@article {pmid42926770,
year = {2026},
author = {Yang, J and Daniel, S and Hulleman, JD},
title = {An Inducible Model of RPE-Associated Hydroxyapatite Mineralization with Relevance to Drusen Formation in Age-Related Macular Degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.10.08.757467},
pmid = {42926770},
issn = {2692-8205},
abstract = {A cardinal feature of nonexudative age-related macular degeneration (AMD) is the accumulation of drusen between the retinal pigment epithelium (RPE) and Bruch's membrane, yet the mechanisms that initiate and promote drusen formation remain to be fully understood. Hydroxyapatite (HAP), a calcium-phosphate mineral identified within human drusen, has been proposed to contribute to drusen nucleation and is associated with increased likelihood of RPE atrophy. However, mechanistic studies providing insight into RPE-associated mineralization have been limited by a lack of easy-to-use and manipulatable culture models. Here, we established a rapid, inducible ARPE-19-based model of HAP mineralization. We found that ARPE-19 cells cultured in minimum essential media (MEM) supplemented with nicotinamide (NIC), sodium phosphate, and ascorbic acid (NaPAA) reproducibly formed HAP positive deposits, whereas mineralization was not observed while using standard DMEM/F12 medium, DMEM/F12 with NaPAA, MEM-NIC medium, or MEM-NIC medium with alternative osteogenic supplements (such as β-glycerophosphate, ascorbic acid, and dexamethasone). Scanning electron microscopy with energy dispersive X ray spectroscopy demonstrated that the formed deposits were enriched in calcium (Ca) and phosphorus (P) with Ca/P ratios comparable to drusen-associated HAP deposits from AMD donor tissue. ARPE-19-based HAP deposits were also closely associated with neutral lipid-rich material, staining positive for BODIPY around their core structure. Bulk RNA sequencing of mineralized ARPE-19 cells revealed extracellular matrix, angiogenic, inflammatory, and metabolic transcriptional changes in the absence of strong enrichment of canonical osteogenic pathways. Co-treatment of mineralizing cells with either pyrophosphate, EDTA, or sodium citrate significantly reduced mineral deposition, but these approaches were not able to reverse it. Together, these findings establish a tractable RPE mineralization model that recapitulates key features of AMD-associated HAP and provides a platform for investigating mechanisms of drusen-associated mineral formation.},
}

@article {pmid42927272,
year = {2026},
author = {Chakravarthy, H and Xi, J and Yoo, HS and Buss, A and Li, B and Bell, R and Haegert, A and Le Bihan, S and Granville, DJ and Matsubara, JA},
title = {Factor H polymorphism elevates granzyme B and impairs complement inhibition in human and mouse models.},
journal = {iScience},
volume = {29},
number = {11},
pages = {117957},
pmid = {42927272},
issn = {2589-0042},
abstract = {The complement factor H (CFH) Y402H polymorphism is a leading genetic risk factor for age-related macular degeneration (AMD). Here, we identify extracellular granzyme B (GzmB) as a crucial mediator connecting complement dysregulation to structural pathology. In non-AMD human donor eyes, the high-risk CFH genotype was associated with increased GzmB-positive choroidal mast cells, membrane attack complex deposition, and distinct vitronectin redistribution. Using in vitro human retinal pigment epithelium (RPE) cells, we demonstrate that complement fragment C5a triggers GzmB secretion and zonula occludens-1 disruption. RNA sequencing of GzmB-stimulated RPE cells confirmed transcriptomic signatures of barrier dysfunction and cellular stress. Furthermore, GzmB-deficient mice displayed preserved choroidal vitronectin compared with wild-type controls, supporting a role for GzmB in cleaving this terminal complement inhibitor. These findings delineate a pathogenic C5a-GzmB pathway compromising extracellular matrix integrity, implicating extracellular GzmB as a critical downstream mediator linking genetic risk to early AMD onset.},
}

@article {pmid42928338,
year = {2026},
author = {Wang, Y and Huang, Z and Tseng, Y and Ma, H and Chen, K and Pan, X and Ye, H and Cheng, T and Ge, J and Deng, J and Wang, X and Xia, J and Shen, J and Du, C and Lei, W and Mao, Z and Cui, H and Sheng, Y},
title = {The potential of ruxolitinib as a senomorphic therapy in alleviating neovascular age-related macular degeneration : Ruxolitinib inhibits CNV.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {42928338},
issn = {1479-5876},
support = {82401265//National Natural Science Foundation of China/ ; 82271619//National Natural Science Foundation of China/ ; SDCX-ZG-202503121//Postdoctoral Innovation Program of Shandong Province/ ; LZ24H120002//Natural Science Foundation of Zhejiang Province/ ; },
mesh = {Animals ; Pyrimidines ; Nitriles ; *Pyrazoles/therapeutic use/pharmacology ; *Choroidal Neovascularization/drug therapy/pathology/complications ; Humans ; *Macular Degeneration/drug therapy/pathology/complications ; *Cellular Senescence/drug effects ; Signal Transduction/drug effects ; Janus Kinase 2/metabolism ; Rats, Inbred BN ; Retinal Pigment Epithelium/pathology/drug effects ; STAT3 Transcription Factor/metabolism ; Janus Kinase 1/metabolism ; Rats ; Cell Line ; Janus Kinases/metabolism ; Male ; },
abstract = {BACKGROUND: Cellular senescence plays a key role in the pathogenesis of neovascular age-related macular degeneration (nAMD). Senomorphic therapy, which targets the senescence-associated secretory phenotype (SASP), holds promise for treating age-related diseases; however, effective senomorphic treatments for nAMD remain lacking.

METHODS: We screened a panel of senomorphic agents in bleomycin- and ionizing radiation (IR)-induced senescent ARPE-19 cells to identify a lead compound for nAMD. Bulk and single-cell RNA sequencing data were analyzed to explore JAK-STAT signaling activation. Ruxolitinib and siRNA were used to validate the role of the JAK1/2-STAT3 pathway in senescent retinal pigment epithelium (RPE). A laser-induced choroidal neovascularization (CNV) model was established in Brown-Norway rats for in vivo studies.

RESULTS: Ruxolitinib, a JAK1/2 inhibitor, most effectively suppressed SASP factors and complement C3 expression while restoring pigment epithelium-derived factor (PEDF) levels in senescent ARPE-19 cells. Knockdown of JAK1 or JAK2 significantly reversed the expression of vascular endothelial growth factor (VEGF), C3, and PEDF. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) revealed activation of the JAK-STAT pathway in nAMD patient samples, CNV models, and senescent RPE cells, which was corroborated in the CNV rat model. Inhibition of JAK1/2-STAT3 with ruxolitinib markedly reduced vascular leakage and CNV area, and accelerated recovery of retinal function. The combination of ruxolitinib with anti-VEGF therapy presented a better effect on inhibiting CNV area. Furthermore, intravitreal injection of ruxolitinib showed no significant structural or functional toxicity in normal rat retinas over one month.

CONCLUSIONS: Our study identifies the JAK1/2-STAT3 pathway as a key regulator of the SASP in senescent RPE and confirms its activation in nAMD and experimental CNV. Pharmacologic inhibition of this pathway with ruxolitinib effectively attenuates CNV progression with a favorable short-term safety profile, supporting its potential as a senomorphic therapy for nAMD.},
}

Animals
Pyrimidines
Nitriles
*Pyrazoles/therapeutic use/pharmacology
*Choroidal Neovascularization/drug therapy/pathology/complications
Humans
*Macular Degeneration/drug therapy/pathology/complications
*Cellular Senescence/drug effects
Signal Transduction/drug effects
Janus Kinase 2/metabolism
Rats, Inbred BN
Retinal Pigment Epithelium/pathology/drug effects
STAT3 Transcription Factor/metabolism
Janus Kinase 1/metabolism
Rats
Cell Line
Janus Kinases/metabolism
Male

@article {pmid42929416,
year = {2026},
author = {Babu, VS and Ghosh, S and Bammidi, S and Jiwon, R and Sharma, R and Meyer, D and Hose, S and Pattabiraman, PP and Sahel, JA and Kidley, NJ and Braz, NF and Slater, MJ and Lang, S and Ghosh, A and Handa, JT and Yi, J and Sripathi, S and Kannan, RM and Bharti, K and Sinha, D},
title = {AKT1-phosphorylated TERT assembles a FOXO3-MYC transcriptional complex that drives ERphagy and proteostasis in post-mitotic RPE.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-28},
doi = {10.1080/15548627.2026.2750048},
pmid = {42929416},
issn = {1554-8635},
abstract = {The retinal pigment epithelium (RPE) sustains lifelong proteostasis under chronic stress, yet how post-mitotic cells activate macroautophagy/autophagy when canonical kinase pathways suppress it remains unresolved. Here we demonstrate that AKT1 (protein kinase B alpha), drives autophagy through a non-canonical transcriptional mechanism triggered by isoform imbalance. In RPE and age-related macular degeneration (AMD) models, AKT2 (protein kinase B beta) hyperactivation destabilizes MTORC2 (mechanistic target of rapamycin complex 2) and engages RPS6KB/S6K (ribosomal protein S6 kinase beta) -mediated IRS-1 (insulin Receptor Substrate 1) inhibition, creating a feedforward autophagic arrest. Compensatory AKT1 activation via MTORC2 phosphorylates TERT (telomerase reverse transcriptase) at serine 824, driving nuclear translocation that is independent of telomere maintenance. In the nucleus, TERT assembles with FOXO3 (forkhead Box O3) and MYC (MYC proto-oncogene, bHLH transcription factor) into a tripartite transcriptional complex that occupies the EIF2AK3/PERK promoter (eukaryotic translation initiation factor 2-alpha kinase 3/ protein kinase R-like endoplasmic reticulum kinase), enabling EIF2AK3 transcriptional activation. This activity converts the unfolded protein response from pro-apoptotic to cytoprotective: EIF2AK3-ATF4 (activating transcription factor 4) signaling promotes core autophagy machinery biogenesis and selective ERphagy through the receptors TEX264 (testis expressed 264) and CCPG1(cell cycle progression 1), which prevents pathological EIF2AK3 clustering and preserves tubular ER architecture in diseased RPE. Using C. elegans phosphorylation-deficient mutants, mouse models and AMD patient iPSC-RPE, we establish that AKT1-mediated TERT phosphorylation is an evolutionarily conserved prerequisite for FOXO/DAF-16 nuclear function and lysosomal homeostasis in post-mitotic cells, offering therapeutic potential through targeted pharmacologic inhibition of AKT2.Abbreviations: ACTB: actin, beta; AKT1: AKT serine/threonine kinase 1; AKT2: AKT serine/threonine kinase 2; ALP: autophagy-lysosomal pathway; AMD: age-related macular degeneration, ATF4: activating transcription factor 4; ATG3: autophagy related 3; ATG4B: autophagy related 4B cysteine peptidase; ATG7: autophagy related 7; CCPG1: cell cycle progression 1; CFH: complement factor H; C57BL/6J: C57 black 6J; DMSO: dimethyl sulfoxide; MYC: MYC proto-oncogene, bHLH transcription factor; EIF2A/eIF2α: eukaryotic translation initiation factor 2A; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; ERN1/IRE-1α: endoplasmic reticulum to nucleus signaling 1; ERphagy: endoplasmic reticulum-selective autophagy; FOXO1: forkhead box O1; FOXO3: forkhead box O3; iPSC-RPE: induced pluripotent stem cell-derived retinal pigment epithelium; ITGB1/integrin β1: integrin subunit beta 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPKAP1/SIN1: MAPK associated protein 1; MTOR: mechanistic target of rapamycin kinase; MTORC1: MTOR complex 1; MTORC2: MTOR complex 2; PBS: phosphate-buffered saline; PI3K: phosphoinositide 3-kinase; RICTOR: RPTOR independent companion of MTOR complex 2; RPE: retinal pigment epithelium; RPTOR: regulatory associated protein of MTOR complex 1; SQSTM1/p62: sequestosome 1; TERT: telomerase reverse transcriptase; TEX264: testis expressed 264, ER-phagy receptor; UPR: unfolded protein response; VCL: vinculin; WT: wild type.},
}

@article {pmid42929689,
year = {2026},
author = {Nassisi, M and Eandi, CM and Donà, C and Pozzo Giuffrida, F and Cattaneo, J and Lavia, CA and Malerba, A and Galli, D and Mainetti, C and Gambaro, L and Faraldi, F and Dell'Arti, L and Mapelli, C and Casalino, G and Viola, F},
title = {AI-Based OCT Assessment of Anatomic Response During the Loading Phase of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {12},
pages = {62},
doi = {10.1167/iovs.67.12.62},
pmid = {42929689},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Intravitreal Injections ; Receptors, Vascular Endothelial Growth Factor/administration & dosage/therapeutic use ; Recombinant Fusion Proteins/administration & dosage/therapeutic use ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Bevacizumab/administration & dosage/therapeutic use ; Female ; Visual Acuity ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Aged ; Aged, 80 and over ; Treatment Outcome ; },
abstract = {PURPOSE: To compare functional and anatomic outcomes after the loading phase of intravitreal bevacizumab, aflibercept 2 mg, or faricimab in treatment-naive neovascular age-related macular degeneration (nAMD), using artificial intelligence (AI)-based optical coherence tomography (OCT) analysis.

METHODS: This multicenter retrospective cohort study included 224 eyes. Patients received three monthly injections of bevacizumab (n = 80), aflibercept 2 mg (n = 78), or faricimab (n = 66). Best-corrected visual acuity (BCVA) and spectral-domain OCT were assessed at baseline and week 12. AI-based segmentation quantified volumetric measurements of intraretinal fluid (IRFv), subretinal fluid (SRFv), and pigment epithelial detachment. The primary outcome was qualitative dry macula (absence of intraretinal fluid and subretinal fluid). An exploratory composite OCT biomarker (ΔCOMBO), defined as the lesser percentage reduction between IRFv and SRFv, was evaluated as a hypothesis-generating metric using receiver operating characteristic analysis. Baseline-adjusted analyses and multivariable logistic regression were performed.

RESULTS: Descriptive within-group analyses showed improvement in BCVA and reduction in OCT parameters at week 12 in treatment groups. BCVA improvement was statistically significant in the bevacizumab and faricimab groups. In baseline-adjusted analyses, between-group differences emerged for OCT outcomes, whereas no significant between-group differences were observed for BCVA. Higher rates of dry macula were observed with faricimab (80.3%) and aflibercept 2 mg (67.9%) compared with bevacizumab (41.3%) (P < 0.001). The exploratory composite metric ΔCOMBO showed high discriminative performance (area under the curve = 0.959; 95% confidence interval, 0.907-0.999).

CONCLUSIONS: All agents improved functional and anatomic outcomes after the loading phase in treatment-naive nAMD. Baseline-adjusted analyses showed differences in anatomic response patterns across treatments. Exploratory AI-based OCT biomarkers may help characterize short-term anatomic response; however, these findings require external validation.},
}

Humans
*Tomography, Optical Coherence/methods
Retrospective Studies
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
Intravitreal Injections
Receptors, Vascular Endothelial Growth Factor/administration & dosage/therapeutic use
Recombinant Fusion Proteins/administration & dosage/therapeutic use
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Bevacizumab/administration & dosage/therapeutic use
Female
Visual Acuity
Male
*Wet Macular Degeneration/drug therapy/diagnosis/physiopathology
Aged
Aged, 80 and over
Treatment Outcome

@article {pmid42929859,
year = {2026},
author = {Srivastava, GK and Shukla, P and Millas, SC and Lokanathan, Y},
title = {Artificial Intelligence as a Catalyst for Cell-Based Therapies in Retinal Disease.},
journal = {Cells},
volume = {15},
number = {20},
pages = {},
pmid = {42929859},
issn = {2073-4409},
mesh = {Humans ; *Artificial Intelligence ; *Cell- and Tissue-Based Therapy/methods ; *Retinal Diseases/therapy ; Animals ; },
abstract = {Retinal degenerative diseases, including age-related macular degeneration (AMD), retinitis pigmentosa (RP), and Stargardt disease, represent leading causes of irreversible vision loss worldwide, collectively affecting hundreds of millions of people. Cell-based therapies, particularly those leveraging induced pluripotent stem cells (iPSCs), retinal pigment epithelium (RPE) transplantation, and CRISPR-Cas9 gene editing, have emerged as promising treatment modalities that may preserve, replace, or partially restore retinal function. However, these approaches face significant challenges in patient stratification, manufacturing consistency, surgical precision, and long-term outcome monitoring. Artificial intelligence (AI), encompassing machine learning (ML), deep learning (DL), and computer vision, is increasingly being integrated across the cell therapy pipeline to address these limitations. This review comprehensively explores the role of AI in enhancing cell-based retinal therapies, spanning disease diagnosis and patient selection, stem cell quality control and differentiation optimization, CRISPR off-target detection, retinal organoid characterization, scalable manufacturing, and post-transplantation monitoring through multimodal retinal imaging. Throughout, we distinguish direct retinal cell-therapy evidence from retinal-adjacent, cross-domain, and conceptual evidence. We also propose an AI-powered end-to-end pipeline that connects patient profiling through gene editing, cell production, and transplantation to longitudinal outcomes tracking (a forward-looking framework that needs to be clinically validated in future). While AI offers powerful tools to enhance efficacy, reproducibility, and personalization, it does not replace the clinical and biological foundations of cell therapy. Critical challenges remain, including data scarcity, algorithmic interpretability, regulatory compliance, and clinical validation. This review concludes that the strategic integration of AI has plausible potential to become supportive infrastructure for scalable and reproducible cell-based treatments for retinal diseases, although its necessity has not been demonstrated and prospective clinical validation is still required, and biological insight and rigorous empirical verification remain fundamental.},
}

Humans
*Artificial Intelligence
*Cell- and Tissue-Based Therapy/methods
*Retinal Diseases/therapy
Animals

@article {pmid42930766,
year = {2026},
author = {Cusumano, A and Sebastiani, J and D'Ambrosio, M and Regine, B and Cascella, R and Giardina, E and Falsini, B},
title = {Retinal Function, Risk Genotypes and Response to Nanosecond Laser Therapy in Intermediate AMD: A Pilot Study.},
journal = {Journal of personalized medicine},
volume = {16},
number = {10},
pages = {},
pmid = {42930766},
issn = {2075-4426},
abstract = {Purpose: To investigate whether the major age-related macular degeneration (AMD) risk variants, Complement Factor H (CFH rs1061170, T/C) and Age-Related Maculopathy Susceptibility 2 (ARMS2 rs10490924, G/T), are associated with differences in full-field electroretinographic (ERG) function among patients with intermediate AMD (iAMD), and to evaluate whether retinal functional responses to subthreshold nanosecond laser (2RT[®]) therapy are influenced by these genetic variants. Methods: This retrospective observational study included 23 iAMD patients who underwent genotyping for rs1061170 and rs10490924 and subthreshold nanosecond laser treatment (2RT[®]). For each genetic variant, patients were stratified into those with the risk allele and those with the corresponding wild-type genotype. Full-field ERG measurements were obtained at baseline and at 1 and 3 months after 2RT[®] treatment. Twenty-six age-matched healthy subjects served as controls for the electrophysiological comparisons. Results: Patients with the CFH risk allele showed lower photopic b-wave amplitudes than CFH WT/negative patients overall (group effect: p = 0.0431, partial η[2] = 0.1809), whereas no corresponding group effect was observed for ARMS2 genotypes (p = 0.6805). Following 2RT treatment, mixed rod-cone amplitude showed a significant effect of time (Greenhouse-Geisser-corrected p = 0.0355), with mean amplitudes increasing at 1 month and remaining above baseline at 3 months. Photopic b-wave amplitude also changed significantly over time in both the CFH (p = 0.0370) and ARMS2 (p = 0.0342) stratifications. No significant genotype-by-time interactions were found, indicating that no genotype-dependent difference was detected in the functional response to 2RT according to CFH or ARMS2 genotype. PhNR amplitude and peak time showed no significant group or time effects. Conclusions: The CFH risk allele was associated with lower photopic b-wave amplitudes, whereas no corresponding difference was observed for ARMS2 genotypes. Following 2RT treatment, mixed rod-cone and photopic b-wave amplitudes showed significant changes over the 3-month follow-up, with no significant genotype-by-time interactions. These preliminary findings provide no evidence that the functional response to 2RT differs according to CFH or ARMS2 genotypes and require confirmation in larger controlled studies.},
}

