invisible scotoma conditions, indicating that a perceptually distinct scotoma background enhances the detectability of phosphene signals. These differences were reflected corroborated by systematic divergences in gaze trajectory length and terminal fixation location across conditions. Significance. Our findings suggest that variability in scotoma perception constitutes an important, yet underexplored, factor contributing to inter-individual differences in the effectiveness of retinal prosthetic stimulation. Accounting for perceptual properties of scotomas may provide a framework for optimizing stimulation strategies and improving functional outcomes of future retinal prostheses.},
}

@article {pmid42697260,
year = {2026},
author = {Pourbagherkhah, P and Jaldian, HB},
title = {Biomarkers for Detecting and Predicting Macular Neovascularization in Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography: A Systematic Review.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105637},
doi = {10.1016/j.pdpdt.2026.105637},
pmid = {42697260},
issn = {1873-1597},
abstract = {PURPOSE: This systematic review evaluates the role of optical coherence tomography angiography (OCTA)-based biomarkers in detecting and predicting macular neovascularization (MNV) in age-related macular degeneration (ARMD).

METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus and Google Scholar up to 20 May 2026, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed original cohort and cross-sectional studies reporting OCTA-derived quantitative and qualitative biomarkers associated with MNV.

RESULTS: A total of 203 articles were initially identified, with 11 studies meeting the eligibility criteria, comprising 642 eyes. Key OCTA biomarkers included vascular density, MNV area, total vessel length, and choroidal vascularity index, which demonstrated strong associations with disease activity and progression.

CONCLUSION: OCTA-derived biomarkers offer a non-invasive and effective means for detecting and monitoring MNV in ARMD. Despite current challenges in standardization and interpretation, integrating these biomarkers into clinical practice could improve early diagnosis and personalized treatment strategies.},
}

@article {pmid42697271,
year = {2026},
author = {Kardo, H and Garweg, RA and Imbach, L and Garweg, JG},
title = {Longitudinal Changes in Inner Retinal Layers in Treatment-Naïve Neovascular AMD During Intravitreal Anti-VEGF Therapy.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.08.031},
pmid = {42697271},
issn = {2468-6530},
abstract = {PURPOSE: To investigate longitudinal changes in retinal nerve fiber layer (RNFL) and ganglion cell- inner plexiform layer (GC-IPL) thickness in treatment-naïve neovascular age-related macular degeneration (nAMD) under intravitreal anti-VEGF therapy (IVT), compared with untreated fellow eyes with dry AMD (dAMD).

DESIGN: Retrospective single-center cohort study.

SUBJECTS: Consecutive patients with treatment-naïve nAMD receiving anti-VEGF therapy under a treat-and-extend regimen and a minimum follow-up of 24 months were included. Untreated fellow eyes with dAMD served as controls.

METHODS: RNFL and GC-IPL thickness were assessed longitudinally using spectral-domain optical coherence tomography and RetinAI analysis. Best-corrected visual acuity (BCVA) and structural retinal changes were evaluated over time. Linear mixed-effects models were used to assess factors associated with retinal layer changes.

MAIN OUTCOME MEASURES: Longitudinal changes in RNFL thickness, GC-IPL thickness, and BCVA.

RESULTS: In nAMD eyes, median RNFL thickness in the 3 mm ring zone decreased from 32.3 μm (30.1-35.4) at baseline to 30.9 μm (29.0-33.4; adjusted P < .001) after the loading phase and remained stable thereafter (all adjusted P > .05), with a similar pattern observed in fellow dAMD eyes. In contrast, GC-IPL thickness progressively declined in both groups. In nAMD eyes, median GC-IPL thickness decreased from 89.1 μm (81.9-94.9) at baseline to 85.1 μm (77.7-90.2) after loading (adjusted P < .001), followed by continued thinning throughout follow-up. BCVA in nAMD eyes improved after loading with a median gain of 4.8 ETDRS letters (0-10.2; adjusted P < .001), remained stable for up to 3 years, and gradually declined thereafter. Mixed-effects modeling showed RNFL thickness was associated with injection number, whereas GC-IPL loss was associated with age and follow-up duration, independent of injection number or sex.

CONCLUSIONS: The regression in RNFL and GC-IPL thickness during the loading phase in eyes with nAMD may reflect the resolution of pre-treatment swelling. RNFL thickness remained stable thereafter, while GC-IPL thickness and BCVA declined after loading similarly to fellow eyes with dAMD. According to the mixed-effects model, GC-IPL thinning appears linked to progression of the underlying degenerative process, whereas RNFL thickness appears comparatively preserved.},
}

@article {pmid42697425,
year = {2026},
author = {Sun, X and Zhang, G and Feng, X and Hong, Z and Qu, Y and Li, M and Xia, Z and Xu, J and Bachwenkizi, J and Lam, H and Wang, Y and Honda, Y and Hashizume, M and Chen, R and Wu, Z and Ji, JS and Liang, D and Guo, Y and Kan, H and Jia, H and Wong, TY},
title = {Exposome for Ocular Diseases: From Exposure Evidence to Causality and Actionable Prevention.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101524},
doi = {10.1016/j.preteyeres.2026.101524},
pmid = {42697425},
issn = {1873-1635},
abstract = {The exposome, defined as the totality of external exposures individuals experience throughout the lifespan and the internal biological responses they trigger, is increasingly recognized as a major, modifiable determinant of health. The eye is uniquely vulnerable to exposome risk factors because it comprises an external interface directly exposed to the environment, a transparent lens highly sensitive to cumulative oxidative injury, and metabolically active retina prone to inflammation and vascular dysregulation. Research linking ocular diseases to air pollution, climate and weather factors, heavy metals, persistent organic pollutants, and emerging threats such as micro-/nanoplastics has expanded rapidly, yet the evidence remains fragmented and lacks systematic integration. In this review, we propose an anatomy-informed ocular exposome atlas along the visual axis to comprehensively evaluate evidence from clinical studies, pathological mechanisms, and intervention strategies across major disease groups-including ocular surface diseases, cataract, refractive errors, glaucoma, and retinal diseases. We further integrate cross-disease mechanistic pathways (oxidative stress, cellular responses, inflammation, immune reactions) and discuss causality. Finally, we identify priority research directions and provide actionable recommendations for prevention and policy.},
}

@article {pmid42696011,
year = {2026},
author = {Kozlov, M and Sadeghi, E and Chhablani, J},
title = {Adoption patterns of anti-vascular endothelial growth factor therapies in retinal disease.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42696011},
issn = {1435-702X},
abstract = {PURPOSE: To characterize real-world adoption patterns of anti-vascular endothelial growth factor (anti-VEGF) therapies across retinal vascular diseases.

METHODS: This retrospective cohort study identified patients diagnosed with exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) within TriNetX. Monthly utilization of ranibizumab, bevacizumab, aflibercept, brolucizumab, and faricimab was measured across each indication. To provide absolute treatment context, we also determined the annual number of unique patients within each disease cohort with at least one documented exposure to any evaluated anti-VEGF agent.

RESULTS: The cohorts included 138,384 AMD patients, 322,865 DME patients, and 105,605 RVO patients. Aflibercept demonstrated sustained long-term utilization across all three indications, whereas faricimab showed rapid early uptake after its introduction. Ranibizumab utilization declined over time, while brolucizumab demonstrated limited and transient uptake. The annual number of patients receiving anti-VEGF treatment increased substantially over the observation period and reached 16,319 in AMD, 12,105 in DME, and 6,873 in RVO in 2023.

CONCLUSION: Real-world adoption of anti-VEGF therapies differs markedly across retinal diseases and agents. Aflibercept demonstrated sustained long-term use, while faricimab showed rapid early uptake. Changes in agent-specific utilization occurred alongside substantial growth in the absolute number of treated patients over the study period, underscoring the importance of interpreting drug-specific trajectories in the context of overall treatment activity.},
}

@article {pmid42690636,
year = {2026},
author = {Chen, S and Li, Y and Xuan, M and Xiong, R and Tan, S and Wang, W},
title = {Longitudinal Trajectories of 3-Dimensional Eye Shape and Pathological Sequelae in High Myopia.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42690636},
issn = {2168-6173},
abstract = {IMPORTANCE: The highly myopic eye remodels in 3 dimensions, but the longitudinal trajectories of globe shape and their associations with sight-threatening outcomes remain poorly defined.

OBJECTIVE: To characterize 15-year 3-dimensional (3D) remodeling trajectories of highly myopic globes and examine their associations with baseline features and ocular outcomes.

This 15-year 3D magnetic resonance imaging (MRI) cohort substudy was nested within the Zhongshan High Myopia Cohort. Thirty participants (60 eyes) with bilateral high myopia (spherical equivalent refraction, -6.00 D or worse) randomly drawn from 95 participants imaged in September 2011 were rescanned in September 2025.

EXPOSURES: Orbital 3D MRI reconstructions were classified into 6 globe-shape categories. Paired classifications, global enlargement, and staphyloma status defined 5 remodeling patterns: quiescence, proportional expansion, focal emergence, focal progression, and shape transition.

MAIN OUTCOMES AND MEASURES: Distribution of remodeling patterns and their associations with myopic macular degeneration (MMD), myopic traction maculopathy (MTM), posterior staphyloma (PS), visual acuity, and visual field indices.

RESULTS: Among the 30 included participants, the mean (SD) age was 37.30 (15.89) years, and 16 (53.3%) participants were women. The 60 eyes were classified as quiescent (21 [35.0%]), proportional expansion (12 [20.0%]), focal emergence (14 [23.3%]), focal progression (6 [10.0%]), or shape transition (7 [11.7%]). No deformed eye reverted to spheroidal. Pattern distribution was associated with baseline age and contour: 10 of 12 eyes (83.3%) of individuals younger than 20 years underwent proportional expansion, whereas 13 of 24 eyes (54.2%) of individuals aged 40 years and older followed focal progression or shape transition. Eyes with focal emergence had the largest best-corrected visual acuity decline (0.26 logMAR) and mean deviation worsening (-3.50 dB), and eyes with shape transition had the largest pattern standard deviation increasing (1.95 dB). At similar axial elongation, eyes developing focal deformation had higher frequencies of MMD progression (91.7%; 95% CI, 74.2-97.7 vs 58.8%; 95% CI, 36.0-78.4; P = .02), incident or progressive PS (91.7%; 95% CI, 74.2-97.7 vs 17.6%; 95% CI, 6.2-41.0; P < .001), and MTM (58.3%; 95% CI, 38.8-75.5 vs 11.8%; 95% CI, 3.3-34.3; P = .003).

CONCLUSIONS AND RELEVANCE: Highly myopic globes followed age- and geometry-associated trajectories linked to outcomes beyond axial elongation. These 2-time-point findings potentially support 3D shape analysis as a candidate framework for individualized surveillance, pending prospective validation.},
}

@article {pmid42693542,
year = {2026},
author = {Jung, W and Lee, JJ and Cho, Y and Min, KA and Yun, HY and Lee, S and Yang, J and Chae, JW},
title = {Determination of Human Effective Dose via Translational Ocular Modeling: Clinical Translation of a Novel Topical Agent Using PBPK.},
journal = {Clinical and translational science},
volume = {19},
number = {9},
pages = {e70717},
pmid = {42693542},
issn = {1752-8062},
support = {RS-2022-00155857//Korea Government/ ; RS-2023-00278597//Korea Government/ ; RS-2022-NR069643//Korea Government/ ; RS-2022-NR070856//Korea Government/ ; RS-2021-KE001333//Core Technology Development Project for Environmental Diseases Prevention and Management/ ; //Korea Ministry of Environment (MOE)/ ; //Korea Machine Learning Ledger Orchestration for Drug Discovery Project (K-MELLODDY)/ ; RS-2024-00460694//Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea/ ; 2710008763//Korea Institute of Toxicology (KIT) Research Program/ ; KK-2401-01//Korea Institute of Toxicology (KIT) Research Program/ ; //Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)/ ; RS-2024-00336984//Ministry of Health & Welfare, Republic of Korea/ ; RS-2025-02306055//Ministry of Health & Welfare, Republic of Korea/ ; RS-2024-00434342//Korea Institute for Advancement of Technology (KIAT)/ ; //National Research Foundation of Korea (NRF)/ ; RS-2025-25397599//Ministry of Education/ ; //EyeBioKorea/ ; },
mesh = {Humans ; Animals ; Rabbits ; Mice ; *Models, Biological ; *Macular Degeneration/drug therapy ; Translational Research, Biomedical ; Dose-Response Relationship, Drug ; *Ophthalmic Solutions/administration & dosage/pharmacokinetics ; Computer Simulation ; Tissue Distribution ; Species Specificity ; Male ; },
abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of vision loss, and human dose selection for ocular therapeutics remains a key translational challenge. We developed a physiologically based pharmacokinetic (PBPK) model for EB-203 to guide dose selection by translating preclinical ocular tissue exposure to human. PK data were obtained from mouse and rabbit studies and human plasma PK from a phase I trial. The model incorporated species-specific ocular physiology, drug permeability, and pharmacokinetics, and was implemented using an open-source PBPK modeling software (MoBi, version 12.2, Open Systems Pharmacology). Drug-specific model parameters were estimated using mouse and rabbit plasma and ocular tissue concentration data. Human plasma PK data from a Phase I clinical trial were then used to estimate human-specific systemic clearance, and human ocular tissue concentrations were subsequently predicted by the model. Simulated human retinal drug concentrations (AUC, Cmax, and Cavr) under multiple dosing regimens were evaluated against preclinical efficacy thresholds to determine the optimal dosing strategy. The model adequately described drug disposition across species, with most predicted PK parameters falling within a 2-fold error of the observed data. Simulations suggested that a 4% four-times-daily dosing regimen in humans achieves retinal exposure comparable to the efficacious mouse concentrations. No significant systemic accumulation was observed, indicating a favorable safety profile. This PBPK framework provides a practical approach for predicting human ocular drug exposure and can be adapted to other compounds or ocular indications in the absence of direct tissue sampling. These results support further clinical evaluation of EB-203 for the treatment of wAMD.},
}

Humans
Animals
Rabbits
Mice
*Models, Biological
*Macular Degeneration/drug therapy
Translational Research, Biomedical
Dose-Response Relationship, Drug
*Ophthalmic Solutions/administration & dosage/pharmacokinetics
Computer Simulation
Tissue Distribution
Species Specificity
Male

@article {pmid42694158,
year = {2026},
author = {Jin, E and Zhu, X and Li, S and Zhao, M and Miao, H and Qian, T},
title = {Short-term morphological and functional outcomes of intravitreal faricimab for chorioretinal disorders: a real-world study in a Chinese population.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1909782},
pmid = {42694158},
issn = {2296-858X},
abstract = {OBJECTIVE: To evaluate the real-world efficacy and safety of the bispecific antibody faricimab in Chinese patients with neocascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema secondary to retinal vascular occlusion (RVO-ME).

METHODS: This retrospective, single-center study included 63 patients (74 eyes: 47 nAMD, 19 DME, 8 RVO-ME); no subjects dropped out. Of the 74 eyes, 37.8% were treatment-naïve and 62.2% were treatment-experienced. All eyes received intravitreal faricimab 6 mg in a three-dose loading regimen followed by pro re nata (PRN) retreatment. Best-corrected visual acuity (BCVA, ETDRS letters) and central macular thickness (CMT) were assessed at baseline, 1 month, 3 months, and final follow-up (mean follow-up, 23.9 ± 12.3 weeks). Subgroup analyses by prior treatment status were performed.

RESULTS: Faricimab was associated with anatomical and functional improvements. In nAMD, treatment-naïve patients (n = 17) showed significant BCVA improvement (62.52 ± 5.80 to 71.05 ± 15.68 letters, P = 0.037) and CMT reduction (477.86 ± 189.45 to 324.19 ± 137.62 μm, P = 0.001) at final follow-up. Previously-treated nAMD patients (n = 30) showed only a transient CMT reduction at 3 months (P = 0.022) without sustained visual improvement. After the first injection, intraretinal fluid resolved in 90% of nAMD eyes that had IRF at baseline. After three loading doses, complete resolution of subretinal fluid and pigment epithelial detachment (PED) occurred in 66.7% and 31.3% of eyes, respectively. In DME, treatment-naïve patients (n = 9) achieved early BCVA improvement at 1 month (P = 0.0273) and sustained benefit at final follow-up (P = 0.0180), whereas previously-treated patients (n = 10) showed delayed improvement at 3 months in both BCVA and CMT (P = 0.0117 and 0.0195). In RVO-ME, BCVA improved significantly at 3 months and final follow-up (P = 0.018 and 0.028), whereas CMT showed a nonsignificant decrease. No significant ocular or systemic adverse events were observed.

CONCLUSION: In this short-term real-world study comprising three exploratory disease-specific cohorts of Chinese patients, faricimab was associated with favorable anatomical and functional outcomes and was well tolerated, with the most pronounced benefit in treatment-naïve nAMD eyes. Responses in DME and RVO-ME were more variable and appeared to be influenced by prior treatment history; these subgroup analyses were exploratory, and larger prospective studies are warranted.},
}

@article {pmid42684442,
year = {2026},
author = {Bandello, F and Borrelli, E and De Falco, S and Invernizzi, A and Lanzetta, P and Lupidi, M and Midena, E and Ricci, F and , },
title = {Aflibercept 8 mg for diabetic macular edema and neovascular age-related macular degeneration: an italian expert consensus paper.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42684442},
issn = {1435-702X},
abstract = {PURPOSE: To provide consensus recommendations on the clinical use of aflibercept 8 mg in managing neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in the real-world setting.

METHODS: A modified Delphi study was undertaken, involving ophthalmologists from specialized centers in Italy, to gauge consensus on statements related to the use of aflibercept 8 mg in nAMD and DME. Two initial rounds of online surveys were conducted, followed by 2 workshops to assess the clinical feasibility of selected statements and identify the behavioral drivers and barriers to their adoption in practice. Consensus was defined as ≥ 75% agreement ('strongly agree' or 'somewhat agree').

RESULTS: Consensus was reached for 30 initial statements, following refinement and discussion. Of these, 12 statements were analyzed and discussed at the behavioral workshop. Statements covered clinical differentiation of aflibercept 2 mg and 8 mg, treatment initiation in aflibercept-naïve patients, switching to aflibercept 8 mg, optimal aflibercept 8 mg maintenance, and safety considerations. There was expert group consensus that aflibercept 8 mg represents a viable treatment option with an extended injection interval for patients with nAMD or DME, with the possibility of improving treatment adherence, and therefore outcomes. Experts also discussed practical considerations in Italy and offered evidence-based guidance.