@article {pmid42930807,
year = {2026},
author = {Gandhi, S and Balas, M and Wang, P and Arjmand, P},
title = {Temporal, Phenotypic, and Treatment-Context Heterogeneity in Retinal Vasculitis Reporting with Pegcetacoplan: A United States Pharmacovigilance Study.},
journal = {Journal of personalized medicine},
volume = {16},
number = {10},
pages = {},
pmid = {42930807},
issn = {2075-4426},
abstract = {Background/Objectives: Pegcetacoplan slows geographic atrophy (GA) progression, but postmarketing retinal vasculitis remains an important safety concern. We evaluated whether retinal vasculitis reporting changed over time, whether the reported phenotype changed with respect to occlusive coding, and whether vasculitis was associated with identifiable treatment contexts. Methods: We analyzed the United States (US) Food and Drug Administration Adverse Event Reporting System (FAERS) data from 17 February 2023 through 31 December 2025. Strict retinal vasculitis reports required pegcetacoplan to be coded as the primary-suspect drug. Faricimab was used as a descriptive contemporaneous intravitreal comparator because US exposure estimates could be constructed over the same period; it was not treated as a safety-neutral control. Separately, within all US primary-suspect Syfovre reports, we examined whether another anti-vascular endothelial growth factor (anti-VEGF) agent was co-reported. These anti-VEGF agents were evaluated as treatment-context variables rather than as temporal comparators. Results: We identified 79 US primary-suspect Syfovre retinal vasculitis reports, of which 58 had quarter-assignable clinical event dates. Overall, 42/79 (53.2%) contained an occlusive-specific vasculitis preferred term and 37/79 (46.8%) did not. Pegcetacoplan reporting declined from 4.09 to 0.38 reports per 10,000 estimated vials between the pre-change and post-change periods (reporting-rate ratio 0.09, 95% confidence interval [CI] 0.05-0.16; p < 0.001). Faricimab reporting also declined; the ratio of reporting-rate ratios was 0.79 (95% CI 0.22-2.78; p = 0.711), with wide uncertainty. Among temporally assignable pegcetacoplan reports, occlusive-specific coding decreased from 16/21 (76.2%) before the change to 8/30 (26.7%) afterward (p < 0.001). Another anti-VEGF agent was listed in 19/79 vasculitis reports versus 50/571 nonvasculitis reports (reporting odds ratio 3.30, 95% CI 1.83-5.96; p < 0.001); however, adjustment for medication count and report completeness attenuated the estimate to 1.89 (95% CI 0.99-3.61; p = 0.052). Conclusions: Pegcetacoplan retinal vasculitis reporting declined over time, but the descriptive faricimab comparison was too imprecise to determine whether the proportional temporal change differed between products. The reported phenotype shifted away from occlusive-specific coding, while the anti-VEGF co-reporting association was sensitive to adjustment for documentation intensity. These findings characterize heterogeneity in spontaneous safety reporting and do not establish patient-level risk, changes in clinical event severity, or causal treatment effects.},
}

@article {pmid42931620,
year = {2026},
author = {Suleimenov, M and Kadyrgaliyev, B and Kanafyanova, E and Meyermanova, Z and Abdullina, V and Zhankalova, Z and Yeshmanova, A and Abdykulova, A and Almukhambetova, S and Kulmaganbetov, M},
title = {Outcomes of Intravitreal Anti-VEGF Therapy for Neovascular Age-Related Macular Degeneration in Kazakhstan.},
journal = {Vision (Basel, Switzerland)},
volume = {10},
number = {4},
pages = {},
pmid = {42931620},
issn = {2411-5150},
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss among older adults. Although randomised controlled trials have demonstrated the robust efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy, real-world outcomes often differ markedly from trial findings. This study aimed to evaluate the anatomical and functional outcomes of anti-VEGF therapy in a clinical cohort of nAMD patients, including a subgroup that received adjunctive rescue photodynamic therapy (PDT) with verteporfin.

METHODS: This single-centre, retrospective observational cohort study included 568 patients (634 eyes) with nAMD treated with intravitreal anti-VEGF injections. Bevacizumab was used in 49% of eyes, ranibizumab in 44%, and aflibercept in 7%. Best recorded visual acuity (BRVA) and central retinal thickness (CRT) measured by optical coherence tomography (OCT) were recorded at baseline and at the final documented follow-up. Eyes with eccentric fixation were excluded from BRVA analysis but were retained for CRT analysis.

RESULTS: Mean patient age was 71.7 ± 8.8 years, and 67.6% of eyes were from female patients. The mean number of anti-VEGF injections was 5 ± 5.3 per eye; the mean follow-up duration was 11.5 months. Mean CRT decreased significantly from 347.3 ± 27.5 μm at baseline to 324.9 ± 28.8 μm at final follow-up (p < 0.001). Mean BRVA (logMAR) improved modestly from 0.98 ± 0.55 (Snellen ~20/190; ~35 ETDRS letters) to 0.93 ± 0.56 (Snellen ~20/175; ~37.5 ETDRS letters) (p < 0.001), with 67.9% of eyes demonstrating BRVA stability (change < 0.1 logMAR). Rescue PDT was administered in 10.3% of eyes.

CONCLUSIONS: In this real-world cohort, anti-VEGF therapy was associated with significant anatomical improvement, as measured by CRT reduction, while functional outcomes were characterised by visual stabilisation rather than substantial gains.},
}

@article {pmid42932769,
year = {2024},
author = {Qiu, J and Wu, J and Wei, H and Shi, P and Zhang, M and Sun, Y and Li, L and Liu, H and Liu, H and Hou, S and Zhao, Y and Shi, X and Xian, J and Qu, X and Zhu, S and Pan, L and Chen, X and Zhang, X and Jiang, S and Wang, K and Yang, C and Chen, M and Fan, S and Hu, J and Lv, A and Miao, H and Guo, L and Zhang, S and Pei, C and Fan, X and Lei, J and Wei, T and Duan, J and Liu, C and Xia, X and Xiong, S and Li, J and Lam, K and Lo, B and Tham, YC and Wong, TY and Wang, N and Yuan, W},
title = {Development and Validation of a Multimodal Multitask Vision Foundation Model for Generalist Ophthalmic Artificial Intelligence.},
journal = {NEJM AI},
volume = {1},
number = {12},
pages = {AIoa2300221},
doi = {10.1056/AIoa2300221},
pmid = {42932769},
issn = {2836-9386},
abstract = {BACKGROUND: Specialized single-use, single-modality models often have limited or no generalization to new diseases, modalities, and clinical tasks. Foundation models are built for multipurpose use, enabling them to perform tasks even when not specifically pretrained for them, and to adapt to different clinical applications.

METHODS: We present VisionFM, an artificial intelligence foundation model for ophthalmology pretrained on 3.4 million images from over 500,000 individuals, covering diverse ophthalmic diseases, imaging modalities and devices, and clinical scenarios. Pretrained based on eight modalities, VisionFM was tested for multiple applications, including disease screening and detection, prognosis and prediction, and segmentation of lesions and anatomical structures, on an ophthalmic database comprising 53 public and 12 private datasets. We compared the model against ophthalmologists with varying experience in ophthalmic and systemic disease diagnoses.

RESULTS: VisionFM outperformed baseline deep learning approaches in diagnosing ocular diseases, achieving an average area under the receiver operating characteristic curve (AUROC) of 0.950 (95% confidence interval [CI], 0.941 to 0.959) across eight disease categories and five imaging modalities in internal validation. In external validation, VisionFM achieved an AUROC of 0.945 (95% CI, 0.934 to 0.956) in fundus-based diabetic retinopathy recognition, and an AUROC of 0.974 (95% CI, 0.966 to 0.983) in optical coherence tomography-based age-related macular degeneration recognition. In a comparative study of diagnostic accuracy of 12 ocular diseases from fundus photographs, VisionFM shows diagnostic accuracy close to that of intermediate-level ophthalmologists. Its generalizability extends to new imaging modalities and devices, effectively handling dataset shifts. For example, VisionFM accurately graded diabetic retinopathy with an AUROC of 0.935 (95% CI, 0.902 to 0.964) using an imaging modality it was never exposed to during pretraining. Furthermore, VisionFM is able to predict both glaucoma progression and the presence of intracranial tumors directly from fundus photographs.

CONCLUSIONS: VisionFM provides an efficient platform for diagnosis or prediction of multiple diseases using multiple imaging modalities and is scalable to incorporate additional data, modalities, and applications via its open-sourced model weights and codebase. (Funded by the Research Grants Council (RGC) of Hong Kong SAR and others.).},
}

@article {pmid42932916,
year = {2026},
author = {Ajisegiri, SB and Alexandre, FJ and Brokemond, AJ and Gonzalez, SB and Amamoo, R and Shivam, P and Lindsey, ML and Martin, PM and Thounaojam, MC and Jadeja, RN and Nde, PN},
title = {The Emerging Functional Landscape of piRNAs in Ocular Health and Disease.},
journal = {Function (Oxford, England)},
volume = {},
number = {},
pages = {e900302026R1},
doi = {10.1152/function.90030.2026},
pmid = {42932916},
issn = {2633-8823},
abstract = {P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a distinct class of small non-coding RNAs increasingly recognized as regulators of gene expression beyond their canonical function in PIWI-dependent transposon silencing. First characterized in the germline, recent evidence demonstrates that PIWI-piRNA pathways are active in somatic tissues and contribute to cellular homeostasis and adaptive stress responses through epigenetic, transcriptional, post-transcriptional, and translational mechanisms. Although piRNAs regulate several diseases, their roles in ocular physiology and pathology remain poorly understood. In the eye, piRNA pathways may govern retinal homeostasis and responses to oxidative stress, inflammation, angiogenesis, and fibrosis. This review synthesizes current knowledge on piRNA biogenesis, molecular mechanisms, and emerging functions in ocular tissues and examines evidence linking PIWI-piRNA dysregulation to major ocular diseases, including age-related macular degeneration, diabetic retinopathy, retinopathy of prematurity, and subretinal fibrosis. We evaluate the current evidence and highlight that, although disease-associated piRNA signatures and emerging mechanistic links to angiogenesis, oxidative stress, fibrosis, and cellular stress responses have been reported, most findings remain correlative and lack physiological validation. We discuss key challenges, including incomplete piRNA annotation, cell-type-specific activity, and variability in PIWI-piRNA regulatory mechanisms. We also outline future perspectives for defining the roles of PIWI-piRNA networks in ocular physiology and evaluating their potential as biomarkers and therapeutic targets for vision-threatening diseases.},
}

@article {pmid42934560,
year = {2026},
author = {Kamao, H and Hiraki, R and Yuto, D and Miki, A and Kimura, S},
title = {Noninfectious intraocular inflammation with hypopyon after intravitreal aflibercept 8 mg injection for neovascular age-related macular degeneration: a case report.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42934560},
issn = {1471-2415},
mesh = {Humans ; Male ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage/antagonists & inhibitors ; *Recombinant Fusion Proteins/adverse effects/administration & dosage ; Aged, 80 and over ; Intravitreal Injections ; *Angiogenesis Inhibitors/adverse effects/administration & dosage ; *Wet Macular Degeneration/drug therapy ; Visual Acuity ; Aqueous Humor ; },
abstract = {BACKGROUND: Herein, we report a case of noninfectious intraocular inflammation (IOI) with hypopyon after an intravitreal aflibercept 8 mg injection for neovascular age-related macular degeneration.

CASE PRESENTATION: An 87-year-old Japanese man with neovascular age-related macular degeneration in the right eye was switched from intravitreal aflibercept 2 mg to aflibercept 8 mg to extend the treatment interval. Three days after the third aflibercept 8 mg injection, the patient presented with decreased vision without ocular pain. Slit-lamp examination revealed mild conjunctival injection and anterior chamber cells. Despite treatment with topical corticosteroids, the inflammation worsened the following day, with increased anterior chamber cells accompanied by a highly mobile hypopyon that shifted with head position. Smear microscopy of the aqueous humor showed neutrophils without detectable bacteria; the bacterial and fungal cultures were negative. Given the mild conjunctival injection, absence of ocular pain, and negative microbiological findings, noninfectious IOI was considered. The hypopyon rapidly resolved after a subconjunctival betamethasone injection on day 5. On day 8, vitritis and vitreous haze were observed and sub-Tenon triamcinolone acetonide was administered. By day 44, the best-corrected visual acuity had recovered to 20/20 and all inflammatory findings had completely resolved.

CONCLUSIONS: Noninfectious IOI with hypopyon may occur after an intravitreal aflibercept 8 mg injection. Even when hypopyon is present after an anti-vascular endothelial growth factor injection, noninfectious IOI should be included as a differential diagnosis in addition to infectious IOI.},
}

Humans
Male
*Receptors, Vascular Endothelial Growth Factor/administration & dosage/antagonists & inhibitors
*Recombinant Fusion Proteins/adverse effects/administration & dosage
Aged, 80 and over
Intravitreal Injections
*Angiogenesis Inhibitors/adverse effects/administration & dosage
*Wet Macular Degeneration/drug therapy
Visual Acuity
Aqueous Humor

@article {pmid42935864,
year = {2026},
author = {Zhou, Z and Hunt, D and Harris, JM and Fliotsos, MJ and Sudhakar, V and Pajic, M and Hadziahmetovic, M},
title = {Comparative Large Language Models Evaluation for Age-Related Macular Degeneration Diagnosis on OCT and Rubric-Based Diagnostic Quality Assessment.},
journal = {Ophthalmology science},
volume = {6},
number = {11},
pages = {101372},
pmid = {42935864},
issn = {2666-9145},
abstract = {PURPOSE: To develop and validate a rubric-based large language model (LLM) evaluator for assessing the diagnostic quality of LLM-generated age-related macular degeneration (AMD) diagnoses from OCT scans, benchmarked against human evaluators, and, as a secondary aim, to characterize the diagnostic capability of the underlying LLMs.

DESIGN: Retrospective study primarily developing and validating a rubric-based LLM evaluator for assessing the diagnostic quality of LLM-generated diagnoses on retinal OCT, with the diagnostic performance of the LLMs assessed as a secondary analysis.

PARTICIPANTS: A total of 140 OCT scans (70 of choroidal neovascular membrane, 70 of drusen), 6 diagnoser models (GPT-4.1, GPT-4o, o4-mini, Gemini-2.5-Flash, GPT-5-mini, and GPT-5.5), and 4 evaluator models (GPT-4.1, GPT-5-mini, o4-mini, and Gemini-2.5-Flash) were included in this study.

METHODS: We developed a 2-stage workflow to automate OCT diagnosis associated with AMD. First, LLM "diagnosers" are prompted to provide a diagnosis in natural language from OCT scans. Second, LLM "evaluators" grade the diagnosis against a predetermined rubric for accuracy, imaging features, differential diagnosis, and clarity. A pilot experiment on 20 OCT scans benchmarked four LLM evaluators against a human evaluator using the identical rubric. Interrater reliability between the selected LLM evaluator and 2 retinal specialists was further assessed across 560 image-diagnosis pairs using intraclass correlation coefficients (ICCs) and two-1-sided test equivalence analysis. The best-performing LLM evaluator was then deployed in a full-scale analysis on 140 OCT scans to grade all 6 diagnoser models.

MAIN OUTCOME MEASURES: Average gradings, standard deviation, P value, correlation coefficient, ICC values, paired t-test P values, and two-1-sided test equivalence bounds between human and LLM evaluators.

RESULTS: In the pilot analysis, Gemini-2.5-Flash demonstrated the strongest alignment with the human evaluator. In the expanded experiment across 560 image-diagnosis pairs, ICC analysis confirmed that Gemini-2.5-Flash's agreement with human specialists (ICC = 0.897) was comparable to interspecialist agreement (ICC = 0.806), and two-1-sided test analysis supported statistical equivalence with human scoring, with a mean difference of 0.123 points. In the large-scale evaluation, GPT-5.5 achieved the highest average diagnoser score (6.3/8), followed by GPT-5-mini (5.0) and Gemini-2.5-Flash (4.9).

CONCLUSIONS: Large language model evaluators demonstrate a high level of agreement with human evaluator in supervising the quality of AMD diagnoses on OCT scans generated by LLM diagnosers. This workflow demonstrates the potential of LLM-powered automation for diagnostic quality evaluation in ophthalmology clinical practice.

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

@article {pmid42935887,
year = {2026},
author = {Camacho, P and Ribeiro, E and Pereira, B and Nascimento, J and Rosa, PC and Henriques, J and Barrão, S and Afonso, J and Delgadinho, M and Ginete, C and Brito, M and Cabral, D},
title = {Changes in expression of DNA-methyltransferase in neovascular age-related macular degeneration: Anti-VEGF response or disease severity?.},
journal = {American journal of ophthalmology case reports},
volume = {44},
number = {},
pages = {102681},
pmid = {42935887},
issn = {2451-9936},
abstract = {PURPOSE: Recent studies suggest distinct patterns of DNA methyltransferase (DNMT) expression across different stages of age-related macular degeneration (AMD). However, whether these variations can be modulated by conventional therapeutic approaches remains unexplored. This study investigates DNMT expression dynamics in two patients with exudative neovascular AMD (nAMD) during the initial months of anti-VEGF treatment.

OBSERVATIONS: Case 1, a female in her 90s was seen for sudden loss of vision secondary to macular hemorrhage. During type 1 macular neovascularization (t1MNV) anti-VEGF treatment, DNMT analysis revealed sustained upregulation of DNMT1 (+116%) and DNMT3b (+179%) while exudative MNV remained presisted.Case 2, a female in her 70s and asymptomatic subretinal fluid secondary to t1MNV showed a distinct DNMT expression pattern, with a more modest increase in DNMT1 (+28.9%) and DNMT3b (+17.6%) when exudation was resolved.

CONCLUSIONS: We hereby report varying DNMTs expression in nAMD patients with different disease manifestations giving new insights into the dynamic nature of epigenetic modifications in response to anti-VEGF treatment.},
}

@article {pmid42936036,
year = {2026},
author = {Rezaee, K and Farsi, S and Zadeh, HG},
title = {Deep Learning for Multi-Disease OCT Classification in Clinical Retina Practice Using Attention Mechanisms and Contrastive Learning.},
journal = {Healthcare technology letters},
volume = {13},
number = {1},
pages = {e70106},
pmid = {42936036},
issn = {2053-3713},
abstract = {Artificial intelligence (AI) is increasingly used in ophthalmic imaging to support early detection of vision-threatening retinal diseases such as age-related macular degeneration, diabetic retinopathy (DR) and choroidal neovascularisation (CNV). However, optical coherence tomography (OCT)-based deep learning models may remain sensitive to image degradation, struggle to resolve subtle inter-class morphological differences and show reduced reliability beyond controlled benchmark settings. We propose AESNet-SEC, a lightweight attention-enhanced SqueezeNet framework integrating multi-scale dilated convolutions, spatial attention, squeeze-and-excitation recalibration and contrastive representation learning. The framework was evaluated on the Retinal OCT-C8 dataset (24,000 images; eight classes) and a prospectively collected clinical dataset from Zeyaei Hospital, Iran (9732 OCT B-scans; four classes). AESNet-SEC achieved 98.56% accuracy on OCT-C8 and 96.33%-96.98% across four repeated clinical evaluations. Ablation and ROC analyses showed the strongest overall discrimination for the complete configuration, while controlled Gaussian-noise testing revealed greater degradation for DR and drusen. Grad-CAM visualisations highlighted anatomically plausible retinal regions, with independent retinal-specialist review providing qualitative support for the observed activation patterns. Overall, AESNet-SEC combines strong multi-class discrimination, computational efficiency, controlled robustness and visual interpretability, while broader patient-disjoint, multi-centre validation remains necessary.},
}

@article {pmid42936152,
year = {2026},
author = {Moshtaghion, SM and Shayan, M and Ramakrishnan, S and Ham, A and Gharehkoshan, AS and Morley, MG and Zebardast, N and Díaz-Corrales, FJ and Rodríguez de la Rúa, E and Husain, D and Sobrin, L and Elze, T and Friedman, DS and Eslami, M},
title = {Retinal neurodegeneration as accelerated ocular aging: a review of nutritional and metabolic supplements.},
journal = {Frontiers in aging},
volume = {7},
number = {},
pages = {1912337},
pmid = {42936152},
issn = {2673-6217},
abstract = {Retinal neurodegeneration is a major cause of irreversible vision loss and a shared feature of age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma (GL). Increasing evidence suggests that these conditions share important pathways with retinal aging, including mitochondrial dysfunction, metabolic insufficiency, redox imbalance, chronic low-grade inflammation, and progressive neuronal vulnerability. While antioxidant and micronutrient supplementation, most notably the Age-Related Eye Disease Study (AREDS) formulations, has demonstrated benefit in selected AMD populations, emerging metabolic and nutraceutical strategies targeting aging-related pathways are of unproven benefit. In this review, following a brief overview of the current landscape of investigated supplements, we synthesize preclinical and clinical evidence for a group of metabolic supplements, including nicotinamide adenine dinucleotide (NAD[+]) boosters, citicoline, pyruvate, and omega-3 fatty acids, that directly modulate mitochondrial bioenergetics, cellular redox state, membrane integrity, and neuroinflammatory signaling-pathways that are recognized hallmarks of biological aging and are particularly relevant to aging-related processes implicated in retinal neurodegeneration. Using a structured literature and clinical trial search, we summarize mechanistic insights and translational findings across AMD, DR, and glaucoma, emphasizing convergence on core pathways linking retinal neurodegeneration and ocular aging. Overall, current evidence supports biological plausibility and early functional or biomarker signals for these agents, particularly in glaucoma and diabetic retinal disease, although long-term efficacy remains unproven. Framing retinal disease at the intersection of neurodegeneration and aging biology, this review highlights metabolic supplementation as a promising but evolving strategy for preserving retinal function.},
}

@article {pmid42936242,
year = {2026},
author = {Yousuf, SJ},
title = {Associations Between Electronic Cigarettes, Smokeless Tobacco, and Age-Related Macular Degeneration in the 2017 United States National Health Interview Survey - Reply.},
journal = {Journal of vitreoretinal diseases},
volume = {10},
number = {1},
pages = {182},
pmid = {42936242},
issn = {2474-1272},
}

@article {pmid42936559,
year = {2026},
author = {Cai, L and Hou, K and Mo, Z and Ding, S},
title = {A multi-class fundus disease classification framework based on self-supervised contrastive learning and dual-branch network.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1932626},
pmid = {42936559},
issn = {2296-858X},
abstract = {INTRODUCTION: Fundus diseases including diabetic retinopathy, glaucoma, and age-related macular degeneration are primary causes of blindness worldwide. Manual interpretation of retinal images is time-consuming and heavily reliant on clinical expertise. Although deep learning has shown promise in automated fundus image analysis, its performance remains highly data-dependent, requiring large amounts of expert annotations. Moreover, single-architecture models may have limited capacity to capture the diverse pathological features present in fundus images.

METHODS: This study proposes a unified framework integrating self-supervised contrastive pre-training with a hybrid dual-branch architecture. Pre-training on unlabeled fundus images enables the model to learn generalizable representations, thereby reducing reliance on manual annotations. The dual-branch design combines EfficientNet-B4 for fine-grained detail extraction and MambaOut for large receptive field modeling. Their outputs are adaptively fused via a learnable cross-fusion module. A dendritic classifier is adopted to further improve classification performance. Comprehensive evaluations were conducted on two public datasets, OIHC and FIVES.

RESULTS: On the OIHC dataset, the proposed model achieved an F1-score of 96.32 ± 0.38% and a Kappa coefficient of 95.89 ± 0.43%. On the FIVES dataset, it attained 95.10 ± 0.54% and 93.49 ± 0.71%. The macro-average AUC exceeded 98% on both datasets. Ablation studies demonstrated the contribution of each component to the overall performance.

CONCLUSION: This study indicates that combining self-supervised pre-training with a hybrid dual-branch architecture is a feasible approach for multi-class fundus disease classification. Interpretability analyses suggest that the model's attention regions partially overlap with clinically relevant pathological features. The framework achieved competitive performance on both datasets, showing its potential utility in scenarios with limited annotated data. Future work will focus on multi-center validation and model compression for lightweight architecture design.},
}

@article {pmid42938335,
year = {2026},
author = {Lampsas, S and Agapitou, C and Chardalia, GM and Soulimiotis, D and Papastamopoulos, K and Theodossiadis, P and Chatziralli, I},
title = {Epigenetic Regulation and Gut Microbiota Dysbiosis in Age-Related Macular Degeneration.},
journal = {Genes},
volume = {17},
number = {10},
pages = {},
pmid = {42938335},
issn = {2073-4425},
mesh = {Humans ; *Macular Degeneration/genetics/microbiology/pathology ; *Epigenesis, Genetic ; *Gastrointestinal Microbiome/genetics ; *Dysbiosis/genetics/microbiology ; DNA Methylation/genetics ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment. Beyond the classical pathogenetic pathways, increasing evidence suggests that epigenetic regulation and the gut-retina axis may substantially contribute to AMD development and progression. This review synthesizes current evidence on two increasingly recognized and interconnected domains of AMD pathogenesis: epigenetic regulation and gut microbiota dysbiosis. Epigenetic processes, such as DNA methylation, histone modifications, and non-coding RNAs, can influence gene function involved in oxidative stress responses, complement regulation, angiogenesis, and inflammation, while several related markers have emerged as potential diagnostic and prognostic biomarkers. Moreover, growing evidence suggests a functional gut-retina axis, in which alterations in the gut microbiota impair intestinal barrier function and facilitate the systemic passage of bacteria and microbial metabolites, potentially affecting retinal inflammation and immune responses. Furthermore, several microbial metabolites, including short-chain fatty acids, lipopolysaccharide, bile acids, tryptophan derivatives, and trimethylamine-N-oxide, may have either protective or harmful effects on retinal and choroidal homeostasis, with altered circulating and fecal concentrations reported in patients with AMD compared with controls. These findings support AMD as a systemically and molecularly interconnected disorder, while further longitudinal, mechanistic, and multi-omics studies are required to establish causality, define interactions between epigenetic and microbiome-related pathways, and clarify their potential utility as biomarkers and therapeutic targets.},
}

Humans
*Macular Degeneration/genetics/microbiology/pathology
*Epigenesis, Genetic
*Gastrointestinal Microbiome/genetics
*Dysbiosis/genetics/microbiology
DNA Methylation/genetics
Animals

@article {pmid42923632,
year = {2026},
author = {Chen, H and Chen, W},
title = {From bench to bedside: translational advances, therapeutic targets, and delivery strategies in diabetic retinopathy.},
journal = {American journal of translational research},
volume = {18},
number = {9},
pages = {8254-8278},
pmid = {42923632},
issn = {1943-8141},
abstract = {Diabetic retinopathy (DR) is a leading cause of preventable blindness in adults of working age. Anti-vascular endothelial growth factor (anti-VEGF) therapy is the reference standard for diabetic macular edema (DME), yet in randomized cohorts, approximately 30-40% of DME eyes still show central macular thickening after six months of continuous treatment. In proliferative DR (PDR), the corresponding limitation is recurrence after treatment interruption rather than primary non-response, and these two patterns should not be conflated. This review examines translational research in DR across four domains. First, we review mechanistic work on the neurovascular unit, metabolic memory and its epigenetic substrate, the gut-retina axis, and human platforms including induced pluripotent stem cell (iPSC)-derived retinal organoids and clustered regularly interspaced short palindromic repeats (CRISPR) editing. Second, we discuss therapeutic targets beyond VEGF, including the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and related inflammatory pathways, neuroprotection, complement activation, the angiopoietin-2 (Ang2)/Tie2 axis, and non-coding RNA (ncRNA) networks. Third, in preclinical pharmacology, we regard delivery as the rate-limiting step and analyze in detail why lipid nanoparticle and N-acetylgalactosamine (GalNAc) conjugation strategies, which transformed hepatic RNA interference, have not translated to the retina, and what the terminated bevasiranib, PF-04523655, and iCo-007 programmes imply for trial design. Fourth, clinical translation, including cytokine biomarkers, artificial intelligence (AI)-based screening, combination regimens, and sustained-release implants. Evidence derived from age-related macular degeneration (AMD), including complement inhibition, stem cell transplantation, and photovoltaic implants, is evaluated separately, and its transferability to DR is assessed in light of differences in affected compartment, pathogenic driver, patient age, and expected treatment duration. We conclude that the principal obstacles in DR are no longer mechanistic but concern cell-type-specific delivery, early-phase trial design, and endpoint standardization, and we specify the evidence each candidate class should generate before clinical development proceeds.},
}

@article {pmid42924975,
year = {2026},
author = {Inferrera, L and Biscontin, A and Ajcevic, M and Accardo, A and Drigo, A and Tognetto, D and Miladinovic, A},
title = {Spatially Grounded Neurosymbolic AI for Explainable Retinal Disease Classification From OCT Images.},
journal = {Translational vision science & technology},
volume = {15},
number = {10},
pages = {36},
doi = {10.1167/tvst.15.10.36},
pmid = {42924975},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Convolutional Neural Networks ; *Retinal Diseases/classification/diagnostic imaging ; Retrospective Studies ; *Artificial Intelligence ; ROC Curve ; Retina/diagnostic imaging ; },
abstract = {PURPOSE: To develop and evaluate a spatially grounded neurosymbolic AI framework for explainable multilabel retinal disease classification from optical coherence tomography (OCT) images, integrating convolutional neural network (CNN)-based retinal sign extraction, symbolic clinical reasoning, and retinal-layer spatial information.

METHODS: Spectral-domain OCT B-scans were retrospectively collected and classified into ten categories: dry and wet age-related macular degeneration, central serous chorioretinopathy, myopic chorioretinopathy, epiretinal membrane, pseudomacular hole, lamellar macular hole, full-thickness macular hole, diabetic retinopathy, and normal retina. The model combined a CNN backbone with SegFormer-derived retinal-layer maps and mask-guided attention to estimate continuous OCT sign probabilities, which were propagated through expert-defined symbolic rules. Performance was evaluated using multilabel precision, recall, F1-score, confusion matrices, and receiver operating characteristic analysis. Inference was also performed on 402 OCT images from pathologies outside the target taxonomy.

RESULTS: Micro-average precision, recall, and F1-score were 0.91, 0.81, and 0.86, respectively; weighted-average values were 0.91, 0.81, and 0.85, and macro-average values were 0.78, 0.71, and 0.74. The micro-average AUC was 0.98. None of the 402 out-of-taxonomy pathological OCT images received a positive Normal-class prediction at the predefined 0.5 threshold.

CONCLUSIONS: The spatially grounded neurosymbolic framework provided interpretable multilabel OCT classification and showed conservative behavior on pathological images outside the modeled taxonomy. This should not be interpreted as diagnostic recognition of unseen diseases.

TRANSLATIONAL RELEVANCE: The framework may support transparent, sign-based, and anatomically grounded AI-assisted OCT interpretation.},
}

Humans
*Tomography, Optical Coherence/methods
Convolutional Neural Networks
*Retinal Diseases/classification/diagnostic imaging
Retrospective Studies
*Artificial Intelligence
ROC Curve
Retina/diagnostic imaging

@article {pmid42924995,
year = {2026},
author = {Xu, C and Yan, Q and Feng, C and Li, Y and Li, X and Zhang, R and He, J and Wu, J},
title = {Integrative Genomic Analyses Prioritize CETP-Related Lipid Traits in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {12},
pages = {54},
doi = {10.1167/iovs.67.12.54},
pmid = {42924995},
issn = {1552-5783},
mesh = {*Cholesterol Ester Transfer Proteins/genetics ; Humans ; Genome-Wide Association Study ; *Macular Degeneration/genetics/metabolism ; Genetic Predisposition to Disease ; *Cholesterol, HDL/genetics/blood ; Polymorphism, Single Nucleotide ; Mendelian Randomization Analysis ; Quantitative Trait Loci ; Disease Progression ; *Genomics/methods ; Female ; Male ; },
abstract = {PURPOSE: To characterize the genetically supported candidate gene landscape of age-related macular degeneration (AMD), identify robust candidate genes, and evaluate the potential roles of cholesteryl ester transfer protein (CETP)-related lipid traits in AMD susceptibility and progression.

METHODS: Large-scale AMD genome-wide association study discovery and replication cohorts were analyzed using an integrative framework combining single-tissue and cross-tissue transcriptome-wide association studies (TWASs) with MAGMA gene-based analysis. Candidate genes were further evaluated using GTEx expression quantitative trait loci data with summary-data-based Mendelian randomization (SMR) and colocalization analyses. Mendelian randomization (MR), multivariable MR (MVMR), and MR-Bayesian model averaging (MR-BMA) were used to assess CETP-related lipid traits in AMD risk and progression.

RESULTS: Integrated evidence from TWASs and MAGMA prioritized seven AMD-associated genes, including CFH, CETP, PLEKHA1, RDH5, HTRA1, AFF1, and ZBTB41. Two-sample MR indicated that genetically predicted CETP-related high-density lipoprotein cholesterol (HDL-C) was associated with increased AMD risk (odds ratio = 1.51; 95% confidence interval, 1.40-1.62; P = 7.0 × 10-27). In MVMR analyses, CETP-related HDL-C retained an independent association, and MR-BMA ranked it as the lipid trait with the highest posterior support. Exploratory analyses suggested that genetically predicted CETP-related HDL-C was associated with AMD progression, including choroidal neovascularization and geographic atrophy.

CONCLUSIONS: Across discovery and replication cohorts, this multi-cohort, multi-method study prioritized CETP as a genetically supported candidate effector gene for AMD and implicates HDL-C-related genetic variation at the CETP locus in AMD susceptibility and exploratory progression outcomes. These findings support the potential relevance of CETP-related lipid biology but require further mechanistic validation.},
}

*Cholesterol Ester Transfer Proteins/genetics
Humans
Genome-Wide Association Study
*Macular Degeneration/genetics/metabolism
Genetic Predisposition to Disease
*Cholesterol, HDL/genetics/blood
Polymorphism, Single Nucleotide
Mendelian Randomization Analysis
Quantitative Trait Loci
Disease Progression
*Genomics/methods
Female
Male

@article {pmid42925337,
year = {2026},
author = {Hirai, H and Kuraoka, D and Mizusawa, Y and Tsujinaka, H and Nishi, T and Kase, S},
title = {Choroidal structural changes following intravitreal injection of faricimab or aflibercept 8 mg in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42925337},
issn = {1435-702X},
abstract = {PURPOSE: To compare choroidal structural changes following the initial three injections of faricimab or high-dose (8 mg) aflibercept in eyes with neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective study included 38 eyes (comprising both treatment-naïve and switch cases) that received three consecutive intravitreal injections of either faricimab (n = 24) or aflibercept 8 mg (n = 14). Subfoveal choroidal area was manually segmented on spectral-domain optical coherence tomography and binarized using Niblack's method. The evaluated parameters were central choroidal thickness (CCT) and the luminal-to-choroidal area ratio (L/C ratio).

RESULTS: CCT significantly decreased in the aflibercept 8 mg group (P < 0.001), whereas the faricimab group showed no significant post-hoc pairwise differences. Conversely, faricimab was associated with a significant longitudinal reduction in the L/C ratio (P = 0.0011), which was evident after both the first (P = 0.022) and third injections (P = 0.0013). In contrast, the aflibercept 8 mg group showed no significant changes in the L/C ratio (P = 0.53). Consequently, changes in the L/C ratio after the third injection were significantly greater in the faricimab group than in the aflibercept 8 mg group (-1.6% vs. 0.4%, P = 0.016).

CONCLUSIONS: Aflibercept 8 mg was associated with reduced overall choroidal thickness, whereas faricimab was associated with reduced luminal choroidal proportion. These findings may indicate differences in choroidal structural changes between the two agents during the first three injections, although further studies with larger sample sizes are needed to confirm these findings.},
}

@article {pmid42925406,
year = {2026},
author = {Borkar, D and Toth, J and Balasubramanian, S and Stoelzel, M and Wolfram, J and Shortridge, E},
title = {Early Clinical Adoption and Treatment Patterns of Avacincaptad Pegol for Geographic Atrophy in the USA: An IRIS[®] Registry Analysis.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42925406},
issn = {2193-8245},
abstract = {INTRODUCTION: The US Food and Drug Administration (FDA) approved avacincaptad pegol (ACP) 2 mg in August 2023 for the treatment of geographic atrophy (GA). With limited data published on real-world use, this study evaluates patient characteristics, treatment patterns, and adverse event (AE) profiles in routine clinical care of patients with GA who received ACP 2 mg during the first year after FDA approval.

METHODS: This noninterventional cohort study of secondary use data from the American Academy of Ophthalmology IRIS[®] Registry (Intelligent Research in Sight) followed patients with GA (aged ≥ 50 years at diagnosis) who received their first ACP 2 mg injection (index date) between 1 September 2023 and 31 August 2024, until ACP discontinuation, switching to another GA treatment, loss to follow-up, or end of study.

RESULTS: A total of 10,181 patients (13,391 patient-eyes) were included. Mean age was 81.7 years and 65.6% of patients were female. Mean observational follow-up duration was 24.6 weeks (SD: 12.0). The most common ocular comorbidities at baseline were neovascular age-related macular degeneration (nAMD), choroidal neovascularization (CNV)-which overlap clinically and in coding-and cataract. Most (87.1%) patients had bilateral GA; however, 68.5% received ACP treatment in one eye. Patient-eyes received a mean of 3.7 ACP injections during follow-up (mean treatment interval, 7.0 weeks). The discontinuation rate was 8.7%. Overall, 3.6% of patients (2.9% of patient-eyes) experienced a prespecified AE newly recorded within the postinjection window (103 AEs per 10,000 ACP injections), most frequently nAMD and CNV (each < 1% of eyes).