CONCLUSION: Experts agreed that aflibercept 8 mg is a treatment option for both nAMD and DME with the potential to improve treatment adherence. Although real-world data are limited, experts offered guidance on the management of nAMD and DME in the context of aflibercept 8 mg.},
}

@article {pmid42685076,
year = {2026},
author = {Cheng, FF and Mou, H and Liu, Z and Zhang, CJ and Zhuang, YY and Wu, Z and Wen, XR and Xue, A and Zhang, X and Yang, J and Jin, ZB},
title = {Genetic evidence and cross-species functional characterization implicate CNN2 in age-related macular degeneration susceptibility.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {36},
pages = {e2533682123},
doi = {10.1073/pnas.2533682123},
pmid = {42685076},
issn = {1091-6490},
support = {82125007//MOST | National Natural Science Foundation of China (NSFC)/ ; 92368206//MOST | National Natural Science Foundation of China (NSFC)/ ; CX23YZ14//Chinese Institutes for Medical Research/ ; BRWEP2024W172050100//Beijing Research Ward Excellence Program/ ; PWD&RPP-MRI//Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes/ ; JYY2023-6//Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes/ ; U23A20165//MOST | National Natural Science Foundation of China (NSFC)/ ; 2024SSYS0032//"Pioneer" and "Leading Goose" R&D Program of Zhejiang/ ; 2022SDXHDX0001//"Pioneer" and "Leading Goose" R&D Program of Zhejiang/ ; },
mesh = {Animals ; *Genetic Predisposition to Disease ; *Macular Degeneration/genetics/pathology/metabolism ; Zebrafish ; Quantitative Trait Loci ; Genome-Wide Association Study ; Mice ; Humans ; Cytoskeletal Proteins/genetics/metabolism ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the aging population globally. Although genome-wide association studies (GWAS) have identified many AMD susceptibility loci, the genes and mechanisms underlying many of these associations remain unresolved. Here, we integrated expression quantitative trait locus (eQTL) data with AMD GWAS to prioritize nine putative genes. Through in vivo screening in zebrafish, we demonstrated that the downregulation of cnn2 and sarm1 expression led to ocular structural abnormalities and visual functional impairment. Subsequent mouse model studies confirmed that Cnn2 deficiency affected photoreceptor structure and function, impaired contrast sensitivity, and caused abnormalities in cone cell immunostaining. Given that CNN2 is predominantly expressed in endothelial cells, we propose that endothelial dysfunction may cascade to impair photoreceptor function. Collectively, through in silico prioritization and cross-species functional characterization, we identify CNN2 as a candidate susceptibility gene in AMD pathogenesis, providing vital underlying mechanistic insights.},
}

Animals
*Genetic Predisposition to Disease
*Macular Degeneration/genetics/pathology/metabolism
Zebrafish
Quantitative Trait Loci
Genome-Wide Association Study
Mice
Humans
Cytoskeletal Proteins/genetics/metabolism
Disease Models, Animal

@article {pmid42686244,
year = {2026},
author = {Manikya, S and Vadhithala, V and Kumar, R and Nainwal, P},
title = {Re: Holz et al.: Adherence to intravitreal aflibercept in neovascular age-related macular degeneration: 24-month results from the ANDROMEDA Study (Ophthalmol. Retina. 2026;10:241-249).},
journal = {Ophthalmology. Retina},
volume = {10},
number = {9},
pages = {e81-e82},
doi = {10.1016/j.oret.2026.06.013},
pmid = {42686244},
issn = {2468-6530},
}

@article {pmid42687065,
year = {2026},
author = {Attia, SA and Tse, AM and Ramirez, AD and Izadiar, M and Liu, Y and Guo, H and Albanese, A and Cohn, W and MacKay, AW and Seidler, PM and Kannan, R and Sreekumar, PG and MacKay, JA},
title = {αB-crystallin elastin-like polypeptides for sustained ocular drug delivery.},
journal = {Drug delivery and translational research},
volume = {},
number = {},
pages = {},
pmid = {42687065},
issn = {2190-3948},
abstract = {The unfolded protein response (UPR) has been mechanistically implicated in multiple ocular disorders, including age-related macular degeneration (AMD). Therapeutic intervention using an αB-crystallin-derived 'mini-cry' chaperone peptide has potential to restore proteostasis; however, its low molecular weight results in rapid ocular clearance. To prolong mini-cry's ocular effects, our team linked it with elastin-like polypeptides (ELPs). ELPs are thermoresponsive polymers that phase-separate into microscale coacervates. Provided ELPs do not interfere with biological activity, cry-ELPs could prolong intraocular retention and improve therapeutic effect. This study compares two cry-ELPs (cry-SI and cry-V96) designed to phase-separate following intravitreal administration. First, chaperone activity was assessed using tau protein aggregation assays, demonstrating that cry-V96 exhibited superior inhibition of tau seeding and fibril disaggregation. Second, modulation of the UPR was assessed in human retinal pigment epithelium cells using tunicamycin-induced stress. Both constructs suppressed PERK/ATF-4/CHOP signaling, with cry-V96 showing the most robust attenuation of ER stress. Third, cellular uptake and subcellular localization were analyzed by biochemical fractionation and Western blotting, revealing enhanced cellular uptake and association and stress-dependent nuclear localization of cry-ELPs, compared to controls. Fourth, the lead construct, cry-V96, was evaluated in vivo in rabbit eyes, where it formed a sustained intravitreal depot, exhibited prolonged retention, and showed no evidence of ocular toxicity by fluorescence imaging and optical coherence tomography (OCT). Finally, proteomic profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 59 proteins selectively enriched by cry-V96, implicating pathways involved in proteostasis, intracellular trafficking, and stress adaptation. Collectively, these findings establish cry-ELPs as multifunctional molecules that combine potent chaperone activity with sustained ocular delivery, providing a promising strategy for targeting UPR dysregulation in AMD and related degenerative diseases.},
}

@article {pmid42687870,
year = {2026},
author = {Mandal, D and Roy, A and Chen, X and Zhong, JF and Kim, ES},
title = {Microfluidic platform for nanoliter qPCR of several retinal pigment epithelial (RPE) cells.},
journal = {Journal of micromechanics and microengineering : structures, devices, and systems},
volume = {36},
number = {9},
pages = {095001},
pmid = {42687870},
issn = {0960-1317},
abstract = {The clinical implant of stem cell-derived retinal pigment epithelium (RPE) monolayer for age-related macular degeneration requires rigorous validation of the monolayer's cellular maturity. Conventional bulk molecular assays lack the sensitivity to resolve cellular heterogeneity and are prone to damaging the RPE monolayer. This study developed and validated an automated nanoliter-scale microfluidic platform for single-cell transcriptomic quality control of engineered RPE monolayers. A compact polydimethylsiloxane -based microfluidic platform was developed to generate monodisperse 10 nL RPE cell cDNA droplets and 90 nL quantitative PCR (qPCR) reagent droplets using dual-focused-flow geometries. Deterministic droplet fusion was achieved via direct current electrocoalescence, enabling ∼100% merging efficiency. An auxiliary co-flow spacing mechanism was implemented to prevent secondary coalescence during downstream transport. Automated droplet collection into oil-filled 96-well plates was achieved through a custom two-dimensional gantry system, and droplet volume consistency was verified using a Python-based computer vision algorithm. Biological validation was conducted using H14 human embryonic stem cell-derived RPE cells targeting β-actin and lineage-specific markers MITF1, MITF2, PEDF, and PMEL17. The platform demonstrated stable generation and deterministic merging of nanoliter droplets, yielding uniform 100 nL reaction volumes suitable for qPCR analysis. Automated volumetric verification confirmed high droplet uniformity and reliability. Gene expression analysis revealed robust detection of housekeeping and lineage-specific genes at nanoliter scales. These findings demonstrated the feasibility of performing nanoliter-scale qPCR using the proposed microfluidic workflow. The workflow enabled reliable detection of extremely low quantities of nucleic acid using a widely available commercial qPCR platform, providing a practical and accessible approach for routine laboratory and translational research applications. The system-maintained assay sensitivity while significantly reducing reagent consumption and sample input. This automated microfluidic platform enabled reproducible, sample-efficient, single-cell transcriptomic validation of stem cell-derived RPE monolayers. By integrating droplet generation, deterministic merging, automated collection, and computational verification, the system addressed key limitations of bulk molecular quality control of RPE monolayers. This work established a scalable and cost-effective nanoliter qPCR framework for high-resolution molecular quality assurance of regenerative cell therapies.},
}

@article {pmid42687910,
year = {2026},
author = {Swaroop, A and Marchal, C and Gaur, M and Kumari, A and Mohan, S and Brooks, M and Jaeger, C and Advani, J and Campello, L and English, M and Singh, N and Diaz, X},
title = {Enhanced chromatin compaction is associated with de novo expression of a nuclear microprotein, global loss of H3 acetylation and local transcriptional changes in retinal rod photoreceptors.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-10017071/v1},
pmid = {42687910},
issn = {2693-5015},
abstract = {We have limited understanding of how aging alters gene expression and remodels cellular architecture in post-mitotic neurons. The inverted nuclear organization of mouse rod photoreceptors provides a unique model to gain mechanistic insights into age-associated decline in neuronal function. We have generated and integrated multi-omic datasets including 3D-genome topology, histone modifications, chromatin accessibility, DNA methylation and transcriptome of rod photoreceptors from young- and aged-mice. We show that aging drives global chromatin compaction, with regional alterations enriched at active chromatin. Epigenomic and transcriptional changes broadly correlate with chromatin dynamics as validated by high resolution microscopy. We uncover a megabase-sized genomic region with multi-level alterations, including de novo transcription of Gm7239, which encodes a functional microprotein carrying histone acetyltransferase-inhibitor domain. Overexpression of Gm7239 is associated with global loss of histone H3 acetylation, highlighting a potential new axis of genomic regulation in aging. Finally, we identify multiple significant local transcriptional alterations in non-annotated regions and genes associated with age-related macular degeneration. Our studies link age-related chromatin landscape changes with gene expression that may influence rod function and vulnerability to diseases.},
}

@article {pmid42681078,
year = {2026},
author = {Cheong, KX and Jiang, Y and Xu, X and Htoon, HM and Foo, LL and Lamoureux, EL and Hoang, QV and Lan, W and Saw, SM},
title = {Two-Year Fundus Progression in Highly Myopic Eyes in the Aier-SERI High Myopia Adult Cohort Study.},
journal = {Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {},
number = {},
pages = {},
pmid = {42681078},
issn = {1475-1313},
support = {2024RC5002, 2023RC1079//Science and Technology Innovation Program of Hunan Province, China/ ; JRDUKY004900//Duke-NUS Distinguished Professorship grant/ ; },
abstract = {PURPOSE: To evaluate 2 year fundus progression and associated factors in adults in the Aier-SERI High Myopia cohort in Changsha, China.

METHODS: A total of 367 adult high myopes (spherical equivalent [SE] ≤ -5.0D) underwent baseline and 2 year assessments, including colour fundus photography graded by the Meta-analysis for Pathologic Myopia (META-PM) classification. Progression was defined as advancement to a higher category, enlargement of atrophy or development/worsening of plus lesions. Associations were analysed using multivariable generalised estimating equation (GEE) logistic regression adjusting for age, sex, SE or axial length (AL) and baseline META-PM category.

RESULTS: In this cohort (mean age: 45.2 ± 7.3 years), fundus progression occurred in 31/734 eyes (4.2%, 27 participants). Of 37 lesion changes in 31 eyes, the most frequent changes were enlargement of patchy atrophy (51.4%), followed by diffuse atrophy (16.2%) and lacquer crack extension (16.2%). Fuchs' spot expansion and category progression were less common (8.1% each). In GEE models, progression was associated with more myopic SE (per -1D, odds ratio [OR]: 1.21; 95% confidence interval [CI]: 1.14-1.29, p < 0.001), longer AL (per 1-mm, OR: 1.96; 95% CI: 1.64-2.34, p < 0.001) and older age (per year, OR: 1.06; 95% CI: 1.02-1.11, p < 0.01). Eyes with baseline Category 3 lesions had markedly higher odds of progression (OR: 85.55; 95% CI: 25.07-291.93, p < 0.001).

CONCLUSIONS: Over 2 years, fundus progression in adult highly myopes occurred mainly in those with advanced atrophy at baseline and was associated with greater myopia, longer AL and older age. Eyes of Categories 0-1 remained stable, suggesting a threshold for accelerated degeneration.},
}

@article {pmid42681693,
year = {2026},
author = {Ruiz-Medrano, J and Zamorano, M and de Alboran, CM and Ruiz-Moreno, JM},
title = {Two-year real-world effectiveness of faricimab after treatment switch in neovascular age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {12},
number = {1},
pages = {},
pmid = {42681693},
issn = {2056-9920},
abstract = {PURPOSE: To evaluate the 2-year real-world outcomes of switching to intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF agents and unable to extend treatment intervals (TI) beyond 12 weeks.

METHODS: Prospective cohort study including patients with nAMD managed under a treat-and-extend regimen who required frequent anti-VEGF injections (< 12-week intervals) to maintain retinal dryness. Patients were switched to faricimab without a loading phase and followed for a minimum of 2 years. TI were extended in 4-week increments based on anatomical response. The primary outcome was change in TIl; secondary outcomes included change in best-corrected visual acuity (BCVA) and identification of predictors of response. "Optimal responders" were defined as eyes achieving ≥ 8-week interval extension.

RESULTS: A total of 110 eyes from 97 patients were included (mean age 78.7 ± 9.8 years). Prior to switching, the mean TI was 6.18 ± 2.05 weeks, which increased significantly to 13.61 ± 5.62 weeks at the last follow-up visit (p < 0.001). BCVA remained stable over 2 years (0.42 ± 0.24 vs. 0.43 ± 0.25; p = 0.0117). At final follow-up, 68.2% of eyes achieved intervals ≥ 12 weeks, 20.0% ≥16 weeks, and 24.6% reached ≥ 20-week intervals. Overall, 89.1% of eyes experienced interval extension. Optimal responders accounted for 47.3% of eyes and were significantly younger and had received fewer prior injections (p < 0.05).

CONCLUSIONS: Switching to faricimab in previous treated nAMD patients enabled meaningful extension of TI over 2 years while maintaining stable visual acuity. These findings support faricimab as an effective strategy to reduce treatment burden in patients who are difficult to extend with prior anti-VEGF therapies.},
}

@article {pmid42682018,
year = {2026},
author = {Swan, J and Gagneux, P},
title = {Glycosylation of the retina.},
journal = {Biochemical Society transactions},
volume = {54},
number = {9},
pages = {1183-1192},
pmid = {42682018},
issn = {1470-8752},
support = {M2023003F//BrightFocus Foundation (BFF)/ ; },
mesh = {Glycosylation ; Humans ; *Retina/metabolism ; Animals ; Polysaccharides/metabolism ; Proteoglycans/metabolism ; Glycosphingolipids/metabolism ; Retinal Diseases/metabolism ; },
abstract = {Unlike the cornea and tear fluid, glycosylation within the retina remains remarkably underexplored. This review highlights the diverse roles of glycans in retinal development and vision, with a focus on major glycan classes, including glycosphingolipids (GSLs; glycans attached to lipids), N- and O-linked glycans on proteins, glycosaminoglycans (GAGs) on proteoglycans, O-mannosylated proteoglycans, and intracellular O-GlcNAcylation. Together, these components provide a comprehensive framework for understanding glycan-mediated processes in retinal biology. Current knowledge of the retinal glycosylation nanolandscape, primarily derived from lectin binding and anti-glycan antibody studies, is summarised. The review also examines the roles of altered glycosylation in immune regulation and retinal diseases such as retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy. Finally, key gaps in knowledge and priority areas for future research are discussed. The retina remains understudied with regard to the complex patterns of glycosylation. Alterations of these patterns could represent consequences or be driving pathology, given the well-established roles of glycan patterns in development and homeostasis in other tissues.},
}

Glycosylation
Humans
*Retina/metabolism
Animals
Polysaccharides/metabolism
Proteoglycans/metabolism
Glycosphingolipids/metabolism
Retinal Diseases/metabolism

@article {pmid42683940,
year = {2026},
author = {Guo, CW and Zhao, AH and Kaelber, D and Singh, RP and Talcott, KE},
title = {Effect of Hormone Replacement Therapy on Risk of Age-related Macular Degeneration Among an Aggregate Health Record Cohort.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/23258160-20260813-03},
pmid = {42683940},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: Estrogen in hormone replacement therapy (HRT) exerts anti-inflammatory effects believed to oppose age-related macular degeneration (AMD) pathogenesis, but whether HRT can be protective against AMD is contested. The aim of the study was to evaluate the association between HRT use and the risk of development and progression of AMD in postmenopausal women.

PATIENTS AND METHODS: This was a retrospective cohort study utilizing ICD-10 codes for HRT usage and rates of AMD development and progression.

RESULTS: There was a decreased risk of developing AMD in patients more than 60 years of age at 5 years (RR 0.72, 95% CI: 0.63-0.82) and 8 years (0.68, 0.60-0.76) after HRT initiation. Patients more than 75 years of age also demonstrated a reduced risk of developing AMD after 5 years (0.70, 0.60-0.82) and 8 years (0.64, 0.56-0.74) of HRT use. Patients more than 75 years of age had a reduced risk of progression to exudative AMD at 8 years (0.66, 0.49-0.89) after HRT initiation.

CONCLUSION: HRT may be associated with a decreased risk of developing AMD, with continued effects at more chronic timepoints after HRT initiation.},
}

@article {pmid42676384,
year = {2026},
author = {Wang, MH and Lee, SMY and Wang, Y and Alves, JC and Xie, R and He, Y and Hou, G and Fang, X and Yu, Y and Cai, X and Zheng, S and Liu, J and Cheang, C and Kuok, KI and Qin, S},
title = {Artificial intelligence for precision therapeutics in age-related macular degeneration: current advances, challenges, and future directions.},
journal = {Frontiers in artificial intelligence},
volume = {9},
number = {},
pages = {1822604},
pmid = {42676384},
issn = {2624-8212},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is characterized by substantial clinical, imaging, and molecular heterogeneity that complicates disease prediction and therapeutic management. Recent advances in artificial intelligence (AI) and precision therapeutics have created new opportunities for more individualized and data-driven AMD care. AI models trained on multimodal datasets-including fundus photography, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), genetic susceptibility loci (e.g., CFH, ARMS2/HTRA1, C3, CFI, and APOE), and longitudinal clinical information-have demonstrated promising capability in early disease detection, progression forecasting, biomarker identification, and prediction of treatment response. These developments align closely with emerging precision therapeutic strategies, including optimized anti-vascular endothelial growth factor (anti-VEGF) regimens, complement-targeted therapies, gene-based interventions, and stem cell-associated regenerative approaches. This review provides a translational overview of AI-enabled precision therapeutics in AMD, with emphasis on multimodal biomarker integration, individualized therapeutic stratification, longitudinal disease monitoring, and clinically interpretable AI systems. Importantly, we further propose a Five-Level Clinical Readiness and Translational Utility Framework for AI in AMD Precision Therapeutics, categorizing AI applications according to evidence strength, clinical maturity, validation status, interpretability, and real-world implementation potential. The framework distinguishes near-reference-standard imaging AI systems, advanced clinical decision-support tools, emerging multimodal precision therapeutic AI, supportive workflow-oriented AI systems, and currently limited or unsuitable AI applications. Despite substantial progress, important translational barriers remain, including limited external validation, retrospective study designs, dataset heterogeneity, domain shift, insufficient explainability, regulatory uncertainty, and challenges related to workflow integration and real-world clinical deployment. Future advances in multimodal longitudinal AI, explainable AI, federated learning, digital health platforms, and multi-omics integration may facilitate a transition from reactive disease management toward more proactive, predictive, and personalized ophthalmic care. Collectively, AI-enabled precision therapeutics may help establish a more scalable and clinically integrated framework for individualized AMD management and future precision ophthalmology.},
}

@article {pmid42676770,
year = {2026},
author = {Verma, V and Gupta, S and Singh, P and Karkhur, S and Behera, PR},
title = {Global Patterns of Visual Disability and Low Vision Aid Prescription: A Systematic Review.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e113756},
pmid = {42676770},
issn = {2168-8184},
abstract = {Visual disability remains a major global public health challenge, particularly among individuals with irreversible ocular diseases where medical or surgical treatment cannot restore functional vision. Low-vision rehabilitation (LVR), including the prescription of low-vision aids (LVAs), plays a critical role in optimizing residual vision and improving quality of life; however, patterns of visual disability and LVA utilization vary widely across populations and healthcare settings. This systematic review was conducted in accordance with PRISMA 2020 guidelines to evaluate patterns of visual disability and the prescription, utilisation, and functional outcomes of low-vision aids across diverse patient populations. Electronic databases, including PubMed, Scopus, EMBASE, and the Cochrane Library, along with Google Scholar and citation tracking, were searched for studies published between 2000 and 2025. Observational studies, randomized or crossover trials, service audits, and rehabilitation reports assessing low-vision rehabilitation or assistive devices were included. Of 975 records identified, 19 studies met the inclusion criteria. Retinal diseases such as age-related macular degeneration, diabetic maculopathy, and inherited retinal dystrophies were the predominant causes of visual disability in adults, whereas congenital and developmental conditions were more common in pediatric populations. Optical LVAs, particularly high-add spectacles and magnifiers, were the most frequently prescribed devices, while electronic and wearable aids demonstrated superior task-specific performance but lower real-world uptake due to cost and usability barriers. Telerehabilitation showed functional outcomes comparable to in-clinic training. Overall, low-vision aids significantly improve functional outcomes across a wide spectrum of visual disabilities, and a multimodal, patient-centered rehabilitation model integrating optical, electronic, and tele-rehabilitation approaches is essential to enhance accessibility, service reach, and effectiveness.},
}