CONCLUSIONS: This study based on secondary use data provides early insights into ACP 2 mg treatment patterns in patients with GA treated in routine clinical practice within the USA during the first year after approval. Plain Language Summary Geographic atrophy is an advanced form of age-related macular degeneration affecting vision. Over time people with geographic atrophy will lose their vision. The Food and Drug Administration (FDA) in the USA approved avacincaptad pegol (ACP) in August 2023 to treat people with geographic atrophy. In this study, researchers looked at medical records from people with geographic atrophy stored anonymously in the American Academy of Ophthalmology IRIS[®] Registry (Intelligent Research in Sight). This study looked at how ACP was used in the real world in US clinics and what health events occurred after treatment. People aged 50 years or older with a confirmed diagnosis of GA were included. They must have had their first treatment with ACP between 1 September 2023 and 21 August 2024. This time period is the first year of ACP approval. A total of 10,181 people with geographic atrophy were included. The results of this study showed that on average, ACP was injected every 7 weeks in the eye and that most people received it in one eye. Few people stopped ACP (8.7%) or switched to another treatment (3.3%). Health events following treatment occurred in 3.6% of people. The results of this study provide early information on how ACP is being used in the real world in US clinical practice.},
}

@article {pmid42926416,
year = {2026},
author = {Gogna, N and Collin, GB and Hyde, LF and Stone, L and Pandey, R and Kennedy, VE and Krebs, MP and Naggert, JK and Nishina, PM},
title = {A new mouse model for a high-risk AMD variant, ARMS2 [A69S].},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.10.02.756275},
pmid = {42926416},
issn = {2692-8205},
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible central vision loss in older adults. The highest genetic risk for AMD maps to Chromosome 10q26. However, due to strong linkage disequilibrium between two genes, ARMS2 and HTRA1 located in this region, it has been difficult to determine whether one or both genes contribute to the AMD-disease risk. Functional studies of ARMS2 have been hampered due to the lack of animal models, as orthologs are only found in the higher primates and the gene is absent in rodents. To model ARMS2 biology in vivo , we used CRISPR-Cas9 to insert the complete human ARMS2 gene carrying the A69S risk variant (rs10490924), into a region of homology between humans and mice, on mouse Chromosome 7, 3.5 kb upstream of Htra1 , preserving its native promoter, spacing, and orientation. We also generated a mouse model bearing its wild-type counterpart ARMS2 [A69] (ARMS2 [WT]). RNA analysis revealed tissue- and cell-type-specific patterns of ARMS2 expression with enrichment in neural tissues, testis, and eye, and within the eye, in retinal horizontal cells and the retinal pigment epithelium (RPE). ARMS2 expression was consistent with human expression data and unaltered by the A69S mutation. By 12 months of age, ARMS2 [A69S] mice developed AMD-relevant phenotypes including increased fundus spots, A69S-specific thinning of the outer nuclear layer, and reduced scotopic ERG amplitudes. Transcriptomic profiling of postnatal day 14 retina and RPE-enriched fractions revealed reduced mitochondrial oxidative-phosphorylation genes, corroborated by reduced retinal mtDNA copy number and lower maximal respiration, alongside preliminary results that suggest sphingolipid remodeling in the RPE. This humanized model links the ARMS2 A69S variant to mitochondrial dysfunction and provides an in vivo platform for defining AMD mechanisms and testing therapies.},
}

@article {pmid42926478,
year = {2026},
author = {Bhuckory, MB and Mamchik, V and Ly, K and Jensen, N and Shautsova, V and Devaud, Q and Shin, A and Pham-Howard, D and Dalal, R and Galambos, L and Kamins, T and Palanker, D},
title = {Biomimetic scaffolds mimic human subretinal debris for preclinical testing of prosthetic vision.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.10.06.756601},
pmid = {42926478},
issn = {2692-8205},
abstract = {Photovoltaic subretinal prostheses replace the lost photoreceptors in patients blinded by atrophic age-related macular degeneration (AMD) and provide central vision by electrically stimulating the inner retinal neurons. Subretinal debris in geographic atrophy separate the inner nuclear layer from the implant by tens of micrometers, increasing the stimulation threshold and reducing the pattern contrast. Absence of this separating layer in animal models diminishes the accuracy of preclinical testing of the next-generation implants, especially with smaller pixels. We developed three-dimensional biomimetic scaffolds nanoprinted onto photovoltaic arrays to provide a precisely controlled separation between the implants and target neurons in animal models of retinal degeneration. Gap sizes of the scaffolds were adjusted to meet the following requirements: they should allow light penetration to the implant, provide unobstructed flow of electric current, but preclude migration of cells into their 3-D structure. Gaps of 3 µm were found to be optimal as they restricted cellular migration and maintained the inner nuclear layer above both planar and pillar electrode arrays. Scaffolds did not measurably alter the photovoltaic response and accurately reproduced the distance dependence of stimulation threshold. Following implantation, the initially fluid-filled intra-scaffold space was progressively filled by cellular matter matching the density of the subretinal debris. This transition is expected to increase resistivity of the scaffold to that of tissue, which was evidenced by concurrently improved grating acuity. These results establish a model of the controlled separation between the implant and the target neurons reproducing the features of subretinal debris in geographic atrophy of human patients, thereby providing a platform for accurate preclinical evaluation of the subretinal implants.},
}

@article {pmid42926582,
year = {2026},
author = {Wells, BL and Filiberti, A and Stanford, DR and Pham, KD and Walton, DA and Plafker, SM and Freeman, WM and Chucair-Elliott, AJ},
title = {Functional and molecular profiles of the neuroretina and retinal pigmented epithelium-choroid in response to aging and Nrf2 deletion.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.10.08.757667},
pmid = {42926582},
issn = {2692-8205},
abstract = {PURPOSE: Age is the leading factor for age-related macular degeneration (AMD), in which retinal pigmented epithelium (RPE) atrophy is a hallmark. The nuclear factor-erythroid 2-related factor 2 (Nrf2), a major anti-stress transcription factor, decreases in AMD, suggesting bioenergetic stress interacts with age during AMD pathogenesis. We profiled visual function and gene expression of the retina and RPE-choroid with Nrf2 deletion and aging.

METHODS: We tested 3mo and 14mo Nrf2 null (Nrf2 KO) and Nrf2 WT mice for optokinetic tracking (OKT) and dark-adapted electroretinography (ERG) responses. Eyes were harvested for retina outer nuclear layer (ONL) thickness analysis and retina and RPE-choroid cup RNA isolation for RNAseq profiling.

RESULTS: Visual acuity was reduced with aging with lower values in the Nrf2 KO vs Nrf2 WT comparison at 14mo. We observed aged-related reduction of a-, b-, and c-wave ERG amplitudes in both WT and KO mice. Age-related c-wave decline was exacerbated by Nrf2 loss. By RNAseq, two-way ANOVA of RPE-choroid samples revealed differentially expressed genes (DEGs) with age and genotype main effects, as well as DEGs with age and genotype interaction effects. Age DEGs were over-represented in pathways related to inflammation and phagocytosis. Genotype DEGs were associated with alterations in antioxidant and inflammatory processes. Retina RNAseq showed age and genotype DEGs.

CONCLUSIONS: Ablation of Nrf2 exacerbates age-related declines suggesting that decrease in Nrf2 with aging has functional consequences for inflammation/resiliency. We provide retina and RPE-choroid bulk-RNAseq datasets from the same cohort of mice that can be interrogated to better understand degeneration of retina/RPE-choroid.},
}

@article {pmid42926601,
year = {2026},
author = {Zhu, S and Puja, A and McNeel, R and Alabdallat, D and Ngo, T and Du, J},
title = {Aging Differentially Remodels the Retina and RPE/Choroid Proteome and Metabolism.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.10.07.757409},
pmid = {42926601},
issn = {2692-8205},
abstract = {PURPOSE: The neural retina and retinal pigment epithelium/choroid (RPE/Cho) are metabolically coupled. Metabolic dysfunction of the RPE/Cho contributes to photoreceptor death in age-related macular degeneration (AMD). This study aimed to determine how aging, a major risk factor for AMD, alters the proteome and metabolic pathways in the retina and RPE/Cho.

METHODS: We performed quantitative proteomics on neural retina and RPE/Cho from young (8-week) and old (73-week) C57BL/6J mice. The differentially expressed proteins between old and young, as well as between the retina and RPE/Cho, were visualized using volcano plots and heatmaps, and functional analyses were assessed by Gene Ontology enrichment tools.

RESULTS: Aging altered the expression of 85 retinal proteins and 272 RPE/Cho, with 16 shared between tissues. In the aged retina, proteins associated with NADP(H) metabolism, neurodegeneration, and immunity were mostly upregulated, while proteins in lipid metabolism, transcription, and epigenetic regulation decreased. In the aged RPE/Cho, all 21 significantly altered lysosomal enzymes and transport proteins increased, together with complement components, and photoreceptor outer segment proteins. These changes accompanied increases in proteins associated with lipid metabolism and protection against lipid peroxidation, while several glutathione metabolism enzymes decreased. Seven shared proteins involved in lipid and NADP(H) metabolism, changed in opposite directions between retina and RPE/Cho. Comparison of the retinal and RPE/Cho proteomes identified 3073 differentially abundant proteins, of which 2452 maintained tissue-specific differences across both age groups, while approximately 17% showed age-dependent shifts in tissue enrichment. These shifts involved proteins associated with metabolism, extracellular matrix, visual function, lysosomal pathways, and innate immunity. Within the metabolic proteome, several glycolytic and fatty acid oxidation proteins showed greater relative enrichment in RPE/Cho with age, whereas glucose transporters and mitochondrial complexes shifted toward the retina.

CONCLUSIONS: Overall, these findings show that aging differentially remodels the retina and RPE/Cho proteome, accompanied by altered metabolic specialization between the two tissues.},
}

@article {pmid42911703,
year = {2026},
author = {Besztercei, B and Antal, R and Tähtivaara, L and Lappeteläinen, B and Jääskeläinen, N and Szappanos, A and Lukáts, Á and Pál-Kajtár, A and Budai, A and Marton, AD and Stifter-Mursits, M and Hiripi, L and Balogh, GT and Cerrada-Gimenez, M and Kovács, KA},
title = {Three Nitrogen Atoms Turn Old Kinase Inhibitors Into New Targetable Remedy.},
journal = {Journal of medicinal chemistry},
volume = {69},
number = {20},
pages = {23790-23809},
doi = {10.1021/acs.jmedchem.6c01380},
pmid = {42911703},
issn = {1520-4804},
support = {101047120//HORIZON EUROPE European Innovation Council/ ; },
mesh = {Animals ; Humans ; *Protein Kinase Inhibitors/pharmacology/chemistry/therapeutic use/chemical synthesis ; *Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors/metabolism ; Rats ; Mice ; Choroidal Neovascularization/drug therapy ; Structure-Activity Relationship ; Green Light ; },
abstract = {Pathological neovascularization in the eye is a significant contributor to vision loss in diseases such as age-related macular degeneration and diabetic retinopathy. While anti-VEGF biologics are effective, they require repeated intravitreal injections. Here, we report a novel principle for designing photoactivatable VEGFR2 inhibitors, along with two examples, EYE1090 and EYE1118. Azido-functionalization in these molecules enables light-triggered receptor binding while preserving potent inhibition in the dark. Both compounds exhibit significantly enhanced activity upon exposure to green light that reaches the human retina, also in the elderly. In vitro, the compounds robustly inhibited angiogenesis and endothelial migration that was further potentiated by light. In vivo, orally administered EYE1090 and EYE1118 suppressed VEGF-induced retinal leakage in rats and reduced lesion size in a mouse model of choroidal neovascularization, but did not show acute hepatotoxicity. Our findings introduce a novel light-targeted pharmacological approach exploiting the natural light focusing anatomy of the eye.},
}

Animals
Humans
*Protein Kinase Inhibitors/pharmacology/chemistry/therapeutic use/chemical synthesis
*Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors/metabolism
Rats
Mice
Choroidal Neovascularization/drug therapy
Structure-Activity Relationship
Green Light

@article {pmid42911836,
year = {2026},
author = {Emre, T and Chakravarty, A and Pinetz, T and Lachinov, D and Menten, MJ and Scholl, H and Sivaprasad, S and Rueckert, D and Lotery, A and Sacu, S and Schmidt-Erfurth, U and Bogunovic, H},
title = {Stochastic Siamese MAE Pretraining for Longitudinal Medical Images.},
journal = {IEEE transactions on medical imaging},
volume = {PP},
number = {},
pages = {},
doi = {10.1109/TMI.2026.3745973},
pmid = {42911836},
issn = {1558-254X},
abstract = {Temporally aware image representations are crucial for capturing disease progression in 3D volumes of longitudinal medical datasets. However, recent state-of-the-art self-supervised learning approaches like Masked Autoencoding (MAE), despite their strong representation learning capabilities, lack temporal awareness. In this paper, we propose STAMP (Stochastic Temporal Autoencoder with Masked Pretraining), a Siamese MAE framework that encodes temporal information through a stochastic process by conditioning on the time difference between the 2 input volumes. Unlike deterministic Siamese approaches, which compare scans from different time points but fail to account for the inherent uncertainty in disease evolution, STAMP learns temporal dynamics stochastically by reframing the MAE reconstruction loss as a conditional variational inference objective. We evaluated STAMP on two OCT and one MRI datasets with multiple visits per patient. STAMP pretrained ViT models outperformed both existing temporal MAE methods and foundation models on different late stage Age-Related Macular Degeneration and Alzheimer's Disease progression prediction which require models to learn the underlying non-deterministic temporal dynamics of the diseases.},
}

@article {pmid42912071,
year = {2026},
author = {Dias, JGDS and Andrade, GC and Macedo, JVTL and Graziano, AS},
title = {Fundus camera and artificial intelligence for diabetic retinopathy screening in a São Paulo shelter.},
journal = {Revista da Associacao Medica Brasileira (1992)},
volume = {72},
number = {9},
pages = {e20260862},
pmid = {42912071},
issn = {1806-9282},
mesh = {Humans ; *Diabetic Retinopathy/diagnostic imaging/diagnosis ; Male ; Aged ; Female ; Prospective Studies ; Pilot Projects ; Brazil ; *Artificial Intelligence ; Sensitivity and Specificity ; *Smartphone ; *Photography/instrumentation/methods ; Mass Screening/methods ; Fundus Oculi ; Reproducibility of Results ; Aged, 80 and over ; Middle Aged ; },
abstract = {OBJECTIVE: The aim of this study was to evaluate the applicability of a smartphone-based portable fundus camera for diabetic retinopathy screening in elderly residents of a specialized shelter in São Paulo, Brazil, considering image acquisition by non-ophthalmologist professionals and remote case classification.

METHODS: Prospective pilot interventional study at the Centro de Acolhida Especial para Idosos Morada São João. Thirty-eight participants (76 eyes) underwent retinal imaging using the Eyer® portable fundus camera (Phelcom Technologies, Brazil) by trained non-ophthalmologist professionals. Images were remotely evaluated by a retinal specialist and compared to the EyerMaps® artificial intelligence system.

RESULTS: Mean age was 71.6±7.0 years; 78.9% male. Fifteen participants (39.5%) had confirmed diabetes mellitus. The specialist identified abnormalities in 70 of 76 eyes (92.1%), most frequently glaucoma suspicion, media opacity suggestive of cataract, chorioretinal changes, and age-related macular degeneration signs; no diabetic retinopathy was identified. Against the specialist's assessment of any ocular abnormality as the reference standard, the artificial intelligence system classified 22 eyes as abnormal, yielding sensitivity 25.7% (95%CI 16.9-37.0), specificity 33.3% (95%CI 9.7-70.0), positive predictive value 81.8% (95%CI 61.5-92.7), negative predictive value 3.7% (95%CI 1.0-12.5), and overall accuracy 26.3% (95%CI 17.7-37.2).

CONCLUSION: The Eyer® device demonstrated operational feasibility for ocular screening by trained non-ophthalmologists. The high prevalence of media opacities and non-diabetic retinopathy conditions compromised artificial intelligence performance, highlighting the need for broader screening strategies in elderly and socially vulnerable populations.},
}

Humans
*Diabetic Retinopathy/diagnostic imaging/diagnosis
Male
Aged
Female
Prospective Studies
Pilot Projects
Brazil
*Artificial Intelligence
Sensitivity and Specificity
*Smartphone
*Photography/instrumentation/methods
Mass Screening/methods
Fundus Oculi
Reproducibility of Results
Aged, 80 and over
Middle Aged

@article {pmid42918418,
year = {2026},
author = {Goerdt, L and Bessaheken, D and Terheyden, JH and Thiele, S and Basten, V and Behning, C and Luhmann, U and Leal, S and Moll, KP and Zakaria, N and Schmid, M and Finger, RP and Holz, FG and Schmitz-Valckenberg, S and Saßmannshausen, M and , },
title = {Longitudinal analysis of structural biomarkers for disease progression in intermediate age-related macular degeneration: a MACUSTAR study report.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.10.005},
pmid = {42918418},
issn = {2468-6530},
abstract = {PURPOSE: To investigate the prognostic impact of qualitative and quantitative structural biomarkers including their topographic distribution for progression to geographic atrophy (GA) or neovascular age-related macular degeneration (nAMD) in eyes with intermediate AMD (iAMD) within the longitudinal part of the MACUSTAR study (NCT03349801).

DESIGN: Longitudinal, prospective low-interventional European multicenter cohort study.

SUBJECTS: 577 eyes of 577 study patients with iAMD.

METHODS: Study eyes with iAMD underwent multimodal retinal imaging at each study visit followed by a standardized grading of structural biomarkers, including presence of subretinal drusenoid deposits (SDDs), vitelliform lesion, pigmentary abnormalities (PAs), refractile deposits, pigment epithelium detachment (PED), non-exudative choroidal neovascularization (nCNV), incomplete (i) retinal pigment epithelium and outer retinal atrophy (RORA), complete (c) RORA, and hyperreflective foci presence (HRF). Automated assessment of the retinal pigment epithelium drusen complex (RPEDC) volume and HRF area including their topographic distribution based on spectral-domain optical coherence tomography (OCT) imaging was conducted using a deep-learning based algorithm. Disease progression (GA/nAMD) was assessed at each study visit up to a follow-up time of 4 years. Multivariable time-discrete hazard models were used to evaluate the biomarkers' relevance for disease progression in the entire OCT volume, the central 3 mm disk, and the central subfield of the Early Treatment Diabetes Retinopathy Study (ETDRS) Grid.

MAIN OUTCOME MEASURES: Disease progression to GA/nAMD, hazard ratios of structural biomarkers for disease progression RESULTS: A total of 577 study eyes of 577 iAMD study patients (mean age 72.01 ± 7.01 years, 66.1 % female, median follow-up 3 years) were included. Disease progression was detected in 82 eyes (9.01 %), 37 (6.4 %) progressed to GA, and 45 (7.7 %) to nAMD. Inside the central 3 mm presence of SDDs, PED, nCNV and cRORA conferred overall risk for progression, whereas PAs, RPEDC volume, iRORA, cRORA were associated with risk for progression to GA. Only nCNV volume increased risk for nAMD.

CONCLUSIONS: Structural biomarkers indicate risk for iAMD progression and may differentiate eyes progressing to GA from eyes progressing to nAMD. Biomarker topography impacts their prognostic relevance and needs to be considered in clinical trial design.},
}

@article {pmid42920111,
year = {2026},
author = {Hsu, CH and Chen, AI and Lai, CH and Chen, NN},
title = {Progressive intraocular inflammation with anterior scleritis following intravitreal Faricimab for neovascular age-related macular degeneration: a case report.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42920111},
issn = {1471-2415},
mesh = {Humans ; Male ; *Scleritis/chemically induced/diagnosis/drug therapy ; Aged ; Intravitreal Injections ; *Angiogenesis Inhibitors/adverse effects ; *Wet Macular Degeneration/drug therapy ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; Disease Progression ; *Uveitis, Anterior/chemically induced ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: To report a rare and instructive case of intraocular inflammation following intravitreal Faricimab (Vabysmo) injection that progressed to anterior scleritis despite early intervention. While Faricimab is widely used for neovascular age-related macular degeneration (nAMD), understanding its potential for delayed, progressive inflammatory complications is crucial for clinical vigilance.

CASE PRESENTATION: A 74-year-old Asian male with nAMD developed intraocular inflammation following his fifth intravitreal injection of Faricimab, after four prior uneventful injections. The patient initially presented with corneal edema, anterior uveitis, and elevated intraocular pressure (IOP). Although initial treatment with topical corticosteroids and IOP-lowering agents led to partial improvement, the inflammation subsequently progressed, manifesting as persistent vitritis and the development of anterior scleritis. Escalation to systemic corticosteroid therapy was required, which resulted in complete resolution of the inflammation. Faricimab was permanently discontinued, and the patient was successfully switched to Aflibercept (Eylea) without further complications.

CONCLUSIONS: This case highlights that initially mild anterior segment inflammation following Faricimab injection can progress to more severe ocular inflammation, such as scleritis, despite early topical therapy. Clinicians should maintain close monitoring and a low threshold for escalating to systemic treatment to achieve complete resolution and safeguard visual outcomes.},
}

Humans
Male
*Scleritis/chemically induced/diagnosis/drug therapy
Aged
Intravitreal Injections
*Angiogenesis Inhibitors/adverse effects
*Wet Macular Degeneration/drug therapy
Receptors, Vascular Endothelial Growth Factor/therapeutic use
Disease Progression
*Uveitis, Anterior/chemically induced
Antibodies, Bispecific

@article {pmid42922246,
year = {2026},
author = {Salducci, M and Simonelli, MS and Raimondi, R and Di Meglio, M},
title = {Occupational sun exposure and dry maculopathy and/or cataract in two Italian coastal populations with high solar irradiance: a 2026 comparative observational study between Ischia and the coastal areas south of Livorno.},
journal = {La Clinica terapeutica},
volume = {177},
number = {6},
pages = {1727-1730},
doi = {10.7417/CT.2026.2177},
pmid = {42922246},
issn = {1972-6007},
mesh = {Humans ; *Sunlight/adverse effects ; Italy/epidemiology ; *Cataract/epidemiology/etiology ; Middle Aged ; Cross-Sectional Studies ; Male ; Adult ; *Occupational Exposure/adverse effects ; *Occupational Diseases/epidemiology/etiology ; *Geographic Atrophy/epidemiology/etiology ; Prevalence ; Female ; },
abstract = {BACKGROUND: Occupational solar radiation exposure represents a recognized risk factor for several ocular disorders, particularly cataract formation, while its relationship with age-related macular degeneration (AMD) remains incompletely understood.