@article {pmid42676855,
year = {2026},
author = {Xiang, Y and Kou, J and Cao, H and Zhang, Y and Cheng, H and Wang, T and Jiang, J and Pan, S and Kang, J and Ding, Y and Wan, W and Zheng, S and Li, M and Huang, X and Hu, K},
title = {Nano-drops of biomimetic macromolecular drugs based on macrophage membranes for targeted treatment of fundus diseases.},
journal = {Materials today. Bio},
volume = {40},
number = {},
pages = {103577},
pmid = {42676855},
issn = {2590-0064},
abstract = {Ocular fundus diseases-including age-related macular degeneration and diabetic retinopathy-are leading causes of irreversible vision loss worldwide. Current macromolecular therapies require frequent intravitreal injections, which increase patient burden and complication risks. To address these limitations, we engineered a macrophage membrane-biomimetic nanovesicle encapsulating ranibizumab (designated M@R) for noninvasive ocular delivery and selective targeting of inflammatory lesions in the posterior segment. In vitro studies demonstrated that M@R retained potent cytokine-scavenging activity against key pro-inflammatory mediators, and the macrophage membrane coating significantly enhanced transcytosis-mediated transport of ranibizumab across ocular epithelial barriers. Ex vivo and in vivo studies confirmed that M@R is capable of noninvasive traversal of ocular barriers, achieving targeted delivery to inflammatory lesions within the fundus. In a laser-induced choroidal neovascularization (CNV) mouse model, topical ocular administration of M@R significantly reduced both the area and thickness of CNV, attributable to its dual anti-inflammatory and anti-VEGF activities. Although multiple dosing was required to achieve therapeutic efficacy comparable to that of a single intravitreal ranibizumab injection, M@R exhibited markedly improved safety profiles, with no observable local ocular toxicity or systemic adverse effects following repeated administration. Collectively, these findings establish macrophage membrane-coated nanovesicles as a promising platform for barrier-penetrating, inflammation-targeted delivery of biologics in the treatment of fundus diseases.},
}

@article {pmid42676917,
year = {2026},
author = {Shen, Y and Xu, X and Yang, Y and Song, Y and Liu, F and Zhao, F},
title = {The COPD-driven "lung-eye axis": mechanisms and clinical evidence of ocular disease.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1893979},
pmid = {42676917},
issn = {2296-858X},
abstract = {COPD is a chronic systemic disease marked by ongoing airflow obstruction, sustained inflammation, and increased oxidative stress, whose pathological impact extends far beyond the lungs. Growing data suggest that COPD impacts the eye via chronic systemic inflammation, intermittent or persistent hypoxia, oxidative stress, and endothelial dysfunction, establishing a cross-system pathological connection termed the "lung-eye axis." Evidence from clinical and experimental studies indicates potential associations between COPD and key ophthalmic conditions, such as dry eye disease, cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. The underlying mechanisms largely involve the retina and optic nerve, which rely heavily on oxygenation and microvascular homeostasis, highlighting them as prime ocular targets of COPD systemic effects. The application of noninvasive imaging, such as OCT and OCTA, offers quantitative and objective preliminary evidence for the lung-eye axis, indicating that ocular imaging could function as a surrogate marker of systemic disease burden in COPD. Despite being largely cross-sectional and methodologically constrained, the proposed "COPD-driven lung-eye axis" framework offers a cross-organ perspective for understanding the systemic characteristics of COPD. There is an urgent need for large, prospective, multicenter studies combining pulmonary function tests, blood gas measurements, inflammatory biomarker profiling, and multimodal ocular imaging to establish causal links and clinical utility, providing novel strategies for precision stratification and early intervention of COPD-related systemic complications.},
}

@article {pmid42677513,
year = {2026},
author = {Li, Y and Li, B and Zou, D and Zeng, Z and Guo, B and Gong, W and Deng, K and Wang, Z and Zhou, H and Zhou, Y and Xu, X},
title = {Stereospecific Peptide-Polysaccharide Conjugates Enable Noninvasive Therapy of Neovascular Age-Related Macular Degeneration.},
journal = {Journal of the American Chemical Society},
volume = {148},
number = {33},
pages = {35467-35483},
doi = {10.1021/jacs.6c05947},
pmid = {42677513},
issn = {1520-5126},
support = {22077028//National Natural Science Foundation of China/ ; 22277023//National Natural Science Foundation of China/ ; 32000995//National Natural Science Foundation of China/ ; 82271110//National Natural Science Foundation of China/ ; 91956105//National Natural Science Foundation of China/ ; 2025JJ50628//Natural Science Foundation of Hunan Province/ ; 20255098//Scientific Research Project of the Hunan Provincial Health Commission/ ; 2025RC3064//Science and Technology Innovation Program of Hunan Province/ ; 2026JJ20024//Outstanding Young Scientists Program of the Natural Science Foundation of Hunan Province/ ; NA//?Furong Scholar? Distinguished Professor Program in Hunan Province/ ; NA//Flexibly Recruited High-End Talent Program of Yunnan Province/ ; SKY24078//Xiangjiang Public Welfare Foundation of Hunan Province/ ; },
mesh = {Animals ; *Peptides/chemistry/pharmacology/therapeutic use ; *Polysaccharides/chemistry/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy/pathology ; Mice ; Humans ; Stereoisomerism ; *Choroidal Neovascularization/drug therapy ; Cell Proliferation/drug effects ; },
abstract = {Therapeutic interventions for posterior segment ocular diseases, including neovascular age-related macular degeneration (nAMD), remain constrained by poor intraocular bioavailability and the need for repeated intravitreal injections. Here, we introduce a noninvasive therapeutic strategy based on stereospecific peptide-polysaccharide conjugates (PPC) for efficient nAMD treatment. A controllable synthetic strategy was established to generate stereospecific L-PPC and D-PPC, among which D-PPC displayed pronounced chirality-dependent bioactivity, characterized by high-affinity binding to integrin receptors and enhanced inhibition of endothelial/epithelial cell proliferation and migration. Following topical administration, D-PPC efficiently overcame ocular barriers and penetrated choroidal lesions while markedly suppressing pathological angiogenesis in a laser-induced choroidal neovascularization mouse model, comparable to that of intravitreal ranibizumab. We elucidated that stereospecific D-PPC modulates key molecular programs in vivo, including T-cell receptor signaling and cell adhesion molecule pathways. Notably, D-PPC exhibited no detectable ocular or systemic toxicity. This study establishes chirality-engineered peptide-polysaccharide conjugates as a noninvasive and effective therapeutic for posterior ocular diseases, providing a structural and mechanistic blueprint for future translational ophthalmic applications.},
}

Animals
*Peptides/chemistry/pharmacology/therapeutic use
*Polysaccharides/chemistry/therapeutic use/pharmacology
*Macular Degeneration/drug therapy/pathology
Mice
Humans
Stereoisomerism
*Choroidal Neovascularization/drug therapy
Cell Proliferation/drug effects

@article {pmid42678546,
year = {2026},
author = {Piszár, I and Buhl, A and Chronopoulos, A and Schloesser, L and Dicke, C and Eter, N and Zimmermann, JA and , and Finger, RP},
title = {[The oregis IVOM registry-Introduction of a registry for the systematic documentation of representative IVOM treatment data from routine treatment of macular diseases in Germany].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42678546},
issn = {2731-7218},
abstract = {BACKGROUND: Intravitreal operative medication injection (IVOM) treatment in routine clinical practice often fails to achieve the treatment outcomes demonstrated in clinical trials. In Germany, comprehensive and representative real-world data on IVOM treatment (IVT) for macular diseases are still lacking.

OBJECTIVE: Against this background the oregis IVOM registry was established as a subregistry of the national oregis registry. The aim is the standardized collection and analysis of the course of IVOM treatment in the clinical routine in Germany, to evaluate long-term outcomes and identify potential areas for optimizing patient care. In this way participating ophthalmological centers can make an active contribution to the evidence-based development of IVOM treatment.

MATERIAL AND METHODS: The oregis IVOM registry is a prospective, noninterventional observational study. Medical routine care data of adult patients receiving IVOM treatment for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO) or choroidal neovascularization (CNV) are collected. Data acquisition is performed via web-based remote data entry into an electronic database using REDCap. Registry structure, datasets and data collection parameters are aligned with the international Fight Retinal Blindness! registry.

CONCLUSION: The oregis IVOM registry provides, for the first time, a nationwide structured platform for the systematic collection and evaluation of real-world IVT data in Germany. It closes an important evidence gap in health services research for IVOM treatment in Germany and enables regional and international comparisons as well as analyses of treatment adherence and real-world care.},
}

@article {pmid42680556,
year = {2026},
author = {Gao, Q and Kuo, D and Amason, J and Lee, T and Rathinavelu, JK and Pajic, M and Hadziahmetovic, M},
title = {Modular multi-task deep learning framework for prediction of treatment initiation in neovascular age-related macular degeneration modular AI for NVAMD treatment initiation study-MANTIS.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328327},
pmid = {42680556},
issn = {1468-2079},
abstract = {PURPOSE: The purpose of this study is to develop a fully automated system for determining the optimal time to begin anti-vascular endothelial growth factor (anti-VEGF) treatment, based on retinal changes observed in optical coherence tomography (OCT) images and visual acuity (VA) scores.

METHODS: This retrospective study included two cohorts: patients with intermediate dry age-related macular degeneration (AMD) who did not progress to neovascular AMD (NVAMD) and those who progressed and received anti-VEGF treatment. Subjects had ≥3 consecutive visits. Two tasks were defined: (1) develop a deep learning (DL) model to identify the need for anti-VEGF treatment and (2) estimate outer retina thickness (ORT) from Bruch's membrane to the outer plexiform layer as an imaging biomarker. A convolutional neural network extracted OCT features related to ORT, and two long short-term memory models were trained on separate datasets to address Task I and II treatments.

RESULTS: A total of 122 patients (207 eyes) were included: 49 in dataset 1 (69 eyes; mean (SD) age 84 (8); 25 (51%) female) and 100 in dataset 2 (138 eyes; 82 (7); 54 (54%) female). Task I performance was evaluated by the model's alignment with clinical decisions on anti-VEGF initiation, and demonstrated area under the receiver operating curve of 0.73 (95% CI 0.59 to 0.87), area under the precision-recall curve of 0.51 (95% CI 0.35 to 0.66), an accuracy of 0.87 (95% CI 0.76 to 0.97), a precision of 0.73 (95% CI 0.59 to 0.87), a sensitivity of 0.69 (95% CI 0.54 to 0.83) and a specificity of 0.92 (95% CI 0.84 to 1.00). Task II achieved NMAE 0.12 (95% CI 0.04 to 0.20).

CONCLUSIONS: This DL framework provides a fully automated approach for determining optimal treatment timing, supporting earlier intervention to preserve VA in NVAMD patients.

TRANSITIONAL RELEVANCE: An accurate DL framework that can help with identifying the best time to initiate therapy for NVAMD.},
}

@article {pmid42669559,
year = {2026},
author = {Telegina, DV and Kutlimetova, AO and Izyurov, AE and Kulikov, AV and Kolosova, NG},
title = {Age-Related Alterations in Retinal Monoamine Neuromodulation during AMD-Like Retinopathy Development in Rats.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {8},
pages = {1406-1416},
doi = {10.1134/S0006297926600870},
pmid = {42669559},
issn = {1608-3040},
mesh = {Animals ; *Retina/metabolism/pathology ; Rats ; *Aging/metabolism ; *Macular Degeneration/metabolism/pathology ; Rats, Wistar ; Monoamine Oxidase/metabolism ; *Biogenic Monoamines/metabolism ; Male ; Dopamine/metabolism ; Tyrosine 3-Monooxygenase/metabolism ; },
abstract = {Aging is the major risk factor for age-related macular degeneration (AMD), a leading cause of vision loss in aging populations. Increasing evidence suggests that alterations of neurotransmitter systems contribute to the pathogenesis of AMD. Although biogenic amines in the retina were first detected over 50 years ago, their age-related dynamics and role in AMD development are still poorly understood. Here, we compare age-related changes in the concentrations of norepinephrine, serotonin, dopamine, and their main metabolites in the retinas of senescence-accelerated OXYS rats that develop an AMD-like retinopathy and Wistar rats. We also assessed activities of monoamine oxidases (MAOs) and tyrosine hydroxylase and compared changes in these activities with transcriptome data on genes associated with biogenic amine pathways. The results revealed that in OXYS rats, retinal aging and progression of AMD-like retinopathy are primarily associated with alterations in the dopaminergic system. Specifically, dopamine and its main metabolite DOPAC were present in the retinas at higher levels than serotonin and 5-hydroxyindoleacetic acid. Furthermore, the development of retinopathy in OXYS rats was accompanied by elevated dopamine and DOPAC levels, decreased MAO activity, and changes in the expression of genes associated with the dopaminergic synapse signaling.},
}

Animals
*Retina/metabolism/pathology
Rats
*Aging/metabolism
*Macular Degeneration/metabolism/pathology
Rats, Wistar
Monoamine Oxidase/metabolism
*Biogenic Monoamines/metabolism
Male
Dopamine/metabolism
Tyrosine 3-Monooxygenase/metabolism

@article {pmid42669560,
year = {2026},
author = {Yakovleva, MA and Kostyukov, AA and Aronshtam, NL and Shilkrot, PM and Borzenok, SA and Kuzmin, VA and Feldman, TB and Dontsov, AE and Ostrovsky, MA},
title = {Age-Related Changes in bis-Retinoids of Lipofuscin Granules in Human Retinal Pigment Epithelium Cells.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {8},
pages = {1417-1431},
doi = {10.1134/S0006297926600985},
pmid = {42669560},
issn = {1608-3040},
mesh = {Humans ; *Lipofuscin/metabolism/chemistry ; *Retinal Pigment Epithelium/metabolism/cytology ; *Retinoids/metabolism/chemistry ; *Aging/metabolism ; Oxidation-Reduction ; Spectrometry, Fluorescence ; },
abstract = {Lipofuscin granules (LGs) in retinal pigment epithelium (RPE) cells contain bis-retinoids and their oxidation and degradation products, rendering them photo- and cytotoxic to intracellular structures. LGs are implicated in the pathogenesis of multiple visual pathologies, including age-related macular degeneration (AMD). They exhibit strong autofluorescence, which has led to the development of fundus autofluorescence (FAF) imaging as a non-invasive diagnostic method in ophthalmology. Spectral analysis of autofluorescence can expand the capabilities of this method, including for preclinical diagnostics, as pathological conditions are often associated with increased proportions of oxidized bis-retinoid derivatives that alter LG autofluorescence parameters. However, limited knowledge of age-dependent changes in LG bis-retinoid composition remains a key limitation. In this study, we combined fluorescence spectroscopy, confocal fluorescence microscopy, and fluorescence lifetime imaging (time-correlated single-photon counting) to demonstrate that, under physiological conditions, aging is accompanied by a progressive increase in the relative abundance of oxidation and degradation products of bis-retinoids in LGs. These findings provide an age-dependent baseline for distinguishing physiological and pathological states, thereby improving the potential of FAF imaging for early (preclinical) diagnosis.},
}

Humans
*Lipofuscin/metabolism/chemistry
*Retinal Pigment Epithelium/metabolism/cytology
*Retinoids/metabolism/chemistry
*Aging/metabolism
Oxidation-Reduction
Spectrometry, Fluorescence

@article {pmid42671233,
year = {2026},
author = {Rosito, A and Caranti, S and Verna, R},
title = {Comparison of adverse events of three anti-VEGF drugs for the treatment of age-related macular degeneration.},
journal = {The Malaysian journal of pathology},
volume = {48},
number = {2},
pages = {267-276},
pmid = {42671233},
issn = {0126-8635},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Ranibizumab/adverse effects/therapeutic use ; *Bevacizumab/adverse effects ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/adverse effects ; Pharmacovigilance ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible central vision loss among elderly individuals in developed countries. The neovascular form of AMD is currently treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, particularly ranibizumab, aflibercept, and bevacizumab. Although these therapies significantly improve visual outcomes, repeated intravitreal administration requires continuous monitoring of ocular and systemic adverse events. This review compares the safety profiles of the three principal anti-VEGF agents used for AMD treatment through analysis of pharmacovigilance data, regulatory reports, and major clinical trials. Particular attention is dedicated to ocular complications, systemic thromboembolic events, and the implications of off-label bevacizumab use. Current evidence suggests an overall comparable efficacy and safety profile among the three agents, although Bevacizumab requires stricter preparation and monitoring protocols because of its off-label use. Pharmacovigilance remains essential for identifying safety signals, supporting regulatory decisions, and optimising therapeutic strategies in ophthalmology.},
}

Humans
*Macular Degeneration/drug therapy
*Angiogenesis Inhibitors/adverse effects/therapeutic use
*Ranibizumab/adverse effects/therapeutic use
*Bevacizumab/adverse effects
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
Receptors, Vascular Endothelial Growth Factor/therapeutic use
*Recombinant Fusion Proteins/adverse effects
Pharmacovigilance

@article {pmid42671884,
year = {2026},
author = {Karaca, I and Tezel, TH},
title = {Systemic Lupus Erythematosus Associated Drusen-like Deposits.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000005005},
pmid = {42671884},
issn = {1539-2864},
}

@article {pmid42672000,
year = {2026},
author = {Forouhari, A and Cheung, CMG and Leng, LL and Gilead, N and Chakravarthy, U and Teo, KYC},
title = {Predicting risk of progression of early to late AMD in the aging eye through imaging and multimodal evaluation: PRIME study protocol.},
journal = {PloS one},
volume = {21},
number = {8},
pages = {e0355953},
pmid = {42672000},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/pathology/diagnosis ; Disease Progression ; Tomography, Optical Coherence ; Female ; Prospective Studies ; Singapore ; Aged ; Male ; Middle Aged ; Longitudinal Studies ; *Multimodal Imaging ; *Aging/pathology ; Visual Acuity ; Risk Factors ; *Eye/diagnostic imaging/pathology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision impairment globally and demonstrates substantial variation regarding progression and clinical subtypes across populations. This paper describes the methodology of our study, designed to establish the natural history of AMD in Asian elderly and to identify predictors of progression from early signs of AMD to late AMD over a 5-year period.

METHODS: This prospective, longitudinal cohort study aims to recruit 1500 participants from community-based cohorts in Singapore, with a follow-up duration of 5 years. Eligible participants are adults aged 55 years or older without severe systemic illness that would preclude participation. At baseline, demographic data and medical history will be collected, and visual acuity will be assessed. A basic imaging protocol including color fundus photography (CFP), optical coherence tomography (OCT), and OCT angiography (OCTA) will be performed. Blood samples will be collected from consenting participants. Images will be graded for early signs of AMD, defined as the presence of pathological findings on CFP, OCT, or OCTA. Participants without early signs of AMD will undergo annual follow-up using the basic imaging protocol. Those with any pathological findings at baseline or during follow-up will undergo an enhanced imaging protocol every 6 months, including ultrawide-field fundus photography, fundus autofluorescence (FAF), OCT, and OCTA. All follow-up visits will be conducted at the Singapore Eye Research Institute (SERI). Multimodal imaging biomarkers will be integrated with clinical, demographic, genetic, and metabolomic data to assess the relative risk of progression and identify potential predictors. The study protocol has been approved by the SingHealth Centralised Institutional Review Board.

DISCUSSION: There is a paucity of data on the progression of AMD and optimal referral thresholds, particularly in Asian populations. This community-based cohort, representative of the general population, will generate one of the largest longitudinal datasets on AMD in Asia and aims to inform future screening strategies. Study registration number: ClinicalTrials.gov Identifier, NCT07653269.},
}

Humans
*Macular Degeneration/diagnostic imaging/pathology/diagnosis
Disease Progression
Tomography, Optical Coherence
Female
Prospective Studies
Singapore
Aged
Male
Middle Aged
Longitudinal Studies
*Multimodal Imaging
*Aging/pathology
Visual Acuity
Risk Factors
*Eye/diagnostic imaging/pathology

@article {pmid42674195,
year = {2026},
author = {Zhang, S and Song, M and Feng, L and Kang, H and Zhao, H and He, J},
title = {Expression, Purification and Antioxidant Activity of Recombinant Human Vascular Endothelial Growth Factor B167 in Escherichia coli.},
journal = {Protein expression and purification},
volume = {},
number = {},
pages = {107001},
doi = {10.1016/j.pep.2026.107001},
pmid = {42674195},
issn = {1096-0279},
abstract = {Age-related macular degeneration (AMD) is a major cause of visual impairment in the elderly, with oxidative stress as its core pathogenesis. Herein, a prokaryotic expression system in Escherichia coli (E. coli) BL21 was developed to yield recombinant human vascular endothelial growth factor B 167(VEGFB167), after systematic optimization of expression and purification parameters, the antioxidant capacity of the target protein was experimentally verified. VEGFB167 was efficiently expressed as inclusion bodies. Following chromatographic purification, the protein purity attained 97% with a concentration of 1.4 mg/mL. Cellular functional assays revealed that VEGFB167 significantly reduced reactive oxygen species, malondialdehyde, and lactate dehydrogenase release, enhanced both superoxide dismutase activity and SOD1/SOD2 gene expression level, inhibited apoptosis, and promoted cell proliferation. These results support further development of VEGFB167 as a biotherapeutic candidate for oxidative injury-triggered illnesses exemplified by AMD.},
}

@article {pmid42674309,
year = {2026},
author = {Sekáč, D and Faura, G and Eikenes, M and Josifovska, N and Petrovski, G and Ellederová, Z and Eide, L},
title = {Polarized Secretion of Mitochondrial DNA by Retinal Pigment Epithelial cells.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111225},
doi = {10.1016/j.exer.2026.111225},
pmid = {42674309},
issn = {1096-0007},
abstract = {Mitochondrial DNA (mtDNA) damage is strongly implicated in age-related macular degeneration (AMD), the most frequent cause of age-mediated visual impairment in developed countries. Here, we investigated and compared the fate of acutely induced oxidation damage in primary retinal pigment epithelial (RPE) cells. The individual RPE clones responded heterogeneously to hydrogen peroxide, both with respect to cell sensitivity and mtDNA damage formation. Peroxide-induced mtDNA damage in human RPE (hRPE) was fully repaired within 4 hours. In parallel, hRPE cells secreted mtDNA from both apical and basolateral surfaces (AP-mtDNA and BL-mtDNA, respectively) independent of peroxide exposure and that could not be explained by detached cells. Most mtDNA was released apically, and the quality of AP-mtDNA was comparable to that of intracellular mtDNA (c-mtDNA). In contrast, BL-mtDNA constituted only 3% of AP-mtDNA, and exhibited a 10-fold higher damage burden. The difference in mtDNA quality suggests a non-random selection of mtDNA molecules to be targeted for export in apical versus basolateral direction. To investigate this, we analyzed epigenetic marks (m.545 methylation) and SNPs (heteroplasmies) in extracellular and cellular mtDNA. We detected differences Extracellular mtDNA in general appeared to be more modified than c-mtDNA and that AP-mtDNA differs from BL-mtDNA, which is indicative of a targeted secretion. Porcine RPEs (pRPEs) from a minipig model of Huntington's Disease associated with impaired epithelial polarity (TgHD) displayed approximately 2-fold higher leakage of AP-mtDNA than control pRPEs, but lower than hRPEs. Together, our data imply that extracellular mtDNA originating from RPE shapes the outer retina and the implications for polar secretion are discussed.},
}

@article {pmid42675158,
year = {2026},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis.},
journal = {Angiogenesis},
volume = {29},
number = {4},
pages = {},
pmid = {42675158},
issn = {1573-7209},
mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Retinal Neovascularization/therapy/genetics/metabolism ; *Capillary Permeability ; Translational Research, Biomedical ; Gene Therapy Agents ; },
abstract = {INTRODUCTION: Retinal diseases driven by pathological angiogenesis and vascular leakage, including neovascular age-related macular degeneration and diabetic retinopathy, impose substantial visual and treatment burdens because current anti-vascular endothelial growth factor (anti-VEGF) therapy requires repeated intravitreal administration. Ocular gene therapy can provide durable intraocular expression of therapeutic proteins and sustained pathway-level disease control.

METHODS: This systematic review and meta-analysis was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Scopus, Web of Science, ScienceDirect, and the Cochrane Library were searched from inception to April 21, 2026. Eligible studies included preclinical, in vitro, and clinical investigations of gene-based interventions targeting retinal angiogenesis, vascular permeability, or related anatomical and treatment-burden outcomes. Random-effects meta-analyses were performed using standardized mean differences (SMDs), mean differences (MDs), and logit event rates.

RESULTS: Twenty-five studies were included. Preclinical gene therapy significantly reduced pathological neovascularization, with a pooled standardized mean difference (SMD) of -1.16 (95% confidence interval [CI], -1.48 to -0.84; p < 0.001) and negligible heterogeneity (I² = 0%). Vascular leakage was also significantly reduced across preclinical experimental studies, with a pooled mean difference (MD) of 0.215 (95% CI, 0.178-0.251; p < 0.001; I[2] = 0%) after directional harmonization. In clinical cohorts, ocular gene therapy significantly reduced central subfield thickness (CST) by -55.30 μm (95% CI, -72.58 to -38.03; p < 0.001) and was associated with reduced anti-vascular endothelial growth factor (anti-VEGF) treatment burden, with a pooled logit event rate of 0.62 (95% CI, 0.20-1.04; p = 0.0039), corresponding to a pooled proportion of approximately 65% of participants meeting study-specific criteria for reduced supplemental anti-VEGF use.

CONCLUSION: Ocular gene therapy shows strong preclinical anti-angiogenic and anti-permeability effects, with emerging clinical evidence of anatomical improvement and reduced anti-VEGF treatment burden in neovascular retinal disease cohorts. Larger disease-specific randomized trials are required to confirm long-term efficacy, safety, and patient selection.},
}

Humans
*Genetic Therapy/methods
Animals
*Retinal Neovascularization/therapy/genetics/metabolism
*Capillary Permeability
Translational Research, Biomedical
Gene Therapy Agents

@article {pmid42675195,
year = {2026},
author = {Mendo, I and Camacho, P and Cabral, D},
title = {Incidental subfoveal choroidal synphlebia in non-neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42675195},
issn = {1476-5454},
}

@article {pmid42675470,
year = {2026},
author = {Hazra, D and Tomita, Y and Uchida, A and Kato, S and Nagai, N and Suzuki, M and Minami, S and Kunimi, H and Ban, N and Kurihara, T and Shinoda, H and Ozawa, Y and Negishi, K},
title = {Long-term visual outcomes and development of retinal pigment epithelial and outer retinal atrophy in neovascular age-related macular degeneration: a comparison of conventional and novel classifications.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42675470},
issn = {1471-2415},
support = {23K15938 and 25K12855//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; *Visual Acuity/physiology ; Female ; Tomography, Optical Coherence/methods ; Male ; Atrophy ; Aged ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/drug therapy/classification/physiopathology/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Retrospective Studies ; Intravitreal Injections ; Polypoidal Choroidal Vasculopathy ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Retinal Photoreceptor Cell Outer Segment/pathology ; },
abstract = {BACKGROUND: Retinal pigment epithelial and outer retinal atrophy (RORA) and complete RORA (cRORA) are major determinants of long-term vision in neovascular age-related macular degeneration (nAMD), but their development across subtypes is poorly defined, especially in Asian populations, in whom pachychoroid-driven disease is common. We compared long-term visual outcomes and atrophy burden between the conventional and novel nAMD classifications.

METHODS: One hundred twenty eyes of 120 treatment-naïve patients with nAMD followed at least six years were classified by conventional (typical nAMD [tAMD], polypoidal choroidal vasculopathy [PCV], retinal angiomatous proliferation [RAP]) and novel (drusen type, pachychoroid type, mixed type, other type) schemes. All eyes received three loading anti-VEGF injections followed by a pro re nata regimen. RORA within the central 1 mm was graded on optical coherence tomography; lesions ≥ 250 μm were defined as cRORA. Visual acuity (VA) retention, atrophy prevalence, and VA around atrophy onset were assessed.

RESULTS: Mean age was 78.0 ± 9.2 years and overall VA retention was 71%. VA retention did not differ among conventional subtypes, but under the novel classification was significantly lower in the drusen type and higher in the pachychoroid type (P < 0.01). VA declined significantly after both RORA and cRORA onset (both P < 0.001). Final RORA/cRORA prevalence was 44.4%/29.6% in tAMD, 50.0%/28.3% in PCV, 83.3%/50.0% in RAP and 76.9%/61.5% in the drusen type, in which cRORA was highest (P < 0.05).

CONCLUSIONS: The novel classification distinguished long-term visual outcomes that the conventional classification did not: the drusen type showed the poorest VA retention and highest cRORA prevalence, whereas the pachychoroid type fared best.},
}

Humans
*Retinal Pigment Epithelium/pathology
*Visual Acuity/physiology
Female
Tomography, Optical Coherence/methods
Male
Atrophy
Aged
Fluorescein Angiography/methods
*Wet Macular Degeneration/drug therapy/classification/physiopathology/diagnosis
Angiogenesis Inhibitors/therapeutic use
Aged, 80 and over
Fundus Oculi
Follow-Up Studies
Retrospective Studies
Intravitreal Injections
Polypoidal Choroidal Vasculopathy
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Retinal Photoreceptor Cell Outer Segment/pathology

@article {pmid42667403,
year = {2026},
author = {Hasegawa, T and Yagi, R and Fujita, H and Nishimaki, R and Asami, H and Orio, Y and Hiranuma, Y and Saima, Y and Taguchi, R and Tanaka, Y and Kaburaki, T and Kakehashi, A and Nakagawa, S},
title = {Bilateral choroidal thinning during unilateral aflibercept for neovascular age-related macular degeneration: 5-year mixed-effects analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42667403},
issn = {1435-702X},
support = {24K12750//Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS)/ ; 25K12854//Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS)/ ; },
abstract = {PURPOSE: To evaluate 5-year choroidal changes in eyes with unilateral neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVA) and to compare longitudinal changes among treated, fellow untreated, and control eyes using mixed-effects modeling.

METHODS: Sixteen patients with unilateral nAMD (16 treated and 16 fellow untreated eyes) and 20 age-matched and sex-matched control eyes were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), central choroidal thickness (CCT), and choroidal vascularity index (CVI) were assessed. Absolute and proportional CCT changes were analyzed. Annual rates of change were estimated using linear mixed-effects models.

RESULTS: Over 5 years, control eyes showed mild age-related choroidal thinning (- 3.7 μm/year). In contrast, CCT declined significantly faster in treated eyes (- 11.5 μm/year; p < 0.01 vs. control); fellow untreated eyes also demonstrated accelerated thinning (- 8.2 μm/year; p < 0.05 vs. control). Proportional analyses showed a similar graded pattern. BCVA worsened and CST decreased in treated eyes, while remaining stable in fellow eyes. CVI increased modestly and similarly in treated and fellow eyes (approximately + 0.8%/year).

CONCLUSION: In this 5-year three-group longitudinal analysis, treated eyes showed the greatest annual reduction in CCT, fellow untreated eyes showed an intermediate reduction, and age-matched control eyes showed the smallest decline. The inclusion of a control group indicated that fellow-eye thinning exceeded that expected from physiological aging alone, supporting bilateral choroidal change during long-term unilateral IVA therapy.},
}

@article {pmid42668221,
year = {2026},
author = {Holt, C and Neidert, C and Gedtal, M and Virgili, G and Hogg, R and Qureshi, R},
title = {Corrigendum to "Prognostic factors for age-related macular degeneration progression: An overview of systematic reviews" [Surv Ophthalmol 71(3) (2025): 759-773].},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.08.010},
pmid = {42668221},
issn = {1879-3304},
}

@article {pmid42668661,
year = {2026},
author = {Beqiri, S and Herrera, G and Shen, M and Berni, A and El-Mulki, OS and Badla, O and Lam, W and Herrera, E and Ascioti, N and Moxam, J and Shuldiner, S and Boopathiraj, N and Cheng, Y and Le, VH and Trivizki, O and O'Brien, RC and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Symmetry in the Enlargement Rates of Large Hypertransmission Defects between Eyes in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101333},
pmid = {42668661},
issn = {2666-9145},
abstract = {PURPOSE: The symmetry of macular atrophy growth rates between eyes of patients with bilateral nonexudative age-related macular degeneration (AMD) was assessed to determine if both eyes could be used in clinical trials to test therapies that might slow the growth of atrophy.

DESIGN: Retrospective review of prospectively collected swept-source OCT angiography images.

SUBJECTS: Patients with bilateral nonexudative AMD with ≥1 large hypertransmission defect (hyperTD) in both eyes were included.

METHODS: All large hyperTDs, defined by a greatest linear dimension ≥250 μm, were identified by 2 independent graders and annotated using a semiautomated algorithm. Growth rates were assessed using the area, square root (sqrt) area, and the perimeter-adjusted growth-rate strategies. Baseline lesion sizes were stratified using a size breakpoint of 0.9 disc area (DA). Intereye comparisons of annual hyperTD growth rates were performed. Power analyses were calculated to determine the sample sizes needed for different clinical trial designs.

MAIN OUTCOME MEASURES: Intereye concordance of growth rates was evaluated using Lin concordance correlation coefficients, and inter eye growth-rate agreement was evaluated using Bland-Altman analyses. Sample sizes for a 2-arm clinical trial design were calculated to detect a 30% reduction in growth rates in the treatment arm with 80% power and a 2-sided α = 0.05.

RESULTS: Sixty-four subjects (128 eyes) were followed for a mean of 4.2 ± 1.9 years, providing 942 annualized growth-rate intervals. Prior to stratification by baseline size of 0.9 DA, intereye concordance was high (rc = 0.76) for the total area growth rate, but lower for the sqrt and perimeter-adjusted growth rates (rc = 0.51, rc = 0.60, respectively). Upon stratification, lesions <0.9 DA showed low correlation (0.39-0.46) across the 3 growth rates, but lesions ≥0.9 DA showed high correlation regardless of the transformation strategy (0.73-0.78).

CONCLUSIONS: High intereye concordance in hyperTD growth rates was observed for lesions ≥0.9 DA using 3 different growth-rate strategies. Regardless of the growth-rate strategy used, recruitment of fellow eyes in a paired-eye study for localized treatments or both eyes for systemic treatments resulted in a marked reduction in sample sizes, with improved clinical trial efficiency.

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

@article {pmid42668898,
year = {2026},
author = {Kurzawa-Akanbi, M and Haggarty, J and Hansohn, C and Patel, MT and Cree, AJ and Teo, P and Armstrong, M and Coles, N and Platt, M and Griffiths, H and Cordell, HJ and Khundakar, A and Goldberg Oppenheimer, P and Whitfield, P and Lotery, A and Urlaub, H and Mozaffari-Jovin, S and Lako, M},
title = {Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.},
journal = {Journal of extracellular biology},
volume = {5},
number = {9},
pages = {e70178},
pmid = {42668898},
issn = {2768-2811},
abstract = {Vision impairment caused by age-related macular degeneration (AMD) is a global health priority. Retinal pathology is driven by ageing and exacerbated by genetic and environmental risk factors. Peripheral blood circulation is increasingly recognised as a contributor to disease initiation and progression, and a source of biomarkers to support earlier diagnosis and personalised treatment strategies. Here, we performed an analysis of plasma-derived extracellular vesicle (EV)-enriched samples from 30 AMD and 30 controls. Proteomics identified significantly altered proteins in AMD, the majority of which were downregulated with a strong interaction network involving complement proteins and endopeptidase inhibitors. Importantly, many of the altered proteins are known AMD biomarker candidates and act in pathways affecting AMD: oxidative stress response, immune function and proteolysis dysregulation. Lipidomics revealed an increase in total sphingomyelin to ceramide ratio in AMD, indicating lipid metabolism defects. Raman spectroscopy complemented these findings by demonstrating protein and lipid oxidative modifications, alongside compositional abnormalities in AMD samples. Thus, AMD plasma EV-enriched samples carry a systemic signature of complement and coagulation dysregulation, impaired redox homeostasis, and altered sphingolipid metabolism, reflecting established mechanisms of AMD retinal pathology. These AMD-associated biochemical profiles form a promising source for developing new diagnostics and mechanistic insights for precision medicine.},
}

@article {pmid42669558,
year = {2026},
author = {Pavlenko, TA and Chesnokova, NB and Lisovskaya, OA and Beznos, OV and Grigoryev, AV},
title = {Neuroprotective Effect of Subconjunctival Melatonin Injections in 6-Hydroxydopamine-Induced Neurotoxic Eye Damage.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {8},
pages = {1396-1405},
doi = {10.1134/S0006297925603880},
pmid = {42669558},
issn = {1608-3040},
mesh = {Animals ; *Melatonin/administration & dosage/pharmacology/therapeutic use ; Rabbits ; *Neuroprotective Agents/administration & dosage/pharmacology ; *Oxidopamine/toxicity ; Matrix Metalloproteinase 9/metabolism ; Male ; Retina/drug effects/metabolism/pathology ; Vitreous Body/metabolism/drug effects ; alpha-Macroglobulins/metabolism ; Intraocular Pressure/drug effects ; },
abstract = {The search for new effective methods of neuroprotection is relevant for the treatment of a wide range of common eye diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy. Using a rabbit model of neurotoxic eye damage induced by intravitreal injection of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), we studied the effect of subconjunctival injections of 0.1% melatonin solution on pathophysiological and biochemical processes in the eye. Administration of 6-OHDA caused destruction of the retinal pigment epithelium, narrowing of retinal vessels, hemorrhages, decrease in ocular blood flow, and intraocular pressure, as well as reduced activity of α2-macroglobulin and concentrations of matrix metalloproteinase-9 and angiotensin-converting enzyme in the aqueous humor, vitreous body, and retina. Subconjunctival melatonin injections over 9 days resulted in the 2-fold on average reduction of the area of retinal damage, and normalization of the minute volume of ocular blood flow and intraocular pressure. On day 14, an increase in the α2-macroglobulin activity in the aqueous humor (0.66 ± 0.19 vs. 0.49 ± 0.13 nmol/min per 1 mg protein) and vitreous body (0.50 ± 0.15 vs. 0.21 ± 0.07 nmol/min per 1 mg protein, p < 0.05) was observed, along with a decrease in the matrix metalloproteinase-9 concentration (118.4 ± 34.6 vs. 524.3 ± 163.2 ng/mg, p < 0.05) and angiotensin-converting enzyme concentration (371.0 ± 52.1 vs. 596.1 ± 171.5 ng/mg, p < 0.05) in the retina. This indicates reduction in the intensity of inflammation and vascular wall permeability. Melatonin could be considered a promising neuroprotective component in the complex therapy of retinal diseases.},
}

Animals
*Melatonin/administration & dosage/pharmacology/therapeutic use
Rabbits
*Neuroprotective Agents/administration & dosage/pharmacology
*Oxidopamine/toxicity
Matrix Metalloproteinase 9/metabolism
Male
Retina/drug effects/metabolism/pathology
Vitreous Body/metabolism/drug effects
alpha-Macroglobulins/metabolism
Intraocular Pressure/drug effects

@article {pmid42656493,
year = {2026},
author = {Mukwaya, A and Yin, Z and Yarcusko, R and Baldwin, G and Uddin, N and Venkat, H and Xue, Y and Van Arnam, NS and Kam, HT and Chen, DF and Krasemann, S and Lennikov, A and Margeta, MA},
title = {Assessing microglial phagocytosis of apoptotic neurons in vitro: a multimodal approach.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1813556},
pmid = {42656493},
issn = {1662-4548},
support = {R01 EY035312/EY/NEI NIH HHS/United States ; },
abstract = {Microglia are the resident immune cells of the central nervous system, responsible for defending against infections, responding to tissue damage, and maintaining homeostasis. Dysregulation of their phagocytic activity has been implicated in many neurodegenerative diseases of the brain and the eye, including Alzheimer's disease, multiple sclerosis, glaucoma, and age-related macular degeneration. Past work has shown that brain and retinal microglia switch to a disease-associated molecular phenotype (DAM) following phagocytosis of apoptotic neurons in vivo, but it is technically challenging to perform these assessments and isolate phagocytic cells for downstream analysis. Although several protocols exist for isolating and culturing microglia to evaluate their phagocytic activity in vitro, these approaches often fail to mimic the pathophysiology of neurodegeneration, where dysregulated phagocytosis of damaged or apoptotic neurons is a key feature. Here we describe a protocol for evaluating phosphatidylserine-mediated phagocytosis by primary mouse brain microglia in vitro. The procedure involves isolating primary mouse brain microglia, inducing apoptosis in a feeder neuronal cell line, labeling apoptotic cells with a fluorescent dye, feeding the labeled cells to the microglia, and analyzing phagocytosis using several complementary approaches. This protocol enables an accessible and high-throughput assessment of microglial phagocytic activity using a biologically relevant stimulus, offering improved insights into the regulation of this critical immune process in a disease-relevant context.},
}

@article {pmid42657322,
year = {2026},
author = {Shen, LL and Bao, Y and Ying, GS and Keenan, TDL and Chew, EY and Vajzovic, L and Stewart, JM and Del Priore, LV},
title = {A Novel Pixel-Based Spatial Modeling Framework for Mapping At-Risk Retina in Geographic Atrophy Progression.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101330},
pmid = {42657322},
issn = {2666-9145},
support = {P30 EY002162/EY/NEI NIH HHS/United States ; P30 EY026878/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To develop a Pixel-based At-risk Retina Mapping (PARM) framework quantifying local geographic atrophy (GA) progression in nonexudative age-related macular degeneration and evaluate its predictive performance and statistical efficiency relative to conventional area-based measures.