OBJECTIVE: To compare the prevalence of lens abnormalities and dry age-related macular degeneration in two populations of outdoor coastal workers chronically exposed to solar radiation and to explore the possible association between long-term occupational sun exposure and ocular alterations.

METHODS: A cross-sectional comparative observational study was conducted between June and July 2026 in two Italian coastal populations characterized by high environmental solar irradiance: Ischia Island (n = 68) and the coastal area south of Livorno (n = 72). Eligible participants were fishermen, sailors, mooring operators and lifeguards aged 41-50 years with at least 10 years of occupational outdoor activity during peak daylight hours. Ophthalmological assessment included visual acuity testing, Amsler grid examination, anterior segment biomicroscopy and fundus evaluation.

RESULTS: No mature cataracts were identified. Lens abnormalities compatible with incipient cataract or lens sclerosis were observed in 81.81% of workers from Ischia and 79.86% of workers from the Livorno coastal area. Dry maculopathy was identified in a limited number of participants, and no statistically significant differences were observed between the two populations.

CONCLUSIONS: The findings suggest a high prevalence of early lens changes among workers occupationally exposed to prolonged solar radiation in marine environments. Although no difference emerged between the two study populations, the results support the need for preventive occupational eye health measures and further longitudinal investigations.},
}

Humans
*Sunlight/adverse effects
Italy/epidemiology
*Cataract/epidemiology/etiology
Middle Aged
Cross-Sectional Studies
Male
Adult
*Occupational Exposure/adverse effects
*Occupational Diseases/epidemiology/etiology
*Geographic Atrophy/epidemiology/etiology
Prevalence
Female

@article {pmid42906115,
year = {2026},
author = {Adam, MK and Jain, M and Kim, E and Shah, B and Crowley, A and Lee, J and Chi, GC},
title = {Clustering and Treatment Patterns in Neovascular Age-related Macular Degeneration and Diabetic Macular Edema: US Claims Database Study.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-10},
doi = {10.3928/23258160-20260818-01},
pmid = {42906115},
issn = {2325-8179},
abstract = {This study evaluated ophthalmic health care utilization patterns among United States patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) using Medicare, Medicaid, and commercial health care claims from July 1, 2016, to July 31, 2020. Patients aged ≥ 50 years for nAMD or ≥ 18 years for DME with ≥ 1 diagnosis record and ≥ 1 anti-VEGF intravitreal injection, and continuous enrollment in medical and pharmacy plans for ≥ 6 months before and ≥ 24 months after the first injection were included. Descriptive summaries and unsupervised machine-learning cluster analysis were conducted based on treatment frequency, intervals, monitoring visits, and corticosteroid use (DME only). Three clusters for nAMD and DME were identified, representing varying treatment intensities from high to low. The differing cluster characteristics suggest that socioeconomic status, comorbidities, and insurance type may be related to treatment utilization and highlight potential real-world disparities in ophthalmic health care.},
}

@article {pmid42906861,
year = {2026},
author = {Li, X and Yan, R and Huang, Y and Yu, W},
title = {Subretinal fibrosis in neovascular age-related macular degeneration: From clinical features to fibrotic mechanisms and therapeutic opportunities.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.10.007},
pmid = {42906861},
issn = {1879-3304},
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible central vision loss worldwide. Although intravitreal anti-vascular endothelial growth factor therapy has substantially improved short-term outcomes, long-term vision is frequently limited by the development of subretinal fibrosis. This progressive scarring process occurs in a substantial proportion of patients and represents a major determinant of permanent visual impairment during long-term follow-up. Subretinal fibrosis arises from a complex interaction among structural injury, inflammatory signaling, and cellular reprogramming. Clinical and imaging characteristics are associated with fibrotic progression. Experimental studies have also provided insights into the underlying biological mechanisms. To organize heterogeneous evidence across clinical, cellular, and experimental studies, this review adopts a dual-axis framework as a working model for subretinal fibrosis in nAMD. The injury-inflammation axis describes processes that establish and maintain a persistent profibrotic microenvironment, whereas the cellular reprogramming axis describes phenotypic transitions of retinal and immune cell types, including epithelial-mesenchymal transition in retinal pigment epithelium cells, macrophage-to-myofibroblast transition, endothelial and pericyte plasticity, and glial remodeling, that may generate or contribute to extracellular matrix -producing effector cell populations. These axes' crosstalk through secretory signaling and matrix-dependent mechanical feedback may contribute to the persistence of fibrotic remodeling. Emerging therapeutic approaches include interventions targeting inflammatory pathways, fibrogenic signaling, and maladaptive cellular reprogramming, including transitions toward mesenchymal and matrix-producing phenotypes, as well as gene-based and bioengineered delivery strategies. This working model may help organize current evidence, identify unresolved causal links, and inform stage-specific therapeutic strategies.},
}

@article {pmid42906862,
year = {2026},
author = {Mai, S and Chen, J and Li, B and Sun, X and Yu, X},
title = {Peripheral exudative hemorrhagic chorioretinopathy: A comprehensive review of clinical features, differential diagnosis, pathogenesis-related disease spectra, and management.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.10.011},
pmid = {42906862},
issn = {1879-3304},
abstract = {Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a peripheral chorioretinopathy characterized by retinal pigment epithelium detachment with either blood, exudation, or both, and may present with macular hemorrhage, macular exudation, and vitreous hemorrhage. PEHCR exhibits a variety of features on fundus fluorescein angiography, indocyanine green angiography, and ultrasound examinations. The hemorrhagic type PEHCR may greatly resemble malignant melanoma, whereas the exudative type can mimics primary vitreoretinal lymphoma making differential diagnosis of great importance. The pathogenesis may involve choroidal neovascularization. Early studies suggested a link to age-related macular degeneration, while subsequent research has revealed a close association with polypoidal choroidal vasculopathy and pachychoroid disease spectrum. Most cases of PEHCR are self-limiting and may be observed alone. For those complicated by, or at risk of, macular exudation, macular hemorrhage, as well as vitreous hemorrhage, management strategies include intravitreal anti-vascular endothelial growth factor injections, vitrectomy, laser photocoagulation, photodynamic therapy, and cryotherapy.},
}

@article {pmid42907641,
year = {2026},
author = {Njoku, VT and Metaliaj, A and Darie, CC and Blenkinsop, T and Radu, A},
title = {Proteomics Approaches Used to Investigate Age Related Macular Degeneration.},
journal = {Advances in experimental medicine and biology},
volume = {1359},
number = {},
pages = {329-342},
pmid = {42907641},
issn = {0065-2598},
mesh = {*Proteomics/methods ; Humans ; *Macular Degeneration/metabolism/diagnosis ; Biomarkers/metabolism/analysis ; Mass Spectrometry/methods ; *Eye Proteins/metabolism/analysis ; Animals ; *Proteome/metabolism ; },
abstract = {Age-related macular degeneration (AMD) affects a very large proportion of the elderly population, leading to progressive loss of vision. For the most frequent form of the disease, dry AMD, no effective therapies exist. This is a consequence of the fact that the mechanisms that lead to dry AMD are not understood. Among the many strategies used to accomplish this unmet need, valuable insights were provided by proteomics studies of biological fluids and of the eye cells affected by the disease. We review here the proteomics methods used by these studies, compare their advantages and limitations, and present the biologically relevant information produced by each method. We emphasize that proteomics methods continue to have high potential for this research area and are expected to lead to substantial progress towards understanding and curing AMD.},
}

*Proteomics/methods
Humans
*Macular Degeneration/metabolism/diagnosis
Biomarkers/metabolism/analysis
Mass Spectrometry/methods
*Eye Proteins/metabolism/analysis
Animals
*Proteome/metabolism

@article {pmid42908726,
year = {2026},
author = {Janetos, TM and Rivera, AS and Li, Y and Andrews, CA and Bryar, PJ and Gill, MK and Lavine, JA and Stein, JD and French, DD and , and , },
title = {Social Determinants of Health, Vision, and Treatment in Exudative Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {11},
pages = {101409},
pmid = {42908726},
issn = {2666-9145},
abstract = {PURPOSE: Treatment deviations in exudative age-related macular degeneration (exAMD) are common and lead to worse visual outcomes; reasons remain incompletely understood. We sought to identify distinct treatment patterns in newly diagnosed, treatment-naïve exAMD and to evaluate associations with social determinants of health (SDH) and baseline vision.

DESIGN: Multicenter retrospective cohort study.

PARTICIPANTS: A total of 15 664 newly diagnosed, treatment-naïve exAMD patients receiving at least one intravitreal injection between January 1, 2014 and January 1, 2024 across 17 academic medical centers in the Sight Outcomes Research Collaborative ophthalmology big data repository.

METHODS: Treatment patterns over the first 12 months were grouped using sequence clustering. Mixed-effects logistic regression evaluated associations between cluster membership and sex, age, race and ethnicity, primary language, urbanicity, primary insurance, distressed communities index, Charlson comorbidity index, and baseline logarithm of the minimum angle of resolution visual acuity.

MAIN OUTCOME MEASURES: Sequence-derived treatment cluster membership and its association with SDH and baseline vision.

RESULTS: Two clusters were identified: "frequent treatment" (67.4%) and "nonpersistent" (32.6%); the latter characterized by a few initial injections followed by early treatment cessation. Nonpersistence was best differentiated by ≥ 7 months without an office visit or treatment (Youden index, 0.83; area under the curve, 0.93). In the adjusted model, factors associated with nonpersistent cluster membership included Black race (adjusted odds ratio [aOR], 1.42; 95% confidence interval [CI], 1.11-1.80), Hispanic ethnicity (aOR, 1.38; 95% CI, 1.00-1.90), older age at index date (aOR, 1.08 per decade; 95% CI, 1.03-1.13), rural residence (aOR, 1.32; 95% CI, 1.11-1.58), increasing distressed communities index (aOR, 1.03; 95% CI, 1.01-1.05), Medicaid insurance (aOR, 1.62; 95% CI, 1.03-2.52), worse baseline logarithm of the minimum angle of resolution acuity (aOR, 1.71 per unit; 95% CI, 1.54-1.91), and lower Charlson comorbidity index (aOR, 0.95 per point; 95% CI, 0.93-0.97).

CONCLUSIONS: Demographics, SDH, and vision were associated with nonpersistence in newly diagnosed exAMD. Social determinants of health‑informed identification of high-risk individuals may guide qualitative work on modifiable barriers and intervention development to prevent irreversible vision loss.

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

@article {pmid42910810,
year = {2026},
author = {Pawloff, M and Hollaus, M and Schwarzenbacher, L and Weigert, G and Baratsits, M and Sacu, S and Ritter, M and Reiter, GS},
title = {Quantitative Fundus Autofluorescence in Geographic Atrophy Secondary to AMD: Comparison With Stargardt Disease, PRPH2-Associated Retinal Dystrophies, and Healthy Controls.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {12},
pages = {50},
doi = {10.1167/iovs.67.12.50},
pmid = {42910810},
issn = {1552-5783},
mesh = {Humans ; Female ; *Geographic Atrophy/etiology/diagnosis ; *Stargardt Disease ; Cross-Sectional Studies ; Male ; Middle Aged ; Fundus Oculi ; *Macular Degeneration/complications/congenital/diagnosis ; *Peripherins/genetics/metabolism ; Aged ; Ophthalmoscopy ; Fluorescein Angiography/methods ; *Retinal Dystrophies/diagnosis/genetics ; Tomography, Optical Coherence/methods ; Adult ; Visual Acuity ; },
abstract = {PURPOSE: To analyze differences in quantitative fundus autofluorescence (qAF) between geographic atrophy (GA) secondary to age-related macular degeneration (AMD) and other diseases associated with macular atrophy including Stargardt disease (STGD), and autosomal-dominant PRPH2-associated retinal dystrophies (PRPH2).

METHODS: Patients with GA, STGD, PRPH2, and healthy subjects were included in this cross-sectional study. The qAF was assessed using a confocal scanning laser ophthalmoscope equipped with an internal fluorescent reference. Mean qAF values were obtained using the standardized qAF Delori pattern (qAF8). Care was taken to remove areas of atrophy within the qAF8 pattern. Mixed models were calculated to compare disease groups, correcting for age, and evaluate possible associations between qAF8 and macular atrophy size.

RESULTS: Two hundred eight eyes from 118 patients (87 GA, 22 STGD, 10 PRPH2, 89 healthy controls) were analyzed. There were significant differences in qAF8 between the groups (P < 0.001). GA patients showed significantly reduced qAF8 values compared to healthy controls (P < 0.001), STGD patients (P < 0.001), and PRPH2 patients (P < 0.001). STGD patients demonstrated significantly elevated qAF8 values compared to healthy controls (P < 0.001). PRPH2 patients did not differ from healthy controls (P = 0.3). GA and PRPH2 demonstrated nominal inverse correlations with increasing atrophy area, whereas STGD showed a significant positive correlation. Lens status was confounded completely with disease group and thus could not be tested as an independent covariate. Univariately, lens status was associated with qAF8 (P < 0.001), whereas age was not significant in the final model (P = 0.4).

CONCLUSIONS: The qAF8 varies significantly between eyes with macular atrophy due to GA secondary to AMD, STGD and PRPH2-associated retinal dystrophy. Although age was included as covariate, residual confounding cannot entirely be excluded due to the partial overlap in age distributions of cohorts. Lens status could not be adjusted for because it was completely confounded with disease group. This noninvasive, objectively acquired data may serve as an adjunctive biomarker to support diagnosis, prognosis, counselling and management in these degenerative disorders, pending further validation in balanced cohorts.},
}

Humans
Female
*Geographic Atrophy/etiology/diagnosis
*Stargardt Disease
Cross-Sectional Studies
Male
Middle Aged
Fundus Oculi
*Macular Degeneration/complications/congenital/diagnosis
*Peripherins/genetics/metabolism
Aged
Ophthalmoscopy
Fluorescein Angiography/methods
*Retinal Dystrophies/diagnosis/genetics
Tomography, Optical Coherence/methods
Adult
Visual Acuity

@article {pmid42911482,
year = {2027},
author = {Savickyte, I and Lapinaite, A},
title = {Role of Chromatin-Associated RNAs in Eye Physiology and Pathology.},
journal = {Methods in molecular biology (Clifton, N.J.)},
volume = {3091},
number = {},
pages = {1-46},
pmid = {42911482},
issn = {1940-6029},
mesh = {Humans ; *Chromatin/genetics/metabolism ; Animals ; *Eye Diseases/genetics/metabolism/pathology ; *RNA, Untranslated/genetics ; Gene Expression Regulation ; *Eye/metabolism/pathology/physiopathology ; CRISPR-Cas Systems ; Epigenesis, Genetic ; Retinal Pigment Epithelium/metabolism ; },
abstract = {Noncoding RNAs, including long noncoding RNAs, enhancer RNAs, circular RNAs, and small nuclear and nucleolar RNAs, represent a major, yet still largely uncharacterized, regulatory layer in the eye. A subset of these molecules, chromatin-associated RNAs (caRNAs), physically interacts with DNA and nuclear protein complexes to influence genome organization, transcriptional output, and stress responses. Although caRNAs have emerged as essential regulators of chromatin topology and gene expression in diverse tissues, their identity, dynamics, and mechanisms in the retina and retinal pigment epithelium (RPE) remain elusive. Recent high-resolution genomic studies, disease transcriptomes, and mechanistic studies implicate dysregulated caRNAs in age-related macular degeneration, glaucoma, and diabetic retinopathy, yet causal chromatin-level functions have rarely been demonstrated. In this review, we summarize current understanding of ncRNA-mediated regulation in vision, highlight emerging evidence for caRNA involvement in retinal development, photoreceptor and RPE specialization, and disease-associated epigenetic remodeling, and outline major mechanistic gaps that must be addressed. We then survey the rapidly expanding CRISPR toolbox, including base and prime editors, CRISPRi/a, Cas13 knockdown and editing platforms, and RNA-recruitment and spatial repositioning systems, that now enable targeted perturbation of both caRNA genomic loci and transcripts. These technologies provide the first practical route to move beyond correlative RNA-chromatin maps toward the mechanistic dissection of how caRNAs organize regulatory hubs, modulate enhancer-promoter communication, and shape long-range genome interactions in the eye. As the catalog of pathogenic noncoding variants grows, the ability to decode and engineer caRNA networks will be central to future precision therapeutic strategies for ocular disorders.},
}

Humans
*Chromatin/genetics/metabolism
Animals
*Eye Diseases/genetics/metabolism/pathology
*RNA, Untranslated/genetics
Gene Expression Regulation
*Eye/metabolism/pathology/physiopathology
CRISPR-Cas Systems
Epigenesis, Genetic
Retinal Pigment Epithelium/metabolism

@article {pmid42900294,
year = {2026},
author = {Chen, X and Zhang, YS and Yan, D and Doan, T and Shen, LL and Taha, AT and Yang, D and Psaras, C and Callander, JK and Xin, NY and Shivkumar, A and Fawzi, AA and Yiu, G and Telander, DG and Leung, LB and Flaxel, C and Newman, JC and Keenan, JD and Stewart, JM},
title = {An exploratory study of the effect of metformin on the whole blood transcriptome of nondiabetic older adults with age-related macular degeneration.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42900294},
issn = {2509-2723},
support = {Unrestricted Grant//Research to Prevent Blindness/ ; Core Grant for Vision Research P30 EY037668/EY/NEI NIH HHS/United States ; },
abstract = {Metformin has received increasing attention for benefits beyond blood glucose lowering. The purpose of this study was to identify changes in whole blood transcriptome from a course of metformin in a randomized trial (NCT02684578) of nondiabetic older adults with age-related macular degeneration (AMD). We included patients who were ≥ 55 years of age, nondiabetic, and had geographic atrophy due to AMD. We excluded patients with metformin use for another reason, reduced renal or liver function, or other vitreoretinal diseases. Participants were randomized to metformin or control. The metformin group was prescribed 1000 mg metformin twice daily for 18 months. All eligible patients were approached for consent to blood sample collection. We performed metagenomic sequencing on whole blood samples and conducted differential expression analysis. Fifteen patients underwent blood collection, with eight in the metformin group and seven in the control group. No individual gene achieved statistical significance of difference between groups after correction for multiple comparisons. As a secondary, hypothesis-generating analysis, canonical pathway analysis found downregulation of interferon α/β signaling (P = 0.003, z score = -2.4), cell junction organization (P = 0.03, z score = -2.2), and epithelial mesenchymal transition pathways in the metformin group (P = 0.02, z score = -2.2). There was possible inhibition of upstream proinflammatory molecules and activation of anti-inflammatory molecules by metformin. In this small sub-study of a randomized trial, no gene was significantly changed after metformin exposure. Pathway enrichment analysis identified signals potentially consistent with metformin-associated modulation of "inflammaging" and other biological pathways which require validation in larger cohorts.},
}

@article {pmid42900412,
year = {2026},
author = {Kominami, T and Ueno, S and Ota, J and Sajiki, AF and Kimura, Y and Nishiguchi, KM},
title = {Clinical characteristics and long-term follow-up of extensive macular atrophy with pseudodrusen-like appearance in Japanese patients.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42900412},
issn = {1435-702X},
support = {23K15929//Japan Society for the Promotion of Science/ ; 23H03059//Japan Society for the Promotion of Science/ ; 25gm1510006s0105//Japan Agency for Medical Research and Development/ ; 23ym0126071h0002//Japan Agency for Medical Research and Development/ ; },
abstract = {PURPOSE: To describe the clinical characteristics and long-term follow-up findings of extensive macular atrophy with pseudodrusen-like appearance (EMAP) in a Japanese cohort.