DESIGN: Secondary analysis of a multicenter randomized controlled trial.

PARTICIPANTS: Eyes with GA from the Age-Related Eye Disease Study.

METHODS: Annual color fundus photographs were manually segmented, registered, and converted into 10-μm pixel grids. The perilesional "at-risk" zone was empirically defined as pixels with ≥5% 1-year GA conversion probability. Within this zone, 1-year GA pixel involvement was modeled using a generalized additive model with random effects for eye and participant. Predictors included pixel-level measures (distances to GA border and foveal center) and 9 eye-level factors. Prediction accuracy was evaluated using the area under the receiver operating characteristic curve (AUC). Simulation-based power analyses compared sample size requirements between the PARM framework and conventional area-based measures for detecting a 30% treatment effect (odds ratio 0.70 for pixel conversion) at 80% power (2-sided α = 0.05).

MAIN OUTCOME MEASURES: One-year GA pixel involvement.

RESULTS: We included 239 eyes from 161 participants. Pixels within 500 μm of the GA border had ≥5% 1-year conversion risk, defining the "at-risk" region. Shorter distance to the GA border and greater distance from the foveal center were independently associated with a higher 1-year risk of GA pixel involvement (P < 0.001); 9 eye-level factors did not improve model fit. The pixel-based model achieved an AUC of 0.875 (95% confidence interval [CI], 0.865-0.887), outperforming the eye-level model (AUC = 0.750, 95% CI, 0.740-0.768). Detecting a 30% treatment effect required 30 eyes per arm using the PARM framework, compared with 140 eyes for square-root-transformed area and 310 eyes for total GA area.

CONCLUSIONS: Pixel-based spatial modeling of GA progression within a 500-μm perilesional at-risk zone showed stronger predictive performance than conventional eye-level modeling and improved statistical efficiency relative to area-based measures in internal simulations by leveraging pixel-level distances to the GA border and foveal center. These findings support further evaluation of PARM framework for studying GA progression, with external validation required before clinical-trial implementation.

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

@article {pmid42658802,
year = {2026},
author = {Kim, MS and Nam, S and Lee, J and Woo, SJ},
title = {Risk of intraocular hemorrhage among exudative age-related macular degeneration patients treated with different anti-VEGF agents.},
journal = {PloS one},
volume = {21},
number = {8},
pages = {e0356596},
pmid = {42658802},
issn = {1932-6203},
mesh = {Humans ; Male ; Female ; Ranibizumab/adverse effects/therapeutic use/administration & dosage ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Retrospective Studies ; Recombinant Fusion Proteins/adverse effects/therapeutic use ; Aged ; *Macular Degeneration/drug therapy/complications ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Eye Hemorrhage/epidemiology/chemically induced/etiology ; Middle Aged ; Risk Factors ; Aged, 80 and over ; Vitrectomy ; Republic of Korea/epidemiology ; Proportional Hazards Models ; Intravitreal Injections ; },
abstract = {BACKGROUND: Intraocular hemorrhage is a vision-threatening complication in patients with exudative age-related macular degeneration (AMD) receiving intravitreal anti-vascular endothelial growth factor (VEGF) therapy. We aimed to compare the risk of intraocular hemorrhage requiring vitrectomy among patients with exudative AMD treated with ranibizumab, aflibercept, or brolucizumab.

METHODS AND FINDINGS: This nationwide retrospective cohort study used claims data from the Korean National Health Insurance Review and Assessment Service (May 2014-April 2023). Korean patients aged 40 years or older with newly diagnosed exudative AMD who initiated anti-VEGF therapy and had no history of intraocular hemorrhage were included. The primary outcome was intraocular hemorrhage requiring vitrectomy after anti-VEGF initiation. Time-to-event analyses using Cox proportional hazards regression estimated hazard ratios (HRs) and 95% CIs; Kaplan-Meier curves showed cumulative incidence probability, and logistic regression provided complementary risk estimates. Among 75,812 patients, 1,128 (1.5%) experienced intraocular hemorrhage requiring vitrectomy. Compared with ranibizumab, the adjusted risk was higher with brolucizumab (HR, 1.83; 95% CI, 1.18-2.83; P = .007) and aflibercept (HR, 1.31; 95% CI, 1.14-1.49; P < .001). Logistic regression similarly showed higher odds with aflibercept versus ranibizumab (adjusted odds ratio, 1.32; 95% CI, 1.16-1.51; P < .001). Patients with hemorrhage received fewer anti-VEGF injections in the first year than those without hemorrhage (3.15 ± 1.87 vs 4.01 ± 1.85; P < .001).

CONCLUSION: In this large nationwide cohort, intraocular hemorrhage requiring vitrectomy after anti-VEGF therapy for exudative AMD was rare but occurred more frequently with brolucizumab and aflibercept than with ranibizumab. Although unlikely to be the primary determinant of anti-VEGF selection, these findings provide adjunctive safety information that may be considered when counseling and monitoring selected patients.},
}

Humans
Male
Female
Ranibizumab/adverse effects/therapeutic use/administration & dosage
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
Retrospective Studies
Recombinant Fusion Proteins/adverse effects/therapeutic use
Aged
*Macular Degeneration/drug therapy/complications
*Angiogenesis Inhibitors/adverse effects/therapeutic use
Receptors, Vascular Endothelial Growth Factor/therapeutic use
*Eye Hemorrhage/epidemiology/chemically induced/etiology
Middle Aged
Risk Factors
Aged, 80 and over
Vitrectomy
Republic of Korea/epidemiology
Proportional Hazards Models
Intravitreal Injections

@article {pmid42665201,
year = {2026},
author = {Dhoot, DS and Singerman, LJ and Ferrone, PJ and Wykoff, CC and Goldberg, RA and Guymer, RH and Kim, EL and MacCumber, MW and Maia, A and Yu, S and Yemanyi, F and Coughlin, BA and Baumal, CR and Holz, FG and , },
title = {Early Versus Delayed Pegcetacoplan Treatment for Geographic Atrophy Secondary to Age-Related Macular Degeneration in OAKS, DERBY, and GALE.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.028},
pmid = {42665201},
issn = {1879-1891},
abstract = {PURPOSE: To report the efficacy of early versus delayed pegcetacoplan treatment in eyes with geographic atrophy (GA) secondary to age-related macular degeneration as well as the 48-month safety profile of pegcetacoplan.

DESIGN: Efficacy and safety data from the phase 3 GALE open-label extension (OLE) of the phase 3 OAKS and DERBY studies, representing up to 48 months of continuous pegcetacoplan treatment, were analyzed.

PARTICIPANTS: Eyes with nonsubfoveal or subfoveal GA receiving pegcetacoplan in OAKS and DERBY continued receiving pegcetacoplan at the same dosing regimen in GALE, and sham-observed eyes with nonsubfoveal or subfoveal GA in OAKS and DERBY crossed over to active treatment in GALE at the same dosing interval in those studies.

METHODS: The overall population included eyes with nonsubfoveal GA and eyes with subfoveal GA. Subgroup analyses were performed on data from eyes with nonsubfoveal GA and eyes with subfoveal GA. The early treatment group comprised eyes receiving pegcetacoplan for 48 months across the OAKS, DERBY, and GALE studies. The delayed treatment group included sham-observed eyes from OAKS and DERBY which crossed over at 24 months to receive pegcetacoplan treatment for 24 months in the GALE OLE.

MAIN OUTCOME MEASURES: GA area growth rate, amount of retinal tissue preserved, risk of progression to absolute scotoma, and safety.

RESULTS: In the overall population, 48 continuous months of pegcetacoplan treatment reduced GA area growth rate by up to 24% compared with projected sham, translating to 1.88 mm[2] of retinal tissue. Approximately three times more retinal tissue (up to 3.16 mm[2] with monthly treatment) was preserved in eyes with nonsubfoveal GA in the early treatment group compared with eyes in the nonsubfoveal GA delayed treatment group (1.11 mm[2]). Reduced risk of progression to absolute scotoma of all central 4 and 16 loci (32% and 43%, respectively) was observed in the overall population. GALE safety data were consistent with the findings of the OAKS and DERBY studies.

CONCLUSIONS: Pegcetacoplan demonstrated effectiveness in slowing GA progression and consistent safety over 48 months. Long-term anatomic and functional outcomes support the importance of early treatment to maximize the preservation of retinal tissue and function.},
}

@article {pmid42666667,
year = {2026},
author = {Katan, M and Mróz, K and Pacwa, A and Lewin-Kowalik, J and Smędowski, A},
title = {Gap junction protein connexin 36 proteostatic mechanisms in photoreceptor cells subjected to excitotoxic stress.},
journal = {Acta biochimica Polonica},
volume = {73},
number = {},
pages = {16091},
pmid = {42666667},
issn = {1734-154X},
mesh = {Animals ; *Connexins/metabolism/genetics ; Mice ; Gap Junction delta-2 Protein ; Macrolides/pharmacology ; *N-Methylaspartate/pharmacology ; Proteasome Endopeptidase Complex/metabolism ; Proteotoxic Stress ; *Photoreceptor Cells, Vertebrate/metabolism/drug effects ; Cell Line ; Autophagy/drug effects ; },
abstract = {Connexin 36 (Cx36), a neuronal gap junction protein, is essential for retinal signal transmission but may also contribute to neurodegeneration by facilitating the spread of excitotoxic stress signals. This study aimed to examine the degradation pathway of Cx36 under stress conditions relevant to retinal disease. Using immortalized 661W murine photoreceptor cells transfected with GFP-tagged Cx36, we evaluated the effects of lysosomal inhibition (Bafilomycin A1) and excitotoxic stimulation (NMDA). Immunofluorescence revealed intracellular Cx36 accumulation following Bafilomycin and NMDA exposure, accompanied by increased expression of p62/SQSTM1 and PSMA1, suggesting impaired autophagic flux and a potential compensatory involvement of the proteasome. Elevated RAB11A levels suggested recruitment of endosomal recycling pathways. NMDA treatment was associated with increased ubiquitin accumulation, particularly in Cx36-overexpressing cells, indicating enhanced proteostatic stress under excitotoxic conditions. These findings highlight the stress-responsive behavior of Cx36 and suggest that connexin proteostasis may represent a potential target for future investigation in retinal neurodegeneration, including glaucoma and age-related macular degeneration. Immunofluorescence revealed intracellular accumulation of p62 and PSMA1 after Bafilomycin exposure with signal intensities increasing approximately 1.5-2-fold versus controls (n = 3, p < 0.05). These data are consistent with disrupted autophagic flux and suggest proteasome involvement, but do not constitute functional proof.},
}

Animals
*Connexins/metabolism/genetics
Mice
Gap Junction delta-2 Protein
Macrolides/pharmacology
*N-Methylaspartate/pharmacology
Proteasome Endopeptidase Complex/metabolism
Proteotoxic Stress
*Photoreceptor Cells, Vertebrate/metabolism/drug effects
Cell Line
Autophagy/drug effects

@article {pmid42654271,
year = {2026},
author = {Pieńczykowska, K and Bryl, A and Mrugacz, M},
title = {Obesity and Eye Diseases.},
journal = {Nutrients},
volume = {18},
number = {16},
pages = {},
pmid = {42654271},
issn = {2072-6643},
mesh = {Humans ; *Obesity/complications ; *Eye Diseases/etiology/epidemiology ; Risk Factors ; Macular Degeneration/etiology ; },
abstract = {Background: Obesity has become a major global public health challenge, affecting individuals across all age groups and contributing to a wide range of systemic disorders. Beyond its well-established associations with cardiovascular and metabolic diseases, obesity is increasingly recognized as a chronic inflammatory condition that influences the structure and function of multiple organs, including the eye. Methods: A comprehensive literature review was conducted between November 2025 and June 2026 using PubMed, Web of Science, and Google Scholar. Priority was given to recent studies evaluating the impact of obesity and obesity-related metabolic disturbances on ocular health. Results: Available evidence indicates that obesity is associated with an increased risk of several ophthalmic conditions, including age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, and retinal vein occlusion. Multiple anthropometric measures of adiposity have been positively associated with diabetic retinopathy risk. Although findings regarding glaucoma remain heterogeneous, metabolic syndrome and its components, particularly impaired glucose metabolism, appear to increase glaucoma susceptibility. Obesity has also been linked to dry eye disease through inflammatory and tear film alterations. Conclusions: Obesity exerts significant effects on ocular health through complex metabolic, inflammatory, and vascular pathways. Recognition of obesity as a modifiable risk factor for eye disease may facilitate earlier detection, targeted prevention strategies, and improved multidisciplinary management. Further longitudinal and mechanistic studies are needed to clarify causal relationships and determine whether effective obesity treatment can reduce the burden of vision-threatening ocular disorders.},
}

Humans
*Obesity/complications
*Eye Diseases/etiology/epidemiology
Risk Factors
Macular Degeneration/etiology

@article {pmid42655080,
year = {2026},
author = {Gündüz, A and Ekici Gök, Z and Evren, Ö},
title = {Effects of Intravitreal Anti-VEGF Therapy on Conjunctival Flora and Antibiotic Resistance in Age-Related Macular Degeneration.},
journal = {Microorganisms},
volume = {14},
number = {8},
pages = {},
pmid = {42655080},
issn = {2076-2607},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment among older adults. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents are widely used for neovascular AMD; however, their potential effects on the conjunctival microbiota remain poorly understood. This study evaluated the impact of intravitreal anti-VEGF therapy on conjunctival microbial composition and antimicrobial resistance patterns.

MATERIALS AND METHODS: Ninety patients with AMD were enrolled and assigned to three groups: bevacizumab-treated (n = 30), aflibercept-treated (n = 30), and untreated dry-type AMD controls (n = 30). Conjunctival swab samples were collected two months after the last injection in treated patients and during routine examination in controls. Bacterial identification and antimicrobial susceptibility testing were performed using automated microbiological systems.

RESULTS: Culture positivity rates were comparable among groups, although a lower growth rate was observed in the bevacizumab group (83.3%) than in the aflibercept and control groups (100% each). Staphylococcus epidermidis was significantly more prevalent in both treatment groups than in controls (p = 0.014). Most other bacterial species were detected more frequently in controls. Levofloxacin resistance among staphylococcal isolates was significantly higher in the aflibercept group (p = 0.007), whereas erythromycin and fusidic acid resistance were significantly higher in controls (p = 0.040 and p = 0.001, respectively). Resistance in treated eyes was predominantly associated with S. epidermidis and S. hominis.

CONCLUSIONS: Intravitreal anti-VEGF therapy may be associated with transient alterations in conjunctival microbiota composition and antimicrobial resistance patterns. These findings may have implications for infection prevention in patients undergoing repeated intravitreal injections.},
}

@article {pmid42656281,
year = {2026},
author = {Chun, JM and Choy, S and Seok, JW and Kim, JD and Park, SR},
title = {Photobiomodulation in animal models of ophthalmic disease: protocol for systematic review and meta-analysis of morphological, visual function, and inflammatory outcomes.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1904150},
pmid = {42656281},
issn = {2296-858X},
abstract = {BACKGROUND: Despite accumulating preclinical evidence supporting the therapeutic efficacy of photobiomodulation (PBM) in ophthalmic disease models, the systematic evaluation and quantitative synthesis of these findings remain underexplored. This protocol aims to comprehensively synthesize existing studies by categorizing outcome measures into morphological, visual, and inflammatory domains according to ophthalmic pathology. The primary objective of this study is to evaluate the therapeutic efficacy of PBM for ophthalmic diseases and to consolidate the current body of preclinical evidence.

METHODS: This study will be conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) guidelines. We will include controlled preclinical studies using animal models of four predefined ophthalmic conditions: age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and corneal injury. A systematic search will be conducted across relevant electronic databases without restrictions on publication date. Outcomes will be categorized into three domains, morphological, visual functional, and inflammatory, to evaluate the efficacy of PBM in ophthalmic diseases. Two independent reviewers will perform study selection, data extraction, and risk of bias assessment using the SYRCLE tool. Where appropriate, meta-analyses will be conducted using random-effects models, with heterogeneity assessed using I[2] statistics. Subgroup and sensitivity analyses will be performed to explore sources of variability.

DISCUSSION: This systematic review aims to integrate and assess the quality of current evidence regarding PBM's efficacy across morphological, visual functional, and inflammatory outcomes. Findings will contribute to future trial designs and support the development of standardized protocols for PBM applications in ophthalmology.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251054002, PROSPERO CRD420251054002.},
}

@article {pmid42654113,
year = {2026},
author = {Ma, Z and Zhang, D and Chen, X and Zhang, F},
title = {Kaempferol's Therapeutic Applications and Mechanistic Insights in Ocular Diseases: Current Progress, Challenges, and Translational Opportunities.},
journal = {Pharmaceutics},
volume = {18},
number = {8},
pages = {},
pmid = {42654113},
issn = {1999-4923},
abstract = {Kaempferol is a natural flavonol compound widely present in various single-herb remedies and compound formulations used for the treatment of ocular diseases. Despite its inherent pharmaceutical limitations, accumulating evidence indicates that kaempferol exerts broad protective effects against diverse ocular disorders through multiple biological pathways, highlighting its potential as a multi-target therapeutic candidate in ophthalmology. However, current evidence regarding kaempferol-based ophthalmic applications remains fragmented across different ocular diseases and mechanistic investigations, and a comprehensive evaluation of its therapeutic potential, translational challenges, and existing limitations is still lacking. This review systematically summarizes the research progress on kaempferol in the treatment of eye diseases, encompassing its source distribution, structural characteristics, ocular delivery strategies, disease spectrum coverage, molecular mechanisms, and safety profile. By critically evaluating currently available evidence, this review further identifies unresolved issues and translational barriers that hinder the clinical application of kaempferol in ophthalmology. Regarding delivery strategies, carriers such as gelatin nanoparticles, porous bovine serum albumin membranes, platelet-derived extracellular vesicles, and polyvinylpyrrolidone-based nanocomposites have preliminarily improved ocular surface retention and corneal permeability of kaempferol in models of corneal neovascularization and alkali burns. In terms of therapeutic indications, kaempferol has demonstrated protective effects in diverse experimental models, including age-related macular degeneration (AMD), diabetic retinopathy, diabetic cataract, dry eye disease, fungal keratitis, corneal transplant rejection, acute glaucoma, and retinoblastoma. At the mechanistic level, kaempferol exerts comprehensive pharmacological actions-anti-inflammatory, antioxidant, metabolic regulation, anti-angiogenic, and immunomodulatory-by modulating multiple signaling pathways, including MAPK, NF-κB, STAT1/IRF7, Nrf2/HO-1, VEGF/PI3K/Src/Akt/ERK, aldose reductase, estrogen-related receptor alpha (ERRα), and the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Available safety assessments suggest that kaempferol exhibits a generally favorable safety profile across ocular, cellular, systemic, and genetic evaluations. Despite these advances, the clinical translation of kaempferol in ophthalmology remains limited by insufficient clinical and pharmacokinetic evidence, underdeveloped targeted delivery strategies, and a lack of integrated understanding of its molecular basis in ocular protection. By systematically integrating evidence from ocular disease models, molecular mechanisms, delivery strategies, and safety evaluations, this review bridges fragmented knowledge regarding kaempferol-based ophthalmic applications and provides an integrated framework for understanding its therapeutic potential and translational prospects. Overall, this review highlights kaempferol as a promising multi-target therapeutic candidate for ocular diseases and provides insights into its future translational development.},
}

@article {pmid42642015,
year = {2026},
author = {Chen, X and Han, M and An, Y and Zhang, S and Liu, M and Wang, Y and Zhao, S and Wang, Z and Zhang, Y},
title = {Epigallocatechin gallate protects ARPE-19 cells in vitro and the retina in vivo by suppressing NF-κB p65-mediated ferroptosis.},
journal = {Experimental eye research},
volume = {272},
number = {},
pages = {111214},
doi = {10.1016/j.exer.2026.111214},
pmid = {42642015},
issn = {1096-0007},
abstract = {The accumulation of ferrous ions and resulting oxidative stress within the retinal pigment epithelium triggers ferroptosis, leading to photoreceptor degeneration in dry age-related macular degeneration (dAMD), which is a disease currently without effective therapy. As ferroptosis has been identified as a molecular target of epigallocatechin-3-gallate (EGCG) in other diseases, this study aimed to investigate the protective role of EGCG and its mechanism against ferroptosis in NaIO3-induced ARPE-19 cell and RPE injury. We observed that iron overload disrupts iron homeostasis in both cellular and animal models, leading to RPE damage via ferroptosis activation. In ARPE-19 cells, EGCG attenuated NaIO3-induced injury by reducing Fe[2+], MDA, and LDH levels, increasing GSH content, and upregulating SLC7A11 and GPX4 expression, effects which were equivalent to those produced by Fer-1. Mechanistically, EGCG exerted its anti-ferroptotic effect by binding strongly to NF-κB p65 and inhibiting its activation, consistent with the effects of the NF-κB inhibitor QNZ and NF-κB p65 silencing. In a dAMD model, EGCG administration suppressed ferroptosis, downregulated NF-κB p65 expression, and ameliorated RPE damage. In conclusion, these findings suggest that EGCG alleviates RPE damage associated with NF-κB p65-mediated ferroptosis, providing new insights into AMD pathogenesis and a promising therapeutic strategy.},
}

@article {pmid42642221,
year = {2026},
author = {Jiang, Y and Cheong, KX and Hu, Z and Foo, LL and Zhou, Y and Tang, X and Pan, W and Chen, Z and Saw, SM and Hoang, QV and Yang, Z and Lan, W},
title = {Association between retinal/choroidal vascularity and macular sensitivity in myopic macular degeneration: Aier-SERI high myopia adult cohort study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328323},
pmid = {42642221},
issn = {1468-2079},
abstract = {PURPOSE: To investigate the associations between retinal/choroidal vascular parameters and macular sensitivity (MS) in adults with myopic macular degeneration (MMD).

METHODS: This cross-sectional study included a total of 439 eyes from 253 participants of the Aier-SERI high myopia cohort in Changsha, central China. MS was evaluated using the microperimetry (MP-3). Retinal and choroidal vascular parameters, including superficial vascular density (SVD), deep vascular density (DVD), choriocapillaris perfusion area (CCPA) and choroidal vascularity index (CVI), were quantified using swept-source optical coherence tomography angiography (SS-OCTA). Differences in MS across MMD severity categories were analysed via one-way analysis of variance, and relationships between retinal/choroidal vascular parameters and MS were evaluated using multivariable linear regression models with generalised estimating equations to account for inter-eye correlations.

RESULTS: Participants had an average age of 44.6±6.6 years with a mean spherical equivalent (SE) of -9.1±4.1 D and axial length (AL) of 27.2±1.8 mm. MS, SVD, DVD and CVI in different regions decreased with increasing severity of MMD (all P values <0.05), but CCPA not (p>0.05). In multivariate models, factors related to reduced MS included older age (β=-0.074, p=0.007), longer AL (β=-0.388, p<0.001), increasing severity of MMD (β≤-0.677, all p<0.05), lower SVD (β=0.077, p=0.022), lower DVD (β=0.069, p=0.019) and lower CVI (β=3.083, p=0.015). CVI demonstrated significantly greater discriminatory power for MS impairment compared with SVD and DVD in different regions (all P values <0.05).

CONCLUSION: Reduced MS is associated with more severe MMD, older age, longer AL, lower SVD, lower DVD and lower CVI. Among retinal/choroidal vascular biomarkers, CVI exhibits superior diagnostic utility for identifying MS impairment in MMD, highlighting the choroid's potential role as a sensitive indicator of visual function.},
}

@article {pmid42642671,
year = {2026},
author = {Chang, W},
title = {Early anatomical rescue after switching to aflibercept 8 mg in faricimab-refractory neovascular AMD.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42642671},
issn = {1573-2630},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage/antagonists & inhibitors ; *Recombinant Fusion Proteins/administration & dosage ; Retrospective Studies ; *Visual Acuity ; Female ; *Wet Macular Degeneration/drug therapy/diagnosis ; Intravitreal Injections ; Male ; Angiogenesis Inhibitors/administration & dosage ; Tomography, Optical Coherence/methods ; Aged ; *Drug Substitution ; Fluorescein Angiography/methods ; Follow-Up Studies ; Treatment Outcome ; Dose-Response Relationship, Drug ; Aged, 80 and over ; Time Factors ; *Macula Lutea/pathology ; Fundus Oculi ; Bridge Therapy ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To evaluate early anatomical outcomes after switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD) refractory to faricimab.

METHODS: This retrospective study included 32 eyes of 31 patients with nAMD who were switched from faricimab to aflibercept 8 mg due to persistent or recurrent fluid. Main outcome measures included central subfield thickness (CST), best-corrected visual acuity (BCVA), and proportion of eyes achieving fluid-free macula at weeks 8 and 16. Subgroup analyses were performed based on diagnosis (PCV vs non-PCV) and prior treatment history.

RESULTS: Mean CST decreased significantly from 374.0 ± 88.3 μm at the time of switch to 324.6 ± 80.6 μm at week 8 (p = 0.003) and 321.4 ± 84.0 μm at week 16 (p = 0.002). Fluid-free rate increased from 18.8 to 43.8% at week 8 and 46.9% at week 16. Mean BCVA remained stable throughout. Both PCV (n=12) and non-PCV (n=20) subgroups showed significant CST reduction. Eyes treatment-naïve before faricimab and those treatment-experienced before faricimab demonstrated comparable responses. No serious adverse events were observed.

CONCLUSIONS: Switching to aflibercept 8 mg resulted in rapid and significant anatomical improvement in faricimab-refractory nAMD, with most improvement occurring by week 8. The treatment was effective across diagnostic subtypes including PCV and regardless of prior treatment burden. Although early anatomical improvement was observed, the long-term durability of this response remains unknown and warrants further study.},
}

Humans
*Receptors, Vascular Endothelial Growth Factor/administration & dosage/antagonists & inhibitors
*Recombinant Fusion Proteins/administration & dosage
Retrospective Studies
*Visual Acuity
Female
*Wet Macular Degeneration/drug therapy/diagnosis
Intravitreal Injections
Male
Angiogenesis Inhibitors/administration & dosage
Tomography, Optical Coherence/methods
Aged
*Drug Substitution
Fluorescein Angiography/methods
Follow-Up Studies
Treatment Outcome
Dose-Response Relationship, Drug
Aged, 80 and over
Time Factors
*Macula Lutea/pathology
Fundus Oculi
Bridge Therapy
Middle Aged
Antibodies, Bispecific

@article {pmid42643214,
year = {2026},
author = {Toral, MA and Ng, B and Velez, G and Yang, J and Tsang, SH and Bassuk, AG and Mahajan, VB},
title = {Persistent Cytotoxic Immune Signaling in Anti-VEGF-Treated Neovascular Age-Related Macular Degeneration.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.06.26350115},
pmid = {42643214},
abstract = {PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard of care for neovascular age-related macular degeneration (AMD), yet many patients exhibit persistent retinal degeneration, fibrosis, and incomplete therapeutic response. The molecular pathways underlying this incomplete response remain poorly understood. We sought to identify VEGF-independent signaling pathways active in the vitreous of anti-VEGF-treated AMD patients.

METHODS: We performed multiplex antibody-based proteomic profiling of 1,000 human proteins in vitreous samples from patients with neovascular AMD receiving anti-VEGF therapy (n=8) and comparative controls (n=6). Differential protein expression was assessed using one-way ANOVA, followed by gene ontology and pathway enrichment analyses. Drug-target relationships were evaluated to identify potential opportunities for therapeutic repositioning.

RESULTS: We identified 107 differentially expressed proteins (p<0.05), including key regulators of immune signaling, angiogenesis, and metabolism. Notably, multiple components of cytotoxic lymphocyte pathways were dysregulated, including IL-21R, SIGLEC-7, CTLA4, and IL-2-associated signaling. Enrichment analyses revealed significant activation of pathways related to T-cell activation, interleukin signaling, and leukocyte-mediated cytotoxicity. These immune signatures persisted despite suppression of VEGF signaling. Several clinically available immunomodulatory agents-including abatacept, sirolimus, and dupilumab-targeted pathways identified in this dataset.

CONCLUSIONS: Anti-VEGF-treated neovascular AMD exhibits persistent cytotoxic immune signaling in the vitreous, suggesting that VEGF-independent immune mechanisms may contribute to ongoing retinal damage and incomplete therapeutic response. These findings provide a rationale for combination therapeutic strategies targeting both angiogenic and immune pathways in AMD.},
}

@article {pmid42643435,
year = {2026},
author = {Bellanda, V and Bala, S and Castilho S Barbosa, G and Mohan, N and Schulgit, MJ and Babiuch, AS and Yuan, A and Sastry, A and Talcott, KE and McOwen, D and Igrec, F and Srivastava, SK and Sharma, S and Schachat, AP and Mammo, DA},
title = {Initial Impact of Loss of Copay Assistance From a National Nonprofit Fund on Outcomes of Retinal Disease.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261477369},
pmid = {42643435},
issn = {2474-1272},
abstract = {PURPOSE: Many patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or retinal vein occlusion who have lost copay assistance from the DBA Good Days national charity fund have been forced to switch treatment from branded intravitreal antivascular endothelial growth factor (anti-VEGF) therapy to bevacizumab. This study sought to characterize the short-term impact of these changes on clinical outcomes.

METHODS: This retrospective study included 89 eyes of 69 patients with nAMD, DME, or retinal vein occlusion who transitioned from receiving branded anti-VEGF therapy (aflibercept 2.0 mg or 8.0 mg; faricimab) to bevacizumab. The primary endpoint was changes from baseline in central subfield thickness (CST) after 1, 2, and 3 injections. Secondary endpoints included changes in best-corrected visual acuity (BCVA), intraocular pressure, intraretinal fluid, subretinal fluid, pigment epithelial detachment, injection intervals, predictors of poor outcome (BCVA loss of ≥15 Early Treatment Diabetic Retinopathy Study letters or CST increase of ≥50 µm), and switchback to branded therapy.

RESULTS: From baseline to after the third bevacizumab injection, the CST increased from a mean (±SD) 228.7 ± 52.3 µm to 271.3 ± 40.0 µm in the overall cohort (P = .004), and from 224.1 ± 50.6 µm to 268.6 ± 38.5 µm among nAMD eyes (P = .007). The injection interval decreased from a median 8.6 weeks (interquartile range [IQR], 7.0-10.9 weeks) preswitch to 7.5 weeks (IQR, 5.3-9.5 weeks) after 3 injections (P < .001). Fourteen eyes (15.7%) met the criteria for poor outcome, and 15 (16.9%) were switched back to branded therapy. Worsening intraretinal fluid was an early indicator of suboptimal response, and shorter preswitch injection intervals were a predictor of switching back to branded therapy.

CONCLUSIONS: Switching from branded anti-VEGF therapy to bevacizumab was associated with anatomic worsening and shorter injection intervals. Shorter preswitch intervals and early postswitch intraretinal fluid changes may help identify patients at risk for poor outcomes.},
}

@article {pmid42644681,
year = {2026},
author = {El Majdoubi El Idrissi, K and Pastore, MR and Mehanna, CJ and Miere, A and Souied, EH},
title = {Large Pigment Epithelial Detachments Associated With Type 1 Macular Neovascularization: Do Swept-Source OCT Angiography Devices Detect the Same Thing?.},
journal = {Translational vision science & technology},
volume = {15},
number = {8},
pages = {25},
doi = {10.1167/tvst.15.8.25},
pmid = {42644681},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/instrumentation/methods ; *Retinal Detachment/diagnostic imaging/diagnosis/etiology ; Prospective Studies ; *Fluorescein Angiography/instrumentation/methods ; Female ; Male ; Aged ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Retinal Neovascularization/diagnostic imaging/complications ; Aged, 80 and over ; Sensitivity and Specificity ; },
abstract = {PURPOSE: Large pigment epithelial detachments (PEDs) compromise automated swept-source optical coherence tomography angiography (SS-OCTA) segmentation, leading to false-negative type 1 macular neovascularization (MNV) in neovascular age-related macular degeneration. We compared the diagnostic sensitivity of two SS-OCTA platforms from different generations to assess whether technological advances offset segmentation limitations.

METHODS: This was a prospective comparative study of 82 eyes with type 1 MNV and PED height ≥ 250 µm. Each eye underwent dual SS-OCTA imaging with a first-generation 1050-nm (100-kHz) system and a next-generation 1060-nm (400-kHz) system. Two masked readers evaluated automated versus manually adjusted segmentation slabs across PED height categories.

RESULTS: On the 1050-nm system, detection improved from 22.0% with automated segmentation to 81.7% after manual adjustment (P < 0.001). The 1060-nm system showed higher automated detection (68.3%), with a modest increase to 75.6% after manual segmentation. Stratified analysis showed superior automated performance of the 1060-nm device in shallow PEDs, whereas intermediate PEDs were most challenging for both systems. In very large PEDs, manual segmentation yielded similar detection rates on both devices.

CONCLUSIONS: Detection of type 1 MNV beneath large PEDs is significantly device dependent. Although next-generation SS-OCTA systems improve automated detection, manual segmentation remains crucial for optimal sensitivity and accuracy. Device-specific protocols integrating routine manual review are warranted to avoid false-negative findings and treatment delays.

TRANSLATIONAL RELEVANCE: Manual segmentation remains essential to prevent false-negative detection of type 1 MNV beneath large PEDs, even with next-generation SS-OCTA devices. This has direct implications for diagnostic protocols and treatment decisions in nAMD.},
}

Humans
*Tomography, Optical Coherence/instrumentation/methods
*Retinal Detachment/diagnostic imaging/diagnosis/etiology
Prospective Studies
*Fluorescein Angiography/instrumentation/methods
Female
Male
Aged
*Retinal Pigment Epithelium/pathology/diagnostic imaging
*Retinal Neovascularization/diagnostic imaging/complications
Aged, 80 and over
Sensitivity and Specificity

@article {pmid42648703,
year = {2026},
author = {Huang, RS and Naidu, SC and Mihalache, A and Xie, JS and Popovic, MM and Kertes, PJ and Sarraf, D and Sadda, SR and Muni, RH and Kohly, RP},
title = {Predictors of loss to follow-up in neovascular age-related macular degeneration.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2026.08.006},
pmid = {42648703},
issn = {1715-3360},
abstract = {OBJECTIVE: To investigate the demographic, clinical, and treatment-related risk factors associated with being lost to follow-up (LTFU) among patients with neovascular age-related macular degeneration (nAMD) receiving antivascular endothelial growth factor (anti-VEGF) intravitreal injections (IVIs).

METHODS: We conducted a multicentre retrospective cohort study of patients with nAMD treated with anti-VEGF IVIs in Toronto, Ontario, from January 2012 to December 2021. LTFU was defined as the absence of an ophthalmic visit within 1 year of the last retinal specialist appointment. Univariable and multivariable logistic regression analyses were conducted to examine associations between demographic, clinical, and treatment-related factors and becoming LTFU.

RESULTS: Among 2556 patients with nAMD, 527 (21%) were LTFU over a mean follow-up of 65.5 ± 15.2 months. In multivariable analysis, male sex (OR = 1.40; p < .001), greater travel distance (>200 km; OR = 2.51; p < .001), and multiple systemic comorbidities (≥3; OR = 1.39; p = .01) were associated with higher odds of LTFU. Compared with White patients, Black (OR = 2.07; p < .001) and Hispanic patients (OR = 1.70; p < .001) had increased odds of LTFU. In contrast, age ≥90 years (OR = 0.53; p < .001), worse baseline visual acuity (>20/200; OR = 0.72; p = .03), pseudophakia (OR = 0.80; p = .04), bilateral disease (OR = 0.72; p = .01), and higher first-year anti-VEGF injection burden (OR = 0.55; p < .001) were associated with lower odds of LTFU.

CONCLUSIONS: Male sex, Black or Hispanic race/ethnicity, multiple systemic comorbidities, and greater travel distance were associated with increased odds of becoming LTFU, while older age, worse baseline visual acuity, pseudophakia, bilateral disease, and higher IVI burden were protective factors. These findings can inform the development of targeted retention strategies for high-risk patients.},
}

@article {pmid42649279,
year = {2026},
author = {Ying, Y and Li, R and Huang, J and Hou, J and Huang, P and Chen, M and Wang, J and Huang, A and Wang, J and Chen, K and Gao, X and Liang, H and Deng, Y and Chen, Y and Tian, M and Yu, H and Lai, M and Chi, K},
title = {Association of cardiovascular-kidney-metabolic syndrome with blinding eye diseases: insights from a UK Biobank cohort analysis.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42649279},
issn = {1476-5454},
support = {U24A20707, 82271125, 82301260, 82301205//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2024T170185//China Postdoctoral Science Foundation/ ; },
abstract = {BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome's overall impact on major blinding eye diseases remains unclear.