METHODS: This retrospective observational study analyzed Japanese patients diagnosed with EMAP who underwent genetic tests, which did not detect known pathogenic variants of inherited retinal dystrophies or age-related macular degeneration. Patients underwent comprehensive ophthalmic evaluations, including multimodal imaging (fundus autofluorescence and optical coherence tomography) and full-field electroretinography.

RESULTS: This study included eight Japanese patients with EMAP, encompassing five males and three females. The mean follow-up period was 102.5 (range, 25-180) months. The mean best-corrected visual acuity declined from 0.18 to 1.08 logarithm of the minimum angle of resolution (right eye) over the follow-up period. Macular atrophy and peripheral paving-stone-like degeneration were present in 75% and 87.5% of patients, respectively. Rod responses were reduced in 62.5% of patients, and delayed flicker full-field electroretinography implicit times were observed in 62.5%. Longitudinal imaging suggested phenotypic changes in a limited number of cases including progression from a predominantly central pattern to confluent involvement in one patient.

CONCLUSION: Japanese patients with EMAP exhibited structural and functional abnormalities during long-term follow-up that were consistent with broader retinal involvement extending beyond the macula.},
}

@article {pmid42901982,
year = {2026},
author = {Sivaprasad, S and Stewart, MW and Wykoff, CC and Eichenbaum, D and Korobelnik, JF and Lanzetta, P and Chaudhary, V and Cheung, CMG and Gale, R and Munk, MR and Sakamoto, T and Stahl, A and Zarranz-Ventura, J and Wong, TY and Holz, FG and Loewenstein, A},
title = {Correction: Aflibercept 8 mg in neovascular age-related macular degeneration and diabetic macular oedema: Translating clinical trials into clinical practice.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41433-026-04887-2},
pmid = {42901982},
issn = {1476-5454},
}

@article {pmid42902106,
year = {2026},
author = {Sandau, N and Gorman, BR and Luo, J and Peachey, NS and Nordestgaard, BG and Tybjaerg-Hansen, A and Thomassen, JQ and Iyengar, SK and Frikke-Schmidt, R},
title = {Leukocytes and age-related macular degeneration.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {42902106},
issn = {1573-7284},
support = {National Institutes of Health/National Eye Institute//National Institutes of Health/National Eye Institute/ ; U.S. Department of Veterans Affairs//U.S. Department of Veterans Affairs/ ; U.S. Department of Veterans Affairs//U.S. Department of Veterans Affairs/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss. Leukocyte subtypes have been implicated in the pathogenesis, but causality remains uncertain. We investigated whether leukocyte counts are causally associated with clinically diagnosed AMD using observational and genetic analyses in three prospective cohorts. We included 117,714 individuals from the Copenhagen General Population Study (CGPS), 388,758 from the UK Biobank (UKB), and 285,612 from the Million Veteran Program (MVP), all of European ancestry and without clinically diagnosed AMD at baseline. In total, 27,130 incident AMD cases were identified. Baseline leukocyte counts were log2-transformed and standardized. Observational associations with incident AMD were estimated using Cox regression in CGPS and UKB, and then meta-analysed. Genetic instruments derived from genome-wide association studies were used for one-sample mendelian randomization (MR) and multivariable MR (MVMR) analyses in UKB and MVP, and estimates then meta-analysed. Observationally, a 1-standard deviation (SD) increase in leukocyte (Hazard ratio (HR) [95% confidence interval (CI)], 1.07 [1.05-1.09]), neutrophil (1.07 [1.05-1.09]), monocyte (1.05 [1.03-1.07]), basophil (1.06 [1.04-1.08]), and eosinophil (1.05 [1.03-1.06]) counts was associated with increased risk of clinically diagnosed AMD (all p < 0.0001). In the genetic analyses, a 1-SD increase in genetically determined eosinophil counts was causally associated with increased risk of clinically diagnosed AMD in the MR (OR [95% CI], 1.07 [1.00-1.15]; p = 0.038) and MVMR (OR [95% CI], 1.12 [1.03-1.21]; p = 0.006) analyses. This large-scale study provides observational and genetic evidence that elevated eosinophil counts are causally linked to risk of clinically diagnosed AMD. These findings highlight systemic eosinophil-driven immune pathways as potential contributors to AMD pathogenesis.},
}

@article {pmid42904881,
year = {2026},
author = {Ford, LM and Sun, K and Occelli, LM and Enfield, ME and Daruwalla, A and Boyd, RF and Kiser, PD and Petersen-Jones, SM},
title = {AAV Gene Augmentation Therapy Rescues the Phenotype in the RDH5-/- Cat Model of Fundus Albipunctatus.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {12},
pages = {45},
doi = {10.1167/iovs.67.12.45},
pmid = {42904881},
issn = {1552-5783},
mesh = {Animals ; *Genetic Therapy/methods ; *Dependovirus/genetics ; *Alcohol Oxidoreductases/genetics ; Cats ; Electroretinography ; Disease Models, Animal ; Genetic Vectors ; Gene Therapy Agents ; Phenotype ; Tomography, Optical Coherence ; Retinal Pigment Epithelium/metabolism/pathology ; *Eye Diseases, Hereditary/therapy/genetics/physiopathology ; *Night Blindness/therapy/genetics/physiopathology ; Immunohistochemistry ; Chromatography, High Pressure Liquid ; Retinal Diseases ; },
abstract = {PURPOSE: Retinol dehydrogenase 5 (RDH5) catalyzes the final oxidation for visual pigment regeneration of 11-cis-retinal as part of the visual cycle in the retinal pigment epithelium (RPE). In humans, RDH5 mutations cause fundus albipunctatus characterized by night blindness, accumulation of white-yellowish fundus spots, and, in a subset of patients, macular degeneration. Currently, there is an unmet need for therapies for patients with RDH5 mutations. Using a large-animal cat model of RDH5-associated disease (RDH5-/-), this study aimed to meet these needs through development of a gene augmentation therapy able to rescue RDH5-associated retinopathies.

METHODS: An adeno-associated virus serotype 2 with triple capsid mutations vector packaged with feline RDH5 cDNA (AAV-VMD2-fRDH5) was subretinally injected into 12 RDH5-/- cats. To assess expression and the impact of treatment on retinal function and structure, immunohistochemistry, high-performance liquid chromatography, rod and cone electroretinograms, spectral-domain optical coherence tomography, and semi-thin resin-embedded sectioning were performed.

RESULTS: The expression of the RDH5 transgene improved rod and cone photoreceptor functional recovery following light exposure and shows promise in slowing/halting area centralis (analogous to the human macula) degeneration.

CONCLUSIONS: This gene augmentation therapy is a promising approach for the treatment of RDH5-associated retinopathies.},
}

Animals
*Genetic Therapy/methods
*Dependovirus/genetics
*Alcohol Oxidoreductases/genetics
Cats
Electroretinography
Disease Models, Animal
Genetic Vectors
Gene Therapy Agents
Phenotype
Tomography, Optical Coherence
Retinal Pigment Epithelium/metabolism/pathology
*Eye Diseases, Hereditary/therapy/genetics/physiopathology
*Night Blindness/therapy/genetics/physiopathology
Immunohistochemistry
Chromatography, High Pressure Liquid
Retinal Diseases

@article {pmid42905386,
year = {2026},
author = {Adelman, J and Barker, R and Best, B and Fisher, R and Mason, M and Udaondo, P and Garhöfer, G and Csaky, K},
title = {Patient and Physician Perspectives on Oral Treatment in Ophthalmology.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42905386},
issn = {2193-8245},
abstract = {Antivascular endothelial growth factor (anti-VEGF) intravitreal (IVT) therapy injections are routinely used to treat retinal diseases, including diabetic macular edema (DME), proliferative diabetic retinopathy (PDR), and neovascular age-related macular degeneration (AMD [nAMD]). Despite their robust efficacy, IVTs may not be effective for all patients and can impact patient quality of life due to the need for frequent injections, ocular adverse events (AEs), and challenges around the injection itself. Oral therapy enabling fewer injections may have a beneficial impact on patients' lives. Several are currently in development for retinal diseases, and existing data suggest that patients would prefer oral to injectable therapies. However, challenges around this possible paradigm shift include potential systemic AEs, adherence and polypharmacy issues, and difficulties specifically targeting the eye with oral therapy. Additionally, it is unclear which healthcare professionals (HCPs) will be prescribers and how healthcare systems will adapt to provide oral therapy to patients. As oral treatment would be a new therapeutic modality for retinal disease, patient perspective studies on its use in this setting are limited. This commentary provides the perspectives of patient authors living with retinal diseases and those of expert clinicians involved in retinal disease management. We explore the potential future role for oral therapy in retinal disease alongside IVT, including possible barriers to uptake, a review of relevant existing literature, and lessons from oncology where a paradigm shift from parenteral to oral therapy has already happened. While challenges will arise for the introduction of new oral therapies, the benefits may be considerable, and some potential barriers may be less significant than the literature suggests. We hope this article will inform and educate patients and physicians about potential benefits and challenges for oral therapy in retinal disease and facilitate discussion around how best to support patients with the introduction of these novel therapies.Video abstract available for this article.},
}

@article {pmid42894102,
year = {2026},
author = {Chen, T and Xiang, Z and Zhang, Z and Sun, B and Ding, X and Wang, L and Yao, Y and Wu, Z and Liu, S and Lei, Y and Zhou, X and Zhao, J},
title = {Systemic Loss of Chromosome Y Associates With Age-Related Ophthalmic Diseases in Middle-Aged Men: A Longitudinal Multi-Omic Study.},
journal = {Aging cell},
volume = {25},
number = {10},
pages = {e70775},
pmid = {42894102},
issn = {1474-9726},
support = {2024YFC2510805//National Key Research and Development Program of China/ ; 23QA1401000//Shanghai Rising-Star Program/ ; QNKJ2024055//Shanghai Oriental Talent Plan Youth Program/ ; SHDC12025144//Shanghai Hospital Development Center Foundation/ ; },
mesh = {Humans ; Male ; *Chromosomes, Human, Y/genetics ; Multiomics ; Longitudinal Studies ; Middle Aged ; *Eye Diseases/genetics ; *Aging/genetics ; *Macular Degeneration/genetics ; },
abstract = {Maintaining health during global population aging represents a critical challenge, where mosaic loss of chromosome Y (LOY) in the hematopoietic system surfaces as a prevalent somatic mutation in aging men. However, its longitudinal impact on sensory organ degeneration remains insufficiently characterized. Analyzing 223,051 male participants from the UK Biobank, we demonstrated that LOY uniquely and independently predicted an increased risk of incident age-related macular degeneration (AMD) (Hazard Ratio = 0.611, 95% Confidence Interval: 0.397-0.942). Restricted cubic splines identified a critical risk escalation threshold at -0.17 for median log R ratio. Over a 15-year preclinical window, Olink plasma proteomics identified 41 prioritized proteins demonstrating divergent nonlinear kinetic profiles leading up to clinical diagnosis; notably, the elastin-degrading matrix metalloproteinase-12 deviated significantly 12 years prior to endpoint. Integrating single-cell RNA sequencing datasets of peripheral blood and choroidal tissues validated that CD16[+] circulatory monocytes and resident macrophages exhibited peak LOY frequencies. Furthermore, Y-deficient myeloid cells manifested a pro-inflammatory phenotype with cell-type-specific upregulation of IFI30 and CKB, bridging single-cell transcriptional activation with systemic proteomic dysregulation. Causal mediation analysis confirmed that peripheral monocyte counts significantly mediated the LOY-associated degenerative risk. Utilizing these prioritized proteomic signatures, a LightGBM machine learning framework achieved robust predictive performance for 5-year incident risk (AUC = 0.734). Collectively, these findings establish a distinct somatic mutation-immune-retinal axis, positioning systemic clonal mosaicism not merely as a marker of biological senescence but as an upstream driver of site-specific organ degeneration, offering novel strategies for early risk stratification and precision intervention in aging-related diseases.},
}

Humans
Male
*Chromosomes, Human, Y/genetics
Multiomics
Longitudinal Studies
Middle Aged
*Eye Diseases/genetics
*Aging/genetics
*Macular Degeneration/genetics

@article {pmid42894708,
year = {2026},
author = {Roa, C and Beuse, A and Schweig, A and Müller, S and Berger, K and Brandl, C and Brinker, T and Elbrecht, A and Finger, R and Geerling, G and Greiser, KH and Grohmann, C and Günther, K and Heid, I and Karch, A and Keil, T and Krepel, J and Leitzmann, M and Meinke-Franze, C and Peters, A and Schipf, S and Schulze, M and Schuster, AK and Willich, SN and Leitritz, MA and Ueffing, M and Berens, P},
title = {The German National Cohort: Ophthalmic Assessment, Baseline Profile, and Potential for Artificial Intelligence-Based Eye Research.},
journal = {Ophthalmology science},
volume = {6},
number = {11},
pages = {101408},
pmid = {42894708},
issn = {2666-9145},
abstract = {OBJECTIVE: To describe the ophthalmic examination protocol within the German National Cohort (NAKO)/NAKO Gesundheitsstudie, to report the baseline profile of participants undergoing ophthalmic assessment, and to illustrate the potential as a population-based resource for artificial intelligence (AI) research in eye health.

DESIGN: Baseline analysis of ophthalmic data within the nationwide, population-based multicenter prospective NAKO study.

PARTICIPANTS: Forty-eight thousand four hundred and sixty adults in the ophthalmic level 2 module of 205 053 adults enrolled in NAKO, aged 19-74 years, with a mean age 48.9 ± 12.5 years, and 52.7% were male.

METHODS: All participants underwent standardized biomedical examinations and detailed questionnaire-based data collection, including nondilated color fundus imaging, visual acuity testing, and a brief ocular history. Ocular health was summarized using descriptive statistics. Fundus image quality and morphological features (e.g., cup-to-disc ratio and arteriolar-to-venular ratio) were assessed using open-source deep learning models. Standard deep learning architectures were trained on the fundus images to predict age, sex, and blood pressure.

MAIN OUTCOME MEASURES: Percentage of fundus images graded as good quality; mean absolute error (MAE) for age and blood pressure prediction; accuracy for sex prediction.

RESULTS: The analysis includes 48 460 participants who completed the ophthalmic baseline examination of NAKO. Mean visual acuity (logarithm of the minimum angle of resolution) was 0.01 ± 0.20 (left eye, mean ± standard deviation) and 0.03 ± 0.21 (right eye). Self-reported ocular disease prevalence was 4.2% for cataract, 2.0% for glaucoma, and 0.9% for macular degeneration; 68.2% of fundus images were classified as gradable using 4 deep learning-based quality grading models. Morphological features showed systematic differences across age groups. Standard deep learning architectures showed comparative performance to the state-of-the-art for age, sex, and blood pressure prediction (2.96 MAE for age prediction, 0.84 accuracy for sex prediction, and 10.78 and 6.97 MAE for systolic and diastolic blood pressure prediction).

CONCLUSIONS: The German National Cohort provides a large-scale, nationwide population-based resource with visual acuity measurements and systemic health indicators, as well as color fundus images in about 50 000 NAKO participants. These data lay the groundwork for studying eye health in the general adult population in Germany and can serve as a strong foundation for developing and validating AI tools in eye health research.

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

@article {pmid42896642,
year = {2026},
author = {Al-Burak, SA and Sarraf, D and Naveed, F and Ali, M and Voznyy, V and Elganga, M and Sachdeva, K and Ahmed, F and Mihalache, A and Wong, D and Kertes, PJ and Muni, RH and Sadda, SR and Forte, P and Feo, A and Popovic, MM},
title = {Risk Factors for Retinal Pigment Epithelium Tears in Patients with Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.10.007},
pmid = {42896642},
issn = {1879-1891},
abstract = {TOPIC: To identify and synthesize clinical, imaging, and treatment-related risk factors associated with retinal pigment epithelium (RPE) tears in neovascular age-related macular degeneration (nAMD).

CLINICAL RELEVANCE: RPE tears are a vision-threatening complication of nAMD, occurring most often in eyes with pigment epithelial detachments (PEDs) and frequently temporally associated with initiation of anti-vascular endothelial growth factor (anti-VEGF) therapy. Improved recognition of high-risk PED features may enhance counseling and risk stratification.

METHODS: This systematic review and meta-analysis followed PRISMA guidelines and was prospectively registered in PROSPERO (CRD420251075278). MEDLINE, Embase, and CENTRAL were searched from inception to December 15, 2025. Randomized and non-randomized studies of adults (≥50 years) with nAMD evaluating candidate predictors of RPE tear were included. Two reviewers independently screened, extracted data, and assessed risk of bias (RoB 2, ROBINS-I). Random-effects meta-analyses were performed for baseline PED height and area, with per-study weighting, standardized mean difference (SMD), and leave-one-out sensitivity analyses. Certainty was assessed using GRADE.

RESULTS: Sixteen studies comprising 4,043 eyes were included. Five studies (55 tear eyes; 370 controls; 425 eyes) showed greater baseline PED height in eyes developing tears (mean difference [MD], 212.39 µm; 95% confidence interval [CI], 133.87-290.91; I² = 24.6%; SMD, 1.09). Four studies (48 tear eyes; 1,312 controls; 1,360 eyes) showed larger baseline PED area (MD, 5.80 mm²; 95% CI, 3.48-8.12; I² = 2.7%; SMD, 0.88). Both persisted across all leave-one-out iterations; omitting the study contributing 43.5% of the area weight increased the effect (MD, 7.11 mm²). Fibrovascular PED, greater basal diameter and volume, subretinal fluid, sub-RPE clefts, radial hyperreflective lines, and occult or hemorrhagic macular neovascularization were also associated with tears. Anti-VEGF agent selection was not consistently associated. Most studies were at moderate to serious risk of bias; certainty was very low.

CONCLUSION: Baseline PED morphology, particularly increased height, is the most consistently reported association with RPE tear in nAMD. Because the evidence is predominantly retrospective, largely unadjusted, and of very low certainty, these are associations rather than validated predictive markers. Prospective studies using standardized imaging protocols are needed.},
}

@article {pmid42898286,
year = {2026},
author = {Salleh, MN and Mulyadi Lai, HIA and Zain, MA and Ramachandran, V},
title = {Nano formulations of quercetin for ocular delivery.},
journal = {BioImpacts : BI},
volume = {16},
number = {},
pages = {33406},
pmid = {42898286},
issn = {2228-5652},
abstract = {Quercetin (QUE), a bioactive flavonoid with potent antioxidant, anti‑inflammatory, and neuroprotective properties, has emerged as a promising therapeutic candidate for age‑related macular degeneration, diabetic retinopathy, cataracts, glaucoma, dry eye disease, and allergic conjunctivitis. Its therapeutic effects are primarily mediated through modulation of key molecular pathways, including direct scavenging of reactive oxygen species (ROS), activation of Nrf2‑dependent antioxidant responses, inhibition of NF‑κB and MAPK signaling, and downregulation of pro‑inflammatory cytokines and angiogenic mediators such as VEGF. However, effective ocular delivery of QUE remains challenging because anatomical and physiological barriers severely limit drug penetration and retention, and because QUE itself exhibits poor aqueous solubility, chemical instability, rapid clearance, and a narrow therapeutic window at the tissue level. Recent advances in nanotechnology‑based delivery systems including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, micelles, and polymeric nanoparticles have shown considerable potential to enhance corneal and scleral permeability, prolong ocular residence time, improve QUE stability and bioavailability, and enable more controlled local exposure. This review critically evaluates recent progress in QUE‑loaded nanocarriers for ocular drug delivery, integrating mechanistic insights, formulation strategies, and preclinical and emerging clinical data, and discusses key challenges and opportunities for the safe and effective clinical translation of quercetin‑based ocular nanotherapeutics.},
}

@article {pmid42898393,
year = {2026},
author = {Li, Z and Yan, K and Rong, N and Sun, S and Liu, X and Xiu, Y and Zheng, Q and Sun, Y and Wu, J},
title = {Application of nanozyme-based drug delivery systems in the treatment of ROS-related ophthalmic diseases.},
journal = {International journal of pharmaceutics: X},
volume = {12},
number = {},
pages = {100680},
pmid = {42898393},
issn = {2590-1567},
abstract = {ROS-related ophthalmic diseases span the ocular surface as well as the anterior and posterior segments of the eye. Dry eye disease (DED), glaucoma, diabetic retinopathy (DR) and age-related macular degeneration (AMD) have distinct anatomical targets but share common pathophysiological features, including oxidative stress, inflammation, vascular dysfunction, epithelial injury or neurodegeneration. Conventional ocular drug delivery and therapeutic modalities are hindered by severe limitations, including low bioavailability in the posterior segment of the eye and the requirement for frequent invasive administration. Nanozymes, an emerging class of therapeutic agents that integrate the properties of nanomaterials with natural enzyme-like catalytic activity, can efficiently scavenge excess reactive oxygen species (ROS) in focal lesions, modulate inflammatory factors, and remodel the pathological microenvironment, thereby providing a novel approach to the treatment of ROS-related ophthalmic diseases. This review systematically elucidates the core characteristics and therapeutic mechanisms of four major categories of nanozymes, namely metal-based, metal oxide-based, carbon-based, and composite nanozymes. To overcome physiological barriers in ocular drug delivery, such as the cornea and the blood-retinal barrier (BRB), we discuss active targeted delivery strategies based on mucin-binding retention, biomimetic cell membrane coating, and molecular ligand-mediated targeting. Furthermore, we summarize the development of intelligent and controlled-release systems in response to specific pathological microenvironments, such as ROS, pH values, and others. Additionally, this review details the latest cutting-edge applications and therapeutic efficacies of nanozymes in specific ophthalmic diseases, including AMD, DR, dry eye disease, and glaucoma. Finally, we highlight the challenges of long-term biosafety evaluation in the bench-to-bedside clinical translation of nanozymes and provide perspectives on future research directions for developing multi-stimuli-responsive synergistic nanodelivery systems.},
}

@article {pmid42898608,
year = {2026},
author = {Kim, SB and Jeong, H and Kaelber, DC and Singh, RP and Talcott, KE},
title = {Examination of Alzheimer Disease and Antidementia Medications' Effect on Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261490775},
pmid = {42898608},
issn = {2474-1272},
abstract = {PURPOSE: To clarify the prevalence of age-related macular degeneration (AMD) in Alzheimer disease and assess whether antidementia medications modify this relationship.