METHODS: We included participants from the UK Biobank. Baseline CKM syndrome at study entry was classified into five stages according to the American Heart Association criteria. We calculated the absolute incidence rates of cataract, glaucoma, and age-related macular degeneration (AMD) across CKM stages. The associations between CKM syndrome and these eye diseases were examined using Cox proportional hazards models, with further sensitivity and subgroup analyses conducted to assess robustness.

RESULTS: During more than 10 years of follow-up, 50,894 cataract events, 11,518 glaucoma events, and 8708 AMD events were documented. The absolute incidence rates of cataract, glaucoma, and AMD differed across baseline CKM stages, with the highest rates observed at stage 3. Compared with stage 0, stage 3 CKM syndrome demonstrated the largest effect size estimates for cataract (HR 2.25 [95% CI 2.10-2.41]), glaucoma (HR 1.76 [1.51-2.05]), and AMD (HR 2.08 [1.76-2.46]).

CONCLUSIONS: Baseline CKM syndrome was closely associated with the risk of major blinding eye diseases.},
}

@article {pmid42650298,
year = {2026},
author = {Toro, MD and Avitabile, A and Amato, R and Rusciano, D and Gagliano, C},
title = {Photobiomodulation for Photoreceptor Rescue in Retinal Disease: Mitochondrial, Redox, Vascular, and Translational Perspectives-A Narrative Review.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/antiox15081034},
pmid = {42650298},
issn = {2076-3921},
abstract = {Photoreceptors work in a biologically demanding compartment of the eye. They consume large amounts of energy, receive continuous light and oxygen, and renew outer-segment membranes enriched in polyunsaturated lipids. These conditions are necessary for vision, but they also make the outer retina poorly tolerant to persistent mitochondrial dysfunction and oxidative stress. Photobiomodulation (PBM), mainly based on red and near-infrared light, has been investigated as a way to support retinal cells that are functionally impaired but not yet irreversibly lost. The field has also acquired new clinical relevance after the 2024 De Novo marketing authorization by the United States Food and Drug Administration (FDA) of the Valeda Light Delivery System for dry age-related macular degeneration (AMD). This narrative review examines the mitochondrial, redox, inflammatory, and neurovascular mechanisms proposed for PBM, and discusses preclinical and clinical evidence across nonexudative AMD, inherited retinal degeneration, diabetic retinal disease, and light-induced damage. Current findings are encouraging, but devices, doses, schedules, endpoints, and sponsorship patterns differ substantially among studies. PBM therefore deserves further investigation, especially in early or intermediate disease, but its clinical use should remain linked to tested protocols, rigorous safety monitoring, and biomarkers of residual retinal functional reserve.},
}

@article {pmid42652099,
year = {2026},
author = {Zeng, J and Zhang, J and Schulz, J and Arafah, ADB and Lee, S and Yam, M and Shen, Y and Zhou, F and Zhang, T and Gillies, MC and Zhu, L},
title = {Region-Specific Proteomic Profiles of Extracellular Vesicles (EVs) Derived from Human Macular and Peripheral RPE-Choroid Explants.},
journal = {Biomedicines},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/biomedicines14081715},
pmid = {42652099},
issn = {2227-9059},
support = {N/A//Sydney Nano Institute Kickstarter funding/ ; GNT2020950//National Health and Medical Research Council/ ; GNT1195021//National Health and Medical Research Council/ ; DE230100837//Australian Research Council/ ; },
abstract = {Background: Regional heterogeneity of the macula and peripheral retinas contributes to the differences in retinal physiology, metabolic demand and susceptibility to macular diseases such as age-related macular degeneration (AMD), diabetic macular oedema (DME) and Macular telangiectasia type 2 (MacTel). Extracellular vesicles (EVs) released from the retinal pigment epithelium (RPE)-choroid are increasingly recognised as mediators of extracellular communication and correlate with the molecular biological states of their tissue of origin. However, regional variation in EV composition in human RPE-Choroid tissues remains poorly characterised. Methods: Human macular and peripheral RPE-choroid explants from non-diseased donor eyes (n = 4) were cultured ex vivo using a transwell system. EV and EV-depleted conditioned media were collected by differential ultracentrifugation, respectively. EVs were characterised by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Proteomic profiling was performed using LC-MS/MS followed by multivariate, pathway, and differential expression analyses. Results: TEM and NTA confirmed the presence of vesicle-like particles in a 119-140 nm size range, indicating small EVs in both regions. Proteomic analysis demonstrated a region-associated separation between the macular and peripheral samples in both EV proteome and EV-depleted soluble secretome datasets. GO enrichment analysis revealed that macular EV proteomes were enriched for wound healing, cell-substrate adhesion, and focal adhesion-related terms with a high abundance of integrin and annexin family members, whereas peripheral EV proteomes were enriched for retinoid- and vitamin-binding terms. In the EV-depleted soluble secretome, macular-enriched proteins were associated with actin binding and extracellular matrix-related terms, while peripheral-enriched proteins were correlated with RNA localisation and nuclear compartment terms. Comparative analysis identified EV-specific, secretome-specific, and shared extracellular protein pools. Several EV-specific markers and membrane proteins such as annexins and integrins, showed a relatively high enrichment in macular EV proteomes, whereas CD63 is more abundant in peripheral EV proteomes. In contrast, EV-depleted soluble secretome contains cytokine- and ligand-associated proteins, including MIF, SPP1, and IL6, which may suggest that EVs and soluble secreted proteins represent partially distinct extracellular signalling compartments. Conclusions: Human macular and peripheral RPE-choroid explants released secretory proteins in a regional differentiated manner, supported by PLS-DA and GO enrichment analyses of both EV proteomes and EV-depleted soluble secretome. Further analysis of the EV proteomes may show that such differences were also able to be reflected in protein categories such as EV-specific markers, mitochondrial and membrane proteins. These findings provide a foundation for future investigations into the role of EV-mediated communication in macular diseases and may support the development of region-specific extracellular biomarkers and therapeutic targets.},
}

@article {pmid42652191,
year = {2026},
author = {Chong, V},
title = {The Biochemical and Genetic Architecture of Geographic Atrophy: The Role of the FHL-1/CFH Axis and the Paradigm of RNA Interference Therapeutics.},
journal = {Biomedicines},
volume = {14},
number = {8},
pages = {},
doi = {10.3390/biomedicines14081809},
pmid = {42652191},
issn = {2227-9059},
abstract = {Geographic atrophy (GA) represents the advanced, non-neovascular (dry) form of age-related macular degeneration (AMD), a chronic, progressive, and currently irreversible neurodegenerative disease of the retina. The clinical consequences of GA are severe; it is characterized by the insidious, expanding loss of the retinal pigment epithelium (RPE), the overlying photoreceptors, and the underlying choriocapillaris. This state of complete RPE and outer retinal atrophy (cRORA) permanently destroys the neural architecture required for high-acuity central vision. For decades, the pathophysiological etiology of geographic atrophy was framed principally in terms of cumulative oxidative stress, lipid peroxidation, and cellular senescence. However, the foundational understanding of AMD pathophysiology changed substantially following the landmark genomic discoveries published in 2005. Multiple independent genome-wide association studies (GWAS) linked specific single-nucleotide polymorphisms in the CFH gene to a substantially increased risk of developing AMD. The CFH gene encodes Complement Factor H (FH) and its alternative splice variant, Factor H-like protein 1 (FHL-1), which are the primary soluble regulators of the alternative complement pathway. This genetic discovery established GA not merely as a disease of metabolic wear-and-tear, but fundamentally as an immunologic disorder driven by the chronic dysregulation of the innate immune system. With the rapid emergence and clinical validation of targeted gene-silencing technologies, particularly small interfering RNA (siRNA) and antisense oligonucleotides, there is substantial scientific and pharmaceutical interest in modulating the complement cascade at the post-transcriptional level. This narrative review examines the structural biology, spatial partitioning, and pathophysiological roles of the FHL-1/CFH axis in GA focusing on the possibilities of using siRNA as a new potential therapy for GA.},
}

@article {pmid42652879,
year = {2026},
author = {Eggarter, V and Ruscitti, L and Ascioti, N and Bonanata, M and Peyla, A and Simona, F and Menghini, M and Grimaldi, G},
title = {Artificial Intelligence-Assisted Analysis of Retinal Pigment Epithelium Tears in Patients with Neovascular Age-Related Macular Degeneration Treated with Aflibercept (2 mg and 8 mg) and Faricimab: A Single-Centre Retrospective Case Series.},
journal = {Journal of clinical medicine},
volume = {15},
number = {16},
pages = {},
doi = {10.3390/jcm15166478},
pmid = {42652879},
issn = {2077-0383},
abstract = {Purpose: We aimed to describe retinal pigment epithelium (RPE) tears in patients with neovascular age-related macular degeneration (AMD) and pigment epithelial detachment (PED), focusing on OCT features and AI-assisted image analysis. Methods: This retrospective case series included patients with neovascular AMD and PED who developed RPE tears between 2020 and 2025 after treatment with intravitreal aflibercept (2 mg or 8 mg) or faricimab. Multimodal imaging, including spectral-domain OCT and infrared imaging, was reviewed. PED morphology, fluid characteristics, RPE denudation, timing of RPE tear, and visual outcomes were analyzed using manual grading and AI-assisted software. Results: Among 375 PED-bearing eyes, 11 eyes of 11 patients developed an RPE tear (2.9%), of which 10 (90.9%) were temporally associated with anti-VEGF treatment. Rates were similar across agents-2.7% (aflibercept 2 mg), 3.0% (aflibercept 8 mg) and 2.4% (faricimab)-with no significant difference. Eight eyes (72.7%) were treatment-naïve and one tear (9.1%) occurred spontaneously after hemorrhage without recent injection. Among treatment-associated tears, 30% followed the first and 50% the second injection (mean 2.1 injections), detected a mean of 44 ± 30 days after the last injection. Mean baseline PED height was 594.8 ± 239.2 μm and median AI-derived PED volume was 2922 nL. Mean RPE-denudation area at detection was 5.25 ± 3.87 mm[2], remaining stable in 7 of 9 evaluable eyes. Visual acuity was stable or improved in seven eyes; four lost ≥15 ETDRS letters. Conclusions: RPE tears were an uncommon, predominantly early complication occurring in eyes with large PEDs, with no excess risk from second-generation agents. AI-assisted OCT may aid anatomical characterisation, and most eyes retained vision with continued therapy.},
}

@article {pmid42652894,
year = {2026},
author = {Macha, N and Yu, M},
title = {Full-Field Stimulus Threshold: A Key Functional Outcome Measure in Retinal Diseases and Clinical Trials.},
journal = {Journal of clinical medicine},
volume = {15},
number = {16},
pages = {},
doi = {10.3390/jcm15166492},
pmid = {42652894},
issn = {2077-0383},
support = {EY025585/EY/NEI NIH HHS/United States ; },
abstract = {Full-field stimulus threshold (FST) testing is a psychophysical method used to assess global retinal function, particularly in patients with severe visual impairment where conventional perimetry is unreliable. This review explores the development, clinical protocols, and applications of FST in retinal diseases, with a focus on its role in inherited retinal dystrophies (IRDs) such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). FST has emerged as a key functional outcome measure in clinical trials, particularly in evaluating novel gene therapies for IRDs. Its fixation-independent nature and ability to detect residual visual function make it valuable for assessing disease progression and treatment efficacy. However, challenges remain regarding standardization and test variability. Ongoing efforts seek to standardize and optimize FST protocols and establish it as a standardized metric in both clinical and research settings.},
}

@article {pmid42653456,
year = {2026},
author = {Song, YS and Wang, S and Darjatmoko, SR and Sheibani, N and Sorenson, CM},
title = {Bcl-2-Dependent Persistence of Mononuclear Phagocytes Promotes Ocular Fibrosis.},
journal = {International journal of molecular sciences},
volume = {27},
number = {16},
pages = {},
doi = {10.3390/ijms27167455},
pmid = {42653456},
issn = {1422-0067},
support = {Unrestricted award to the Department of Ophthalmology and Visual Sciences//Research to Prevent Blindness/ ; Endoument Funds//Retina Research Foundation/ ; AMD Research Award//Edward N. & Della L. Thome Memorial Foundation/ ; AMD Research Award//Carl Marshall and Mildred Almen Reeves Foundation/ ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; },
mesh = {Animals ; Mice ; Fibrosis ; *Proto-Oncogene Proteins c-bcl-2/metabolism/genetics ; *Choroidal Neovascularization/pathology/metabolism/etiology ; Macrophages/metabolism/pathology ; Disease Models, Animal ; *Phagocytes/metabolism/pathology ; Mice, Inbred C57BL ; },
abstract = {Ocular diseases, such as neovascular age-related macular degeneration (nAMD) and proliferative vitreoretinopathy (PVR), have a fibrotic component that negatively impacts vision. Unfortunately, few treatments are available to mitigate fibrosis in the eye. The clearance of inflammatory cells proceeds, at least in part, through the intrinsic cell death pathway in which Bcl-2 family members play integral roles. Here, we assessed the influence of Bcl-2 expression in mononuclear phagocytes (MP) on the engagement and clearance of inflammatory cells, choroidal neovascularization (CNV), and subsequent subretinal fibrosis in a mouse laser-induced CNV model. Lack of Bcl-2 expression in MP (Bcl-2[MP] mice) decreased neutrophil (Gr1[+]) and microglia (Iba1[+]) presence without impacting M1 (CD80[+]) and M2 (CD206[+]) macrophage presence, CNV, or fibrosis during the first 2 weeks following laser photocoagulation. Later, after inflammation dampens, decreased later-stage fibrosis and CNV were noted in Bcl-2[MP] mice, which were accompanied by increased presence of M2 macrophages (CD206[+]). However, how these increased levels of CD206[+] M2 macrophages in the absence of Bcl-2 contribute to decreased CNV and fibrosis remains unknown. To address whether Bcl-2 expression affects other forms of ocular fibrosis, we utilized the dispase PVR model. Bcl-2[MP] mice, or treatment of wild-type mice with Bcl-2 inhibitors, significantly decreased fibrosis in the PVR model. Furthermore, Bcl-2 inhibitors mitigated CNV and fibrosis (collagen I-defined) in wild-type mice during laser photocoagulation. Thus, inhibition of Bcl-2 activity prevents the late-stage clearance of CD206[+] M2 macrophages during nAMD and PVR, mitigating ocular neovascularization and fibrosis.},
}

Animals
Mice
Fibrosis
*Proto-Oncogene Proteins c-bcl-2/metabolism/genetics
*Choroidal Neovascularization/pathology/metabolism/etiology
Macrophages/metabolism/pathology
Disease Models, Animal
*Phagocytes/metabolism/pathology
Mice, Inbred C57BL

@article {pmid42653812,
year = {2026},
author = {Panos, GD},
title = {Faricimab 6 mg Versus Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Protocol-Standardised In Silico Study.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {8},
pages = {},
doi = {10.3390/ph19081316},
pmid = {42653812},
issn = {1424-8247},
abstract = {Background: Faricimab 6 mg and aflibercept 8 mg permit extended treatment intervals in neovascular age-related macular degeneration (nAMD), but their pivotal programmes used different loading and maintenance schedules. This study compared treatment burden under the same loading and treat-and-extend protocol and included an exploratory longitudinal analysis of published aggregate visual and anatomical outcomes. Methods: Treatment-specific Dirichlet distributions represented persistent Q8W, Q12W and Q16W capability. Both treatments received injections at weeks 0, 4, 8 and 16, followed by identical four-week extensions from Q8W to Q16W. The primary analysis comprised 30,000 evidence draws, 100,000 paired virtual eyes, a 1.5-million-pair scenario grid and a nested five-million-pair probabilistic analysis. Exploratory multilevel meta-regressions estimated BCVA and change in retinal thickness through week 52; IRF, SRF and complete retinal dryness were analysed separately. Results: Mean injections with faricimab and aflibercept 8 mg were 7.255 and 7.212 at week 52 and 11.522 and 11.144 at week 104. The nested 104-week difference was -0.393 injection (95% uncertainty interval -0.682 to -0.107), but broad source-weight uncertainty included no difference and credible source analyses changed the direction of the contrast. Exploratory week-52 BCVA gains were 5.65 and 6.29 letters, respectively; the difference was 0.64 letter (95% uncertainty interval -1.41 to 2.70) and should be interpreted in the context of three aflibercept 8 mg study families. The expanded retinal-thickness sensitivity model estimated changes of -171.8 and -147.2 micrometres, while the between-treatment direction varied in the three-dose-only analysis. Complete retinal dryness was projected in 57.0% and 69.0% of eyes, respectively, based on three study families per treatment. Conclusions: Use of the same protocol predicted essentially equal one-year burden and a small two-year fixed-weight difference that varied across source choices. The exploratory longitudinal projections, informed by three independent aflibercept 8 mg study families at one year, provide supportive context for the visual and anatomical findings but should be interpreted as hypothesis-generating rather than confirmatory.},
}

@article {pmid42640665,
year = {2026},
author = {Hung, CH and Chang, TW},
title = {Comment on: "Impact of GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus on the Development and Progression of Age-Related Macular Degeneration".},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004994},
pmid = {42640665},
issn = {1539-2864},
}

@article {pmid42640689,
year = {2026},
author = {Fragiotta, S and Freund, KB and Fernández-Avellaneda, P and Liakopoulos, S and Bijon, J and Moraes, RT and Dolz-Marco, R},
title = {Retinal pigment epithelium defects, sealed and unsealed: a lifecycle and disease agnostic terminology.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004991},
pmid = {42640689},
issn = {1539-2864},
abstract = {PURPOSE: To describe two recurrent phenotypes of retinal pigment epithelium (RPE) defects, sealed and unsealed, which may occur in various diseases.

METHODS: Medical records and multimodal imaging of 17 patients (70.3 ± 9.3 years) with RPE defects, including RPE apertures, RPE detachment (RPED) devoid of RPE, and serous maculopathy with the absence of RPE (SMARPE), were retrospectively analyzed. Proposed pathogenic mechanisms are presented, revising current terminology.

RESULTS: Eyes with RPE apertures (12/17, 70.6%) and SMARPE (1/17, 5.9%) presented RPE defects connecting the subretinal and sub-RPE spaces with subretinal fluid (SRF) and intact outer retina. These features are consistent with patent RPE defects, termed 'unsealed'. RPED devoid of RPE defects developed in ¾ eyes (75%) over a serous PED without collapse. The lesions occurred beneath a degenerated outer retina that adheres to the RPE defect without SRF, supporting the term 'sealed'.

CONCLUSIONS: RPE defects beneath a disrupted photoreceptor layer may become "sealed" by reactive Müller cell gliosis, preventing the occurrence of SRF. RPE defects with intact photoreceptors remain "unsealed", resulting in SRF accumulation. We propose "sealed" and "unsealed" as disease agnostic terms, which can be used for cases previously described as "RPE aperture," "SMARPE," and "RPED devoid of RPE".},
}

@article {pmid42640691,
year = {2026},
author = {Kazantzis, D and Thottarath, S and Sheemar, A and Keskin, AM and Kubravi, HS and Sivaprasad, S and , },
title = {Incidence and associations of Retinal pigment epithelial (RPE) tear post-loading phase of aflibercept 2mg in Treatment Naïve Neovascular Age-Related Macular Degeneration (nAMD): PRECISE study report 10.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004985},
pmid = {42640691},
issn = {1539-2864},
abstract = {PURPOSE: To report the incidence of retinal pigment epithelial (RPE) tears following three monthly 2-mg aflibercept injections in treatment-naïve neovascular age-related macular degeneration (nAMD) and to identify associated risk factors.