METHODS: A retrospective cohort study was performed using electronic health record data (TriNetX) of adults aged 65 years and older with 10 or more years of ophthalmology follow-up. Patients with Alzheimer disease were compared with controls to estimate unadjusted and propensity score-adjusted prevalence odds ratios (ORs) for any AMD and progression to advanced AMD. Within the Alzheimer disease cohort, associations between duration of exposure to antidementia medication and AMD were evaluated.

RESULTS: AMD prevalence was higher in patients with Alzheimer disease (n = 4257) compared with controls (n = 140 378) before (prevalence OR, 1.57; 95% CI, 1.46-1.69), but not after adjustment (adjusted prevalence OR, 1.03; 95% CI, 0.92-1.15). Advanced AMD prevalence was comparable between cohorts, and no association was found between exposure to antidementia medication and AMD risk.

CONCLUSIONS: fter adjustment for confounders, Alzheimer disease and antidementia medications were not associated with AMD development or progression.},
}

@article {pmid42891122,
year = {2026},
author = {Cheung, CMG and Jiang, Z and Gilead, N and Kikushima, W and Curcio, CA and Teo, KYC},
title = {Age-Related Hypofluorescent Indocyanine Green Angiography Spots: Prevalence, Characteristics, and Associated Features in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {11},
pages = {101400},
pmid = {42891122},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the frequency and associated features of detecting age-related scattered hypofluorescent spots (ASHS) on indocyanine green angiography (ICGA) among fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD).

DESIGN: Imaging analysis.

PARTICIPANTS: Prospectively recruited cohort with treatment-naive nAMD.

METHODS: Patients underwent protocolized examination. Indocyanine green angiography was used to evaluate the presence of ASHS. Choriocapillaris vessel density was determined using OCT angiography (OCTA). The development of incident exudative age-related macular degeneration over 12 months was recorded.

MAIN OUTCOME MEASURES: Prevalence and associated features of ASHS.

RESULTS: We included 142 patients. Macular neovascularization (MNV)-subtype in the fellow eye was polypoidal choroidal vasculopathy (PCV; 60.5%), type I/mixed MNV (26.1%), type II (9.9%), and type III (3.5%). According to ICGA, eyes were categorized into homogeneous (n = 48, 33.8%), ASHS (n = 46, 32.3%), and drusen/reticular pseudodrusen (RPD) groups (n = 48, 33.8%). The ASHS group was significantly younger than the drusen/RPD group (68.4 vs. 75.5 years; P < 0.001). The ASHS group had shorter axial length (23.52 vs. 24.32; P = 0.047) than the homogeneous group and had better vision (0.17 vs. 0.29; P = 0.012) and greater subfoveal choroidal thickness (262.28 vs. 183.04 μm; P = 0.006) than the drusen/RPD group. Choriocapillaris vessel density was similar between the ASHS group and the homogeneous group (71.1% vs. 71.2%; P = 0.934), but lower in the drusen/RPD group (64.6%; P = 0.002). Fellow eye MNV-subtype was predominantly PCV in the ASHS and homogeneous groups (78.26% and 75.00%; P = 0.78) but lower in the drusen/RPD group (29.2%; P < 0.001). The ASHS group had lower total cholesterol than the homogeneous group (4.31 vs. 4.56mmol/L; P = 0.039) and the drusen/RPD group (4.84 mmol/L; P = 0.028).

CONCLUSIONS: One in 3 fellow eyes of patients with unilateral nAMD in this Asian population exhibited ASHS lesions. Choriocapillaris vessel density based on OCTA was similar between the ASHS and the homogeneous groups, supporting the hypothesis for reduced transit of indocyanine green-laden lipoproteins across the Bruch membrane.

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

@article {pmid42891766,
year = {2026},
author = {Mehany, SN and Vécsei-Marlovits, PV and Boltz, A},
title = {A retrospective analysis of treatment switch from faricimab to aflibercept 8 mg in nAMD.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42891766},
issn = {1573-2630},
mesh = {Humans ; *Recombinant Fusion Proteins/administration & dosage ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage/antagonists & inhibitors ; Retrospective Studies ; Intravitreal Injections ; *Visual Acuity ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration & dosage ; Female ; Male ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis ; Treatment Outcome ; *Drug Substitution ; Follow-Up Studies ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Antibodies, Bispecific ; },
abstract = {PURPOSE: Macular neovascularization is one of the most common causes of irreversible vision loss. Intravitreal injections with anti-vascular endothelial growth factor are the treatment of choice. In recent years, new drugs such as faricimab and aflibercept 8 mg have paved the way for longer intervals between intravitreal injections. However, there are currently very few comparative studies on these longer-acting drugs.

METHODS: This retrospective analysis included patients with at least three consecutive intravitreal injections of faricimab due to neovascular age-related macular degeneration who were subsequently switched from faricimab to aflibercept 8 mg in 2024. The primary outcome was the change in central retinal thickness as measured by optical coherence tomography. The secondary outcome was best-corrected visual acuity.

RESULTS: 41 eyes of 38 patients were included. There were no statistically significant changes in retinal thickness. Best-corrected visual acuity showed a trend towards deterioration, however not statistically significant. One patient experienced a tear of the retinal pigment epithelium after receiving the first injection of aflibercept 8 mg.

CONCLUSION: This retrospective analysis did not show statistically significant changes in central retinal thickness or best-corrected visual acuity after treatment switch from faricimab to aflibercept 8 mg.},
}

Humans
*Recombinant Fusion Proteins/administration & dosage
*Receptors, Vascular Endothelial Growth Factor/administration & dosage/antagonists & inhibitors
Retrospective Studies
Intravitreal Injections
*Visual Acuity
Tomography, Optical Coherence/methods
Angiogenesis Inhibitors/administration & dosage
Female
Male
Aged
*Wet Macular Degeneration/drug therapy/diagnosis
Treatment Outcome
*Drug Substitution
Follow-Up Studies
Aged, 80 and over
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Antibodies, Bispecific

@article {pmid42885636,
year = {2026},
author = {Fursova, AZ and Vasilyeva, MA and Derbeneva, AS and Amir, IM and Tarasov, MS and Nikulich, IF and Karlash, YA and Agamian, ER},
title = {[Subretinal fibrosis in neovascular age-related macular degeneration: risk factors, mechanisms of development, and current options for prevention and treatment].},
journal = {Vestnik oftalmologii},
volume = {142},
number = {5},
pages = {122-132},
doi = {10.17116/oftalma2026142051122},
pmid = {42885636},
issn = {0042-465X},
mesh = {Humans ; Fibrosis/prevention & control ; *Angiogenesis Inhibitors/pharmacology ; Risk Factors ; *Macular Degeneration/complications/drug therapy ; *Retina/pathology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Angiopoietin-2/metabolism ; },
abstract = {The results of numerous randomized clinical trials and clinical practice have demonstrated the effect of angiogenesis inhibitors (anti-VEGF agents) on the activity and growth of the neovascular complex in neovascular age-related macular degeneration (nAMD). At the same time, a reduction in the risk of macular fibrosis has been demonstrated, with its incidence decreasing from 39-100% in the "pre-antiangiogenic era" to 20.4-61.4% during anti-VEGF therapy. The main factors determining the risk of subretinal fibrosis are disease activity, timing of treatment initiation, treatment regimen and regularity, and type of drug. Fluctuations in retinal thickness and volatility of specific fluid compartments lead to an increase in the volume of subretinal hyperreflective material (SHRM) and hinder complete restoration of ellipsoid zone integrity. Extensive investigation of the role of angiopoietin-2 (Ang-2) in the development of fibrosis has shown that it acts not only as a cofactor of angiogenesis but also as an independent regulator of fibrogenesis through vascular destabilization with increased VEGF-mediated permeability and exudation, activation of macrophages and microglia with production of TGF-β and CTGF, as well as cross-talk with classical fibrotic pathways. The synergistic action of Ang-2 and VEGF-A promotes subretinal scarring and underscores the high potential of bispecific therapy for improving clinical outcomes in patients with nAMD. Compensatory activation of Ang-2 during anti-VEGF monotherapy may sustain tissue remodeling, contributing to the development of treatment resistance. Preclinical studies in models of choroidal neovascularization and clinical data on the effectiveness of faricimab 6 mg through dual Ang-2/VEGF-A inhibition have demonstrated not only superiority in controlling exudation and resolving retinal edema, but also a targeted effect on preventing proliferation and the development of subretinal fibrosis, as evidenced by a significant reduction in SHRM volume - a key precursor of fibrotic changes.},
}

Humans
Fibrosis/prevention & control
*Angiogenesis Inhibitors/pharmacology
Risk Factors
*Macular Degeneration/complications/drug therapy
*Retina/pathology
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Angiopoietin-2/metabolism

@article {pmid42888551,
year = {2026},
author = {Hu, LW and Landers, MR and Chien, LC and Lee, SP and Wu, FL},
title = {Presence of lower limb joint arthritis moderates the interrelationship between vision impairment and fear of falling avoidance behavior in older adults: A cross-sectional study.},
journal = {Medicine},
volume = {105},
number = {42},
pages = {e51126},
doi = {10.1097/MD.0000000000051126},
pmid = {42888551},
issn = {1536-5964},
mesh = {Humans ; Male ; *Accidental Falls/prevention & control/statistics & numerical data ; Aged ; Female ; *Fear/psychology ; Cross-Sectional Studies ; *Arthritis/complications/psychology/physiopathology ; *Lower Extremity/physiopathology ; *Vision Disorders/psychology/complications ; Middle Aged ; Surveys and Questionnaires ; },
abstract = {Falling is a common concern for older adults. Previous studies showed that mobility performance is significantly lower in those with age-related eye diseases or lower limb arthritis, contributing to their increased fall risk. However, it is currently unknown how the co-presence of these 2 age-related sensorimotor impairments interacts to affect fear of falling (FOF) and associated activity-avoidance behaviors. A total of 200 participants recruited from an outpatient regional medical center (127 women, 73 men, age = 65.5 ± 8.4 years) participated in this study. The presence of age-related, uncorrected eye diseases (i.e., cataracts, glaucoma, retinopathy, and macular degeneration) and arthritis in the lower limb joints were recorded. Geriatric Fear of Falling Measure, Fear of Falling Avoidance Behavior Questionnaire, and Timed Up-and-Go test were used to assess FOF, avoidance behavior, and physical mobility, respectively. Moderated mediation analyses, corrected for age and body mass index, were performed. With the Geriatric Fear of Falling Measure as mediator, lower limb arthritis significantly moderated the indirect effects of eye disease on Timed Up-and-Go test performance (B = 1.00; 95% confidence interval = 0.06-2.11) and the Fear of Falling Avoidance Behavior Questionnaire score (B = 5.68; 95% confidence interval = 0.36-11.11). Namely, participants with uncorrected age-related eye disease and lower limb arthritis exhibited significantly poorer mobility and greater avoidance behavior than those without arthritis. The presence of age-related eye diseases exacerbates FOF avoidance behavior and leads to diminished mobility in older adults. The severity of FOF is moderated by the presence of lower limb arthritis. These findings suggest that effective fall prevention strategies for older adults should incorporate comprehensive vision, musculoskeletal, and behavioral evaluations.},
}

Humans
Male
*Accidental Falls/prevention & control/statistics & numerical data
Aged
Female
*Fear/psychology
Cross-Sectional Studies
*Arthritis/complications/psychology/physiopathology
*Lower Extremity/physiopathology
*Vision Disorders/psychology/complications
Middle Aged
Surveys and Questionnaires

@article {pmid42888956,
year = {2026},
author = {Kjellström, U and Tornqvist, K and Baudin, K and Regardt, M and Schroeder, M},
title = {Epidemiology of visual impairment and rehabilitation measures in adults-Data from the Swedish Quality Registry for Rehabilitation in Visual Impairment.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70258},
pmid = {42888956},
issn = {1755-3768},
support = {//Stiftelsen för Synskadade i f.d. Malmöhus län/ ; //Armec Lindebergs stiftelse/ ; //Stiftelsen Kronprinsessan Margaretas Arbetsnämnd för Synskadade/ ; //Skåne County Council Research and Development Foundation/ ; },
abstract = {PURPOSE: To describe the Swedish Quality Registry for Rehabilitation in Visual Impairment (SKRS) and present rehabilitation measures and underlying diagnoses of visual impairment and blindness in adults in Sweden.

METHODS: The study includes data from the SKRS collected between January 2016 and December 2025 for patients aged ≥20 years who received rehabilitation services from low vision centres in Sweden. The degree and underlying causes of visual impairment, as well as rehabilitation interventions, were analysed.

RESULTS: In 2025, SKRS recorded 12 622 registrations for 11 810 unique patients, with women accounting for 62%. The median waiting time from referral to first visit was 37 days. Most patients had a moderate visual impairment. In 2025, age-related macular degeneration (AMD) represented the most common diagnosis (50.2%), followed by glaucoma (18.3%), blindness of unspecified cause/visual impairment (5.9%), retinal diseases (5%), diabetic retinopathy (2.8%) and optic nerve diseases (2.2%). The most frequently registered procedure codes were in the group of assistive technology with 30.3%, followed by investigative procedures with 26.1% and follow-up with 19.9%. The proportion of International Classification of Functioning, Disability and Health based instruments had increased significantly; from 0.04% in 2016 to 72.5% in 2025. The proportion of individual rehabilitation plans had risen by 18.6% since the start of the COVID-19 pandemic-from 53.2% in 2020 to 71.8% in 2025.

CONCLUSION: SKRS provides representative data on rehabilitation measures and associated diagnoses among adults with visual impairments in Sweden. The data confirm that AMD and glaucoma are the most common causes and highlight inequalities in access to visual rehabilitation.},
}

@article {pmid42889642,
year = {2026},
author = {Wenhua, Y and Wenjing, M and Yan, D and Fei, L and Juan, C and Xia, T and Yu, G and Xin, L and Yanlin, H and Ya, G and Xuelin, Y and Jing, L and Meimin, J and Wenyi, L and Yilin, K and Hongke, L and Yating, L},
title = {Should ApoE4 gene editing therapy be approached with caution when AD is accompanied by retinal neurodegenerative diseases?.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1934307},
pmid = {42889642},
issn = {1664-2295},
mesh = {Humans ; *Apolipoprotein E4/genetics ; *Gene Editing/methods ; *Alzheimer Disease/genetics/therapy/complications ; *Genetic Therapy/methods ; Animals ; *Neurodegenerative Diseases/genetics/therapy/complications ; *Retinal Diseases/genetics/therapy/complications ; Macular Degeneration/genetics/therapy ; },
abstract = {Apolipoprotein E4 (ApoE4) is the strongest genetic risk factor for Alzheimer's disease (AD), and ApoE4-directed gene editing and gene therapy have emerged as promising therapeutic strategies for AD, although they remain investigational and are not yet an established mainstream treatment. Interestingly, however, ApoE4 is reported to be associated with a reduced risk of retinal degenerative diseases such as glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). Therefore, should ApoE4 gene editing therapy be approached with caution when AD occurs concurrently with glaucoma, AMD, or DR? In view of these and based on the existing literature, the present study detailed the distinct roles of ApoE4 in AD, glaucoma, AMD, and DR, with a purpose to offer valuable insights into subsequent ApoE4 gene editing therapies. We also summarise the ApoE-targeted therapeutic programmes currently in preclinical and early clinical development, delineate the remaining translational challenges, and discuss how patients with coexisting retinal neurodegenerative disease might be evaluated and monitored.},
}

Humans
*Apolipoprotein E4/genetics
*Gene Editing/methods
*Alzheimer Disease/genetics/therapy/complications
*Genetic Therapy/methods
Animals
*Neurodegenerative Diseases/genetics/therapy/complications
*Retinal Diseases/genetics/therapy/complications
Macular Degeneration/genetics/therapy

@article {pmid42882470,
year = {2026},
author = {Ning, JY and Wang, B and Yamamoto, MI and Yamada, KH},
title = {Fibrotic Remodeling in Retinal Vascular Diseases: Cellular Origins, Molecular Mechanisms, and Therapeutic Perspectives.},
journal = {Cells},
volume = {15},
number = {19},
pages = {},
pmid = {42882470},
issn = {2073-4409},
support = {AHEAD-DBG-23-1156429-01-MM//American Cancer Society/ ; 1R01CA289701-01A1/NH/NIH HHS/United States ; },
mesh = {Humans ; Animals ; Fibrosis ; Diabetic Retinopathy/pathology ; *Retinal Diseases/pathology/therapy ; Macular Degeneration/pathology ; Signal Transduction ; },
abstract = {Fibrosis is a major vision-threatening complication of neovascular retinal diseases, including neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR). Although vascular endothelial growth factor (VEGF) inhibition effectively suppresses vascular leakage and neovascularization, some patients still develop fibrosis and experience irreversible vision loss. Recent studies have identified multiple interconnected signaling pathways that contribute to fibrotic progression, highlighting the potential need for combination or multitargeted therapeutic strategies. This review summarizes the cellular origins of myofibroblasts, the molecular mechanisms underlying fibrosis, and recent advances in antifibrotic therapies. We particularly highlight the angio-fibrotic switch, mesenchymal transition, cellular stress responses, extracellular matrix remodeling, mechanotransduction, and emerging therapeutic approaches for ocular fibrosis. Relevant preclinical and clinical studies were identified through searches of PubMed and clinical trial registries.},
}

Humans
Animals
Fibrosis
Diabetic Retinopathy/pathology
*Retinal Diseases/pathology/therapy
Macular Degeneration/pathology
Signal Transduction

@article {pmid42883974,
year = {2026},
author = {Tomita, H},
title = {Special Issue: Cell Signaling and Molecular Pathology of Retinal Diseases: 2nd Edition.},
journal = {International journal of molecular sciences},
volume = {27},
number = {19},
pages = {},
pmid = {42883974},
issn = {1422-0067},
mesh = {Humans ; *Signal Transduction ; *Retinal Diseases/metabolism/pathology ; Animals ; },
abstract = {Retinal degenerative diseases, a broad group encompassing age-related macular degeneration (AMD) and various forms of inherited retinal disease (IRD), are among the leading causes of irreversible blindness worldwide [...].},
}

Humans
*Signal Transduction
*Retinal Diseases/metabolism/pathology
Animals

@article {pmid42885622,
year = {2026},
author = {Andreeva, IV and Stoyukhina, AS and Smolin, SA and Viem, H},
title = {[Modern diagnostic possibilities for peripapillary neovascular membranes. Report 2. Differential diagnostic features].},
journal = {Vestnik oftalmologii},
volume = {142},
number = {5},
pages = {5-15},
doi = {10.17116/oftalma20261420515},
pmid = {42885622},
issn = {0042-465X},
mesh = {Humans ; Middle Aged ; Diagnosis, Differential ; Female ; Tomography, Optical Coherence/methods ; Male ; Adult ; Aged ; *Optic Disk/pathology/diagnostic imaging/blood supply ; Aged, 80 and over ; Fluorescein Angiography/methods ; *Hemangioma/diagnosis ; *Retinal Neovascularization/diagnosis/etiology ; *Optic Nerve Neoplasms/diagnosis/complications ; Young Adult ; },
abstract = {UNLABELLED: Hemangiomas of the optic nerve head (ONH) is a rare hamartoma that in some cases requires differential diagnosis with peripapillary subretinal neovascular membranes (SNMs).