METHODS: Treatment-naïve patients aged ≥50 years with nAMD and baseline visual acuity (VA) between 24 and 78 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters were included. RPE tears were diagnosed on optical coherence tomography (OCT) as a definite discontinuity of the RPE. Logistic regression using Generalized Estimating Equations (GEE) was performed to account for correlated eye data and identify factors associated with RPE tear development. Cluster bootstrap receiver operating characteristic (ROC) curve analysis assessed the predictive value of baseline pigment epithelial detachment (PED) height.

RESULTS: A total of 1,929 eyes were analyzed; 67 eyes (3.5%) developed an RPE tear after the aflibercept loading phase. Multivariable analysis adjusted for age, ethnicity, and sex showed that male sex, poorer baseline VA, increased central subfield thickness, hemorrhagic PED, increased PED height, presence of subretinal hyperreflective material (SHRM), and polypoidal choroidal vasculopathy (PCV) were associated with higher odds of RPE tear and that presence of drusen with decreased odds of RPE tear. ROC analysis demonstrated that a baseline PED height of 244 µm optimally predicted RPE tear development with a sensitivity of 73.8% and a specificity of 73.6%.

CONCLUSION: RPE tears occurred in 3.5% of treatment-naïve nAMD eyes after aflibercept loading phase. Several baseline clinical and imaging risk factors were identified to be significantly associated with RPE tear development.},
}

@article {pmid42640898,
year = {2026},
author = {Fan, Z and Qin, Y and Chen, L and Yuan, J and Xiong, Z and Chen, X and Lai, S and Tham, YC and Sheng, B and Wang, X and Grzybowski, A and Lee, AY and Lee, CS and Cheung, CY and Liu, TYA and Wong, TY and Wang, YX},
title = {A decade of artificial intelligence research in ophthalmology: Global trends and transferable insights for medical AI.},
journal = {PLOS digital health},
volume = {5},
number = {8},
pages = {e0001347},
pmid = {42640898},
issn = {2767-3170},
abstract = {To characterize global trends in ophthalmic AI research from 2015-2025 and drive transferable insights into the broader evolution of AI in medicine, we conducted a systematic bibliometric analysis of original AI articles in ophthalmology indexed in the Web of Science Core Collection, Scopus, and Pubmed from 2015 to 2025. Publications were screened and categorized using an LLM-assisted pipeline with predefined labels, and agreement between LLM-assisted classifications and human grading was evaluated. We analyzed temporal trends and emergence patterns across study design, model architecture, disease focus, and data modalities. Among 12,911 included articles, annual publications increased at a compound annual growth rate of 39.7%, from 108 in 2015-3061 in 2025. Four key shifts were identified. Study design: Development studies (88.3%) dominated through the period, whereas evaluation studies (7.4%) began to emerge in 2019. Model architecture: Classical deep learning (71.8%) became the most prevailing approach from 2017, while foundation model studies (0.6%) increased sharply in 2024-2025. Disease focus: Diabetic retinopathy (32.9%), glaucoma (17.5%), and age-related macular degeneration (12.6%) remained the leading disease areas, while corneal diseases (7.0%), cataract (4.3%) and myopia (3.4%) emerged after 2019-2020 and grew rapidly. Data modalities: Among image-based modalities (84.1%), color fundus photography and retinal optical coherence tomography remained dominant but plateaued after 2019, whereas text-based modalities (5.5%) continued to rise after 2022. Over the past decade, ophthalmic AI research expanded rapidly and evolved from narrow image-based deep learning toward broader work spanning evaluation studies, foundation models, multimodal data integration, and a wider spectrum of eye diseases. These trajectories may extend beyond ophthalmology, offering broader insights into how medical AI matures toward clinical evaluation and translation.},
}

@article {pmid42641479,
year = {2026},
author = {Giulivi, C and Villafuerte-Trisolini, C and Greenblatt, ZL and Dang, J and Tork, A and Mullah, R and Le, S and Min, A and Nair, M and Vorkapich, A and Tran, HA and Doyle, E and Law, A and O'Keefe, O and Wu, A and Shibata, B and Ripolles-Garcia, A and Thomasy, SM and Harris, RA and Chen, R and Liu, YA and Yiu, G},
title = {Adaptive and degenerative mitochondrial remodeling define distinct redox states in age-related macular degeneration.},
journal = {Redox biology},
volume = {96},
number = {},
pages = {104365},
doi = {10.1016/j.redox.2026.104365},
pmid = {42641479},
issn = {2213-2317},
abstract = {Age-related macular degeneration (AMD) is associated with mitochondrial dysfunction and oxidative stress, yet the relationship between mitochondrial remodeling, redox homeostasis, and disease progression remains poorly understood. Nonhuman primates (NHPs) develop spontaneous AMD-related phenotypes, including punctate deposits and soft drusen, providing a unique animal model to investigate mitochondrial pathology in the aging retinal pigment epithelium (RPE). We integrated quantitative mitochondrial ultrastructural profiling with flavoprotein fluorescence imaging, plasma metabolomics, and whole-exome sequencing to characterize mitochondrial and redox alterations in aged rhesus macaques with AMD-related lesions. Flavoprotein fluorescence imaging demonstrated increased metabolic heterogeneity in eyes with soft drusen, consistent with altered mitochondrial redox states and oxidative stress. Morphometric analysis identified distinct mitochondrial remodeling patterns across phenotypes. Normal aging was characterized by concentric cristae and type I paracrystalline inclusions. Eyes with punctate deposits exhibited increased mitochondrial fusion-associated morphology, hyperbranching, and type I paracrystalline inclusions, consistent with a stress-responsive mitochondrial remodeling pattern. In contrast, eyes with soft drusen exhibited reduced fusion-associated morphology, reduced structural complexity, and ultrastructural features consistent with mitochondrial deterioration. These ultrastructural patterns were accompanied by distinct plasma metabolomic signatures. Punctate deposits were associated with altered glycolytic, tricarboxylic acid cycle, and redox-buffering metabolites, consistent with differences in stress-responsive metabolism, whereas soft drusen exhibited metabolomic signatures consistent with altered redox homeostasis. Whole-exome sequencing identified a mitochondrial DNA variant, MT:9582G > A, in cytochrome c oxidase subunit III (COX3) associated with the drusen phenotype. Collectively, these findings identify distinct mitochondrial remodeling patterns associated with AMD-related phenotypes in aged rhesus macaques. The convergence of ultrastructural, imaging, metabolomic, and genetic analyses suggests that punctate deposits and soft drusen are associated with different mitochondrial and redox-related responses to chronic retinal stress. These findings provide a framework for future studies investigating mitochondrial biology and redox-driven mechanisms in AMD.},
}

@article {pmid42633835,
year = {2026},
author = {Viggiano, P and Pignataro, MG and Termite, AC and Boscia, G and Savastano, A and Evangelista, F and Alessio, G and Boscia, F and Peto, T and Chakravarthy, U},
title = {Retinal Pigment Epithelial Detachment: Molecular Mechanisms, Multimodal Imaging Classification, and Clinical Management Across the Spectrum of Macular Disease.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101512},
doi = {10.1016/j.preteyeres.2026.101512},
pmid = {42633835},
issn = {1873-1635},
abstract = {Pigment epithelial detachment (PED) represents a critical structural finding across the spectrum of chorioretinal diseases, occurring in 63-80% of eyes with neovascular age-related macular degeneration and frequently in central serous chorioretinopathy, polypoidal choroidal vasculopathy, and inflammatory conditions. This review provides a comprehensive analysis of current multimodal imaging techniques in the diagnosis and management of PEDs. We examine the role of various imaging modalities including optical coherence tomography (OCT), OCT angiography (OCTA), en face OCT, fluorescein angiography (FA), indocyanine green angiography (ICGA), infrared imaging (IR), and fundus autofluorescence (FAF) in evaluating PEDs. Each imaging modality provides unique insights: OCT reveals characteristic structural changes and quantitative biomarkers (height, volume, prechoroidal cleft); OCTA demonstrates type 1-4 MNV localisation; en face OCT visualises internal architecture; FA shows leakage patterns; ICGA identifies choroidal hyperpermeability; IR assists RPE evaluation; and FAF highlights dysfunction patterns. The integration of these imaging techniques has enhanced our understanding of PED pathophysiology-hydrostatic imbalance, RPE pump failure, Bruch's alterations-and improved classification into drusenoid, serous, fibrovascular, and haemorrhagic subtypes. This review particularly emphasises how advanced OCT/OCTA has advanced our knowledge of PED natural history, treatment response (anti-VEGF/PDT), and complications (RPE tears). We also discuss future directions in AI-driven classification and imaging biomarkers for personalised therapeutic approaches. The synergistic use of multimodal imaging represents a cornerstone in PED management, enabling precise diagnosis, risk stratification, and tailored treatment strategies.},
}

@article {pmid42635473,
year = {2026},
author = {Pilotto, E and Parolini, F and Edwards, MM and Midena, E and Midena, G},
title = {Hyperreflective Choroidal Foci Characterization Supports the Existence of Different Clinical Phenotypes of Geographic Atrophy.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {56},
doi = {10.1167/iovs.67.10.56},
pmid = {42635473},
issn = {1552-5783},
mesh = {Humans ; *Geographic Atrophy/diagnosis/pathology ; Tomography, Optical Coherence/methods ; *Choroid/pathology ; Phenotype ; Female ; Retinal Pigment Epithelium/pathology ; Aged ; Male ; Fluorescein Angiography/methods ; Aged, 80 and over ; },
abstract = {PURPOSE: To characterize and quantify optical coherence tomography (OCT) hyperreflective choroidal foci (HCF) in geographic atrophy (GA) of age-related macular degeneration (AMD) and to assess their distribution across different GA phenotypes.

METHODS: Eyes with bilateral GA (B-GA) or unilateral GA (U-GA) with macular neovascularization in the fellow eye, as well as controls, were included. HCF were classified in different subtypes according to size (small, ≤30 µm; large, >30 µm) and reflectivity (high or intermediate). Each subtype was also identified according to location (choriocapillaris vs. choroid). HCF counts were quantified within complete retinal pigment epithelium and outer retinal atrophy (cRORA), incomplete retinal pigment epithelium and outer retinal atrophy (iRORA), and non-atrophic outer retinal alteration (noRORA). The comparison of HCF count between the GA groups and the controls was performed only in noRORA segments.

RESULTS: Seventy-seven eyes were enrolled (40 B-GA, 18 U-GA, and 19 controls). The extent of cRORA, iRORA, and noRORA regions did not differ between the two GA groups (P > 0.05 for all). In noRORA regions, both GA groups exhibited significantly higher HCF number compared to controls (P < 0.0001 for both). Total HCF count did not differ between the GA groups across all RORA regions (P > 0.05 for all). However, the analysis of HCF subtypes revealed significant differences. Small intermediate-reflectivity choriocapillaris HCF were significantly more numerous in U-GA eyes than in B-GA in cRORA and noRORA regions (P = 0.0006 and P = 0.006, respectively). Large high-reflectivity choriocapillaris HCF were significantly more numerous in B-GA eyes than in U-GA within cRORA regions (P = 0.025). In choroid, HCF subtypes did not differ between the two GA groups in the different RORA regions.

CONCLUSIONS: Although overall HCF burden was similar between the two GA phenotypes, significant distinct distribution of HCF subtypes was documented. Detailed HCF characterization provides new insights into GA heterogeneity, supporting the value of novel biomarkers in further characterizing different GA phenotypes.},
}

Humans
*Geographic Atrophy/diagnosis/pathology
Tomography, Optical Coherence/methods
*Choroid/pathology
Phenotype
Female
Retinal Pigment Epithelium/pathology
Aged
Male
Fluorescein Angiography/methods
Aged, 80 and over

@article {pmid42636089,
year = {2026},
author = {Sabaner, MC and Gunes, I and Anguita, R and van Dijk, EHC and Ferro Desideri, L and Cehofski, LJ and Ramtohul, P and Subhi, Y},
title = {Concurrent macular neovascularization in shallow irregular retinal pigment epithelium elevation phenotypes in age-related macular degeneration and chronic central serous chorioretinopathy: A systematic review and meta-analysis.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70226},
pmid = {42636089},
issn = {1755-3768},
support = {//Türkiye Bilimsel ve Teknolojik Araştırma Kurumu/ ; },
abstract = {This systematic review and meta-analysis synthesized the reported frequency of concurrent macular neovascularization (MNV) among selected eyes with author-defined shallow irregular retinal pigment epithelium (RPE) elevations in age-related macular degeneration (AMD) and chronic central serous chorioretinopathy (CSC). Nine databases were searched on 3 May 2026 for observational studies assessing contemporaneous MNV in phenotype-positive eyes. Studies were classified according to phenotype definition, disease context, unit of analysis and MNV ascertainment directness. Principal quantitative syntheses were restricted to clinically comparable Tier 1 eye-level cohorts, while Tier 2 evidence was examined in a restricted sensitivity analysis. Random-effects meta-analysis of logit-transformed proportions was performed separately by disease, with binomial-normal generalized linear mixed models (GLMM) used as sensitivity analyses. Certainty was assessed using a GRADE-style framework, and the review was registered in PROSPERO (CRD420261384416). Twenty-two reports were included, comprising five AMD and 17 CSC reports. Three selected fellow-eye AMD cohorts contributed 160 double-layer sign (DLS)-positive eyes to the principal AMD analysis; the pooled frequency of contemporaneous MNV was 52% (95% confidence interval [CI], 19%-84%; I[2] = 72.52%). Five selected chronic CSC cohorts contributed 232 flat irregular pigment epithelial detachment (FIPED)-positive eyes to the principal CSC analysis; the pooled frequency was 43% (95% CI, 25%-63%; I[2] = 61.32%). A restricted Tier 1 plus Tier 2 CSC sensitivity analysis yielded 39% (95% CI, 23%-57%; I[2] = 77.89%). GLMM sensitivity analyses produced similar point estimates, although confidence and prediction intervals remained wide. Certainty of evidence was very low. In selected phenotype-positive cohorts, contemporaneous MNV was identified in approximately one-half of DLS-positive AMD eyes and two-fifths of FIPED-positive chronic CSC eyes, but the estimates were imprecise. These findings should not be interpreted as diagnostic, prognostic, population-prevalence or treatment thresholds. Structural OCT phenotypes should prompt disease-contextualized multimodal characterization rather than stand-alone inference of MNV activity or treatment need.},
}

@article {pmid42636893,
year = {2026},
author = {Zhang, Y and Luan, F and Feng, J and Sun, W and Tao, Y},
title = {Dual-restricted AAV gene delivery via suprachoroidal administration mediates precision RPE SOCS3 restoration for dry age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115289},
doi = {10.1016/j.jconrel.2026.115289},
pmid = {42636893},
issn = {1873-4995},
abstract = {Dry age-related macular degeneration (dAMD) is a leading cause of irreversible vision loss, driven by chronic oxidative stress and inflammation in the retinal pigment epithelium (RPE). Disruption of key negative regulators of the JAK-STAT pathway, particularly SOCS3, contributes to this oxidative-inflammatory cascade. To address this, we developed a dual-restricted ocular gene delivery platform that combines suprachoroidal administration with an RPE-specific Best1 promoter, enabling localized, durable, and cell-restricted SOCS3 expression. Comparative analysis showed that intravitreal injection poorly transduced the RPE, whereas suprachoroidal delivery improved AAV access to the RPE/outer retinal region, and the Best1 promoter further restricted expression to RPE cells, reducing neural retinal off-target expression. In vitro, SOCS3 restoration suppressed STAT3 activation, inflammatory cytokine release, reactive oxygen species accumulation, mitochondrial disruption, and barrier impairment. In vivo, the dual-restricted system achieved long-term, ocular-localized expression for at least six months, reducing microglial/macrophage activation, inflammation, oxidative stress, and apoptosis, thereby preserving outer retinal architecture. Ocular and systemic safety assessments detected no overt toxicity under the tested conditions. Together, these findings support suprachoroidal AAV-Best1-SOCS3 delivery as a dual-restricted platform for localized modulation of oxidative-inflammatory retinal degeneration and warrant further preclinical evaluation.},
}

@article {pmid42637139,
year = {2026},
author = {Conforti, A and Cifuentes-González, C and Agrawal, KR and Agrawal, R},
title = {GLP-1 receptor agonists and ocular disease: Therapeutic promise, mechanistic insights and emerging safety signals.},
journal = {Drug discovery today},
volume = {},
number = {},
pages = {104786},
doi = {10.1016/j.drudis.2026.104786},
pmid = {42637139},
issn = {1878-5832},
abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes and obesity and are increasingly recognised for their pleiotropic effects beyond glycaemic control. Growing evidence suggests that these agents influence inflammatory, vascular and neuroprotective pathways relevant to ocular disease, creating opportunities for therapeutic repurposing while raising important questions regarding long-term ocular safety. This review crucially synthesises current mechanistic, preclinical and clinical evidence regarding the role of GLP-1 RAs across major ophthalmic conditions. Experimental studies consistently demonstrate anti-inflammatory, antioxidative and neurovascular-protective effects, particularly in diabetic retinopathy, whereas clinical studies suggest a potential benefit yet are limited by heterogeneous study designs and the absence of dedicated ophthalmic endpoints. We also examine emerging safety signals, including reported associations with nonarteritic anterior ischaemic optic neuropathy and neovascular age-related macular degeneration, highlighting the limitations of current observational evidence and the uncertainty surrounding causality. Finally, we discuss the translational potential of GLP-1 RAs in immune-mediated ocular diseases such as noninfectious uveitis and identify key priorities for future research. Because the clinical use of GLP-1 RAs continues to expand, carefully designed prospective studies integrating mechanistic insights with standardised ophthalmic outcomes will be essential to define both their therapeutic potential and long-term ocular safety.},
}

@article {pmid42637173,
year = {2026},
author = {Fritsch, S and Wall, K and Vaisband, M and Hasenauer, J and Schwenzer, N and Jauch, AS and Holz, FG and Curcio, CA and Ach, T},
title = {Fluorescence lifetime imaging microscopy of pigmented cells in age-related macular degeneration.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111216},
doi = {10.1016/j.exer.2026.111216},
pmid = {42637173},
issn = {1096-0007},
abstract = {This study characterized fibrosis-associated pigment changes in neovascular age-related macular degeneration (nAMD) using fluorescence lifetime imaging microscopy (FLIM). Retinal cross sections from human donor eyes with nAMD (n = 5; mean age 91.5 ± 2.1 years) and control eyes without maculopathy (n = 5; 82.5 ± 0.7 years) were analyzed at λexc 488 nm and λexc 780 nm. In total, 116 regions of interest (50 μm width each) were assessed across the fovea, parafovea, and areas of subretinal fibrosis in nAMD eyes and compared with corresponding locations in controls. Fluorescence lifetimes (FLTs) were evaluated using a linear mixed-effects model across pigment in unremarkable retinal pigment epithelium (RPE), pigment in RPE above fibrosis, pigment within fibrosis, and pigment in the choroid. At λexc 488 nm, FLTs were significantly prolonged in RPE above fibrosis (0.54 ± 0.04 ns) compared with unremarkable RPE (0.49 ± 0.04 ns, linear mixed-effect model: p = 0.04). Pigment within fibrosis (0.51 ± 0.03 ns) showed similar lifetimes to unremarkable RPE (p = 0.58), while choroidal pigment exhibited markedly shorter lifetimes (0.23 ± 0.04 ns; p < 0.001). At λexc 780 nm, pigment within fibrosis displayed shorter lifetimes (0.27 ± 0.03 ns) than unremarkable RPE (0.34 ± 0.04 ns, p = 0.04), and choroidal pigment again showed the shortest values (0.11 ± 0.01 ns; p < 0.001). Dual-wavelength FLIM reveals distinct lifetime patterns at fibrotic locations consistent with an RPE origin of fibrosis-associated pigment in nAMD.},
}