OBJECTIVE: The study aimed to identify the clinical and tomographic differential diagnostic signs of ONH hemangiomas and juxtapapillary SNMs.

MATERIAL AND METHODS: The study included 61 patients aged 22-90 years: 14 eyes with ONH hemangiomas and 58 eyes with SNMs of various etiologies (neovascular age-related macular degeneration, angioid streaks, pachychoroid neovasculopathy, and chronic central serous chorioretinopathy). In addition to standard ophthalmic examination, all patients underwent optical coherence tomography (OCT) and OCT angiography (OCT-A) using the OCT-2 Spectralis system (Heidelberg Engineering, Germany).

RESULTS: ONH hemangiomas were detected in younger patients (46±17 years), whereas SNMs were found in older patients (65-76 years). Hemangiomas were located juxtapapillary, with no preferred side relative to the ONH, whereas SNMs were located predominantly temporal to the ONH and were often bilateral. Retinal thickness at the lesion site was significantly greater in hemangiomas (962±336 µm vs 424-563 µm in SNMs). Subfoveal choroidal thickness in hemangiomas corresponded to the age norm, whereas in SNMs it varied depending on the etiology. OCT showed that ONH hemangiomas were characterized by a "honeycomb-like" intraretinal structure, absence of edema over the lesion, and an intact Bruch's membrane; SNMs were characterized by intraretinal edema, pigment epithelial detachment, and accumulation of intraretinal and subretinal fluid. OCT-A showed that vessels in ONH hemangiomas were located in the superficial or deep retinal capillary plexus, whereas in SNMs they were located at the level of the avascular retinal layers.

CONCLUSION: ONH hemangiomas are unilateral lesions detected in young patients and primarily affecting the inner retinal layers with formation of a "honeycomb-like" structure. SNMs are more often a bilateral process involving the outer retinal layers and associated with age-related or pathologic choroidal changes. An important differential diagnostic feature is the level of localization of the pathologic vessels on OCT-A. Therefore, comprehensive diagnostics, including ophthalmoscopy, OCT, and OCT-A, are important for diagnosis and for choosing the correct treatment strategy.},
}

Humans
Middle Aged
Diagnosis, Differential
Female
Tomography, Optical Coherence/methods
Male
Adult
Aged
*Optic Disk/pathology/diagnostic imaging/blood supply
Aged, 80 and over
Fluorescein Angiography/methods
*Hemangioma/diagnosis
*Retinal Neovascularization/diagnosis/etiology
*Optic Nerve Neoplasms/diagnosis/complications
Young Adult

@article {pmid42882265,
year = {2026},
author = {Alutaibi, M and Alazmi, M},
title = {Comparative Evaluation of EfficientNet-B3, Vision Transformers, and RETFound for Seven-Category Retinopathy Fundus Image Classification.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {19},
pages = {},
doi = {10.3390/diagnostics16193109},
pmid = {42882265},
issn = {2075-4418},
abstract = {Background/Objectives: Retinal fundus photography is the most widely available means of screening for sight-threatening disease, but it is difficult to read: several conditions leave overlapping signs on the same photograph, the features that separate them are often subtle and confined to small regions of the retina, and a single image carries no systemic context, so an automated reader must resolve categories on which experienced clinicians themselves agree only moderately. Methods: We compared five deep learning architectures-EfficientNet-B3, DenseNet-121, ViT-Base/16, Inception-V3, and RETFound ViT-Large-for simultaneous seven-class retinal disease classification on a multi-source fundus image benchmark, in a retrospective computational study using stratified five-fold cross-validation. We pooled 11,223 patient-eye fundus images from three publicly available, de-identified datasets (ODIR-5K, RFMiD, and APTOS 2019) spanning age-related macular degeneration (AMD), cataract, diabetic retinopathy (DR), glaucoma, hypertensive retinopathy, pathological myopia, and normal fundus; the cohort was markedly class-imbalanced (DR, 62.5%; normal, 25.6%; each remaining class < 3%), and no new patient data were collected. Images were deduplicated by MD5 hash and split at the patient level to eliminate data leakage, with a fixed 15% held-out test set and five stratified cross-validation folds; training images received Ben Graham illumination normalization and class-balancing augmentation, while validation and test images were unaugmented. Three ImageNet-pretrained CNNs (EfficientNet-B3, DenseNet-121, Inception-V3), ViT-Base/16, and RETFound ViT-Large (pretrained on 1.6 million retinal photographs via masked autoencoding) were trained; the primary outcome was the five-fold mean weighted-averaged F1 score, pairwise comparisons used paired t-tests on fold-level F1 (df= 4), and Grad-CAM was applied for explainability. Results: EfficientNet-B3 achieved the highest five-fold mean accuracy (95.53%; weighted-F1, 0.9507) and significantly outperformed RETFound ViT-Large (ΔF1=+0.0255; t=9.70; p<0.001), ViT-Base/16 (ΔF1=+0.0075; t=9.20; p<0.001), and Inception-V3 (ΔF1=+0.0103; t=8.38; p<0.001), while performing comparably to DenseNet-121 (t=2.24; p=0.089); Grad-CAM showed clinically plausible activation localization for the CNN architectures. Conclusions: A compact, resource-efficient CNN thus matched or exceeded a substantially larger retinal foundation model and Vision Transformers, indicating that larger domain-specific foundation models are not inherently superior for heterogeneous retinal screening; because such compact models run on commodity hardware, they may offer more practical screening solutions for community, rural, and resource-limited settings where ophthalmologist coverage is scarcest. External validity across imaging sources and populations remains unproven, underscoring that prospective, multicenter validation must precede clinical deployment. A provenance audit of this pooled cohort subsequently found it confounded. The audit identified five failure modes, three of them decisive: image width alone reproduced the diabetic retinopathy label at 99.98% accuracy using no retinal pixels, source and label were almost perfectly dependent with a Cramér's V of 0.9996, and diabetic retinopathy recall was exactly 1.0000 for all five architectures. The cohort was rebuilt from a single source with per-eye labels, and nine architectures were retrained under one protocol with external validation. The corrected headline is a macro-AUC of 0.930 internally and 0.978 externally, with a macro-F1 of 0.686. No architecture is declared superior, and the pooled-cohort conclusion does not stand.},
}

@article {pmid42880817,
year = {2026},
author = {Madheswaran, G and S Ve, R and Ganeshrao, SB and Raman, R and Palaniswamy, HP},
title = {Exploring emotion identification and categorisation in simulated central vision loss: an event-related potential study.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {4},
pages = {},
doi = {10.1136/bmjophth-2025-002689},
pmid = {42880817},
issn = {2397-3269},
}

@article {pmid42881368,
year = {2026},
author = {Bilgeç, MD and Özaslan, MK and Taş, E and Erol, N},
title = {Type 4 macular neovascularization in a consecutive age-related macular degeneration cohort: detected prevalence and multimodal imaging findings.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42881368},
issn = {1471-2415},
mesh = {Humans ; Retrospective Studies ; Female ; Tomography, Optical Coherence/methods ; *Multimodal Imaging ; Male ; Fluorescein Angiography/methods ; Prevalence ; Aged ; Aged, 80 and over ; *Retinal Neovascularization/epidemiology/diagnostic imaging ; *Macular Degeneration ; Visual Acuity ; Fundus Oculi ; *Macula Lutea/pathology ; },
abstract = {BACKGROUND: To determine the detected prevalence of type 4 macular neovascularization (MNV) within a retrospectively screened age-related macular degeneration (AMD) cohort and to characterize its clinical, structural, and angiographic features.

METHODS: This single-center retrospective cohort study included 4658 structural OCT examinations from 962 eyes of 500 patients with age-related macular degeneration (AMD). Eyes with structural OCT findings suggestive of type 4 MNV underwent multimodal evaluation via structural OCT and available OCT angiography (OCTA). Cases were categorized as definite, probable, or non-type 4 MNV according to predefined multimodal imaging criteria. Detected prevalence within the screened cohort was calculated at the patient and eye levels with exact 95% Clopper-Pearson confidence intervals (CIs).

RESULTS: The detected prevalence of definite type 4 MNV within the entire consecutive AMD cohort was 2.00% (95% confidence interval [CI], 0.96-3.65%) at the patient level and 1.04% (95% CI, 0.50-1.90%) at the eye level. The hyperreflective oblique band (HOB), subretinal hyperreflective material (SHRM), and ellipsoid zone (EZ) loss were present in all the definite cases. Central posterior hyaloid fibrosis (CPHF) was observed in half of the definite cases, whereas the remaining eyes exhibited posterior hyaloid central hyperreflectivity (PHCH). By definition, the OCTA criterion of a continuous flow signal extending from the inner choroid to the preretinal space was fulfilled in all definite cases. During follow-up, HOB, CPHF, and PHCH remained stable, whereas exudative activity varied.

CONCLUSIONS: Within this consecutive AMD cohort, type 4 MNV was an uncommon phenotype characterized by recognizable structural and angiographic features. Structural OCT was used to identify eyes suspicious for type 4 MNV, whereas designation as definite type 4 MNV required demonstration on OCTA of the continuous flow signal specified in the predefined criteria. Our findings further characterize the clinical, structural, and angiographic features of type 4 MNV in this retrospective cohort.},
}

Humans
Retrospective Studies
Female
Tomography, Optical Coherence/methods
*Multimodal Imaging
Male
Fluorescein Angiography/methods
Prevalence
Aged
Aged, 80 and over
*Retinal Neovascularization/epidemiology/diagnostic imaging
*Macular Degeneration
Visual Acuity
Fundus Oculi
*Macula Lutea/pathology

@article {pmid42882062,
year = {2026},
author = {Seweryn, M and Rękas, M and Figurska, M},
title = {Effectiveness and Treatment Burden of Faricimab in Neovascular AMD: A Real-World Analysis of Treatment-Naïve and Previously Treated Patients in Poland.},
journal = {Journal of clinical medicine},
volume = {15},
number = {19},
pages = {},
doi = {10.3390/jcm15197602},
pmid = {42882062},
issn = {2077-0383},
abstract = {Background/Objectives: Faricimab is a bispecific antibody targeting vascular endothelial growth factor A and angiopoietin-2, developed to extend treatment intervals in neovascular age-related macular degeneration (nAMD). Real-world evidence on faricimab within the Polish national drug program remains scarce. This study aimed to assess one-year clinical and treatment outcomes of faricimab for nAMD using real-world data from the Polish Therapeutic Program Monitoring System (SMPT). Methods: In this retrospective, non-randomized registry study, 322 patient-eye records treated with faricimab within the national drug program between January 2024 and April 2025 were analysed. Eligibility required at least 360 days between the first and last injections. Eyes were stratified into treatment-naïve (n = 70) and continuation (switched from another anti-vascular endothelial growth factor (anti-VEGF) agent; n = 252). Results: Median baseline best-corrected visual acuity (BCVA) was 70 [60, 77] letters overall, with no significant difference between subgroups (p = 0.59). At one year, treatment-naïve eyes improved to 75 [66, 79] letters (Δ +5 [0, 10]), whereas continuation eyes were maintained (Δ 0 [-5, 5]; between-group p < 0.001). A clinically meaningful (≥10-letter) gain occurred in 16% of eyes overall, more often in treatment-naïve than continuation eyes (27% vs. 12%; p = 0.004). Central retinal thickness (CRT) decreased significantly in all subgroups, with a greater reduction in treatment-naïve eyes. Intraocular pressure (IOP) remained stable (median Δ 0 mmHg). Patients received a median of 8 [7, 8] injections; injection numbers fell from 5 [4, 5] in the first half-year to 3 [2, 3] in the second, and intervals extended from approximately four to eight weeks. Conclusions: Within the Polish program, one year of faricimab was associated with stable-to-improved vision, anatomical improvement, and progressive extension of injection intervals after the mandated loading phase. Given the observational, single-arm design and the persister-only cohort, findings represent associations rather than comparative effectiveness.},
}

@article {pmid42882132,
year = {2026},
author = {Kang, CG and Kim, SK and Kang, H and Park, SI},
title = {Interocular Differences in Visual Acuity and Refractive Status Between Unilateral Early and Late Age-Related Macular Degeneration: A Nationwide Population-Based Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {19},
pages = {},
doi = {10.3390/jcm15197672},
pmid = {42882132},
issn = {2077-0383},
abstract = {Background/Objectives: Age-related macular degeneration (AMD) may affect the two eyes asymmetrically, but visual impairment is commonly classified by visual acuity (VA) in the better-seeing eye. We compared interocular-presenting VA differences in unilateral early versus late AMD, assessed the association between late AMD and worse VA in the AMD-affected eye, and compared refractive status between the affected and fellow eyes. Methods: We analyzed 1112 adults aged ≥40 years with unilateral AMD (1049 early and 63 late) from the 2017-2020 Korea National Health and Nutrition Examination Survey. Interocular VA difference was calculated as the logMAR VA of the AMD-affected eye minus that of the fellow eye. Survey-weighted modified Poisson regression estimated prevalence ratios (PRs), adjusting for age, sex, anisometropia, and the interocular difference in absolute spherical equivalent refraction. Exploratory analyses examined neovascular AMD and geographic atrophy separately, and sensitivity analyses assessed alternative model specifications. Results: Mean interocular differences were -0.004 logMAR (95% confidence interval [CI], -0.016 to 0.008) in early AMD and 0.184 logMAR (95% CI, 0.077 to 0.291) in late AMD. The weighted proportions with VA ≥ 0.2 logMAR worse in the AMD-affected eye were 10.15% and 58.31%, respectively. The adjusted PR for this outcome was 4.95 (95% CI, 3.46-7.09; p < 0.001) for late versus early AMD. Exploratory subtype-specific analyses showed similar associations for neovascular AMD and geographic atrophy. No statistically significant interocular differences in refractive status or astigmatism severity were detected; however, the wide 95% CIs, particularly in the late AMD group, precluded conclusions of equivalence. Conclusions: Unilateral late AMD was associated with greater interocular presenting VA asymmetry than early AMD, and the association remained consistent across sensitivity analyses. However, these cross-sectional findings do not establish longitudinal progression or directly demonstrate implications for spectacle prescribing or binocular visual function.},
}

@article {pmid42875766,
year = {2026},
author = {Siekerman, MME and Kristiansen, IS and Jørstad, ØK and Bragadóttir, R and Burger, EA},
title = {Cost-effectiveness of the Port Delivery Platform compared with intravitreal injection of anti-vascular endothelial growth factor for patients with neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42875766},
issn = {1471-2415},
mesh = {Humans ; Intravitreal Injections/economics ; Cost-Benefit Analysis ; *Angiogenesis Inhibitors/administration & dosage/economics ; *Recombinant Fusion Proteins/administration & dosage/economics ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage ; Cost-Effectiveness Analysis ; *Ranibizumab/administration & dosage/economics ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Drug Delivery Systems/economics ; Female ; *Wet Macular Degeneration/drug therapy/economics ; Male ; Visual Acuity ; Aged ; Quality-Adjusted Life Years ; Aged, 80 and over ; },
abstract = {BACKGROUND: Standard ranibizumab anti-vascular endothelial growth factor (anti-VEGF) intravitreal injection (IVI) therapy for neovascular age-related macular degeneration (nAMD) may be alternatively delivered using the Port Delivery Platform (PDP), a drug delivery system surgically inserted into the eye that was re-approved by the U.S. Food and Drug Administration in July 2024. Quantifying the added health benefits and cost consequences of new health interventions is required in various health systems. This study aims to evaluate the cost-effectiveness of universal and targeted use of the PDP with ranibizumab compared to treat-and-extend (T&E) aflibercept injections for patients with nAMD in Norway.

METHODS: We compared the PDP with ranibizumab 100 mg/ml with fixed 24-week refill-exchanges (Q24W) to T&E IVI with vial split aflibercept 2 mg. We developed a probabilistic visual acuity-based simulation model using data derived from published clinical trials and studies. Resources were valued using Norwegian healthcare tariffs and included time and travel costs, in line with Norwegian guidelines. We simulated individuals with nAMD (mean age of 75 years) at treatment initiation and with a best-corrected visual acuity (BCVA) of 71-85 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters. Subgroup analysis simulated individuals undergoing monthly aflibercept treatment, who face long-distance travel times, or who feel extremely anxious about IVI. Main outcomes include total discounted lifetime costs and quality-adjusted life years (QALY) disaggregated by health state, treatment modality, and adverse events. Cost-effectiveness was measured using the incremental cost-effectiveness ratio (ICER) and compared against benchmark thresholds of cost-effectiveness in Norway.

RESULTS: Universal use of the PDP (Q24W) provided greater health benefits (6.5606 QALYs) than aflibercept T&E (6.5516 QALYs) but increased costs by $11,431, yielding an ICER >$1 million per QALY gained, which far exceeds cost-effectiveness thresholds in Norway. In contrast, for patients requiring monthly IVI treatments or facing travel distances of ≥ 4 h, the PDP was considered cost-saving.

CONCLUSIONS: Compared to aflibercept IVIs under a T&E regimen for bilateral nAMD, universal use of the PDP with 24-week refills is unlikely to be considered cost-effective in Norway. However, the PDP may be considered high-value for patients needing frequent IVI or facing long travel distances.

TRIAL REGISTRATION: NA.},
}

Humans
Intravitreal Injections/economics
Cost-Benefit Analysis
*Angiogenesis Inhibitors/administration & dosage/economics
*Recombinant Fusion Proteins/administration & dosage/economics
*Receptors, Vascular Endothelial Growth Factor/administration & dosage
Cost-Effectiveness Analysis
*Ranibizumab/administration & dosage/economics
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Drug Delivery Systems/economics
Female
*Wet Macular Degeneration/drug therapy/economics
Male
Visual Acuity
Aged
Quality-Adjusted Life Years
Aged, 80 and over

@article {pmid42876306,
year = {2026},
author = {Mordà, D and Alibrandi, S and Scimone, C and D'ascola, A and Aliquò, F and Abate, G and Pozzato, G and Scalinci, SZ and D'angelo, R and Sidoti, A and Donato, L},
title = {RNA base-modification and A-to-I editing landscapes of oxidatively stressed human retinal pigment epithelium under Quantum Molecular Resonance electrotherapy and blood-derived secretome.},
journal = {RNA biology},
volume = {23},
number = {1},
pages = {1-27},
doi = {10.1080/15476286.2026.2731889},
pmid = {42876306},
issn = {1555-8584},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Oxidative Stress ; *RNA Editing ; *Adenosine/genetics/metabolism ; *Inosine/genetics/metabolism ; Cell Line ; *RNA/genetics ; },
abstract = {Chemical modifications of RNA bases and adenosine-to-inosine (A-to-I) editing are regulatory layers essentially unexplored in the retinal pigment epithelium (RPE), whose oxidative dysfunction underlies age-related macular degeneration. We mapped both layers in ARPE-19 cells exposed to tert-butyl hydroperoxide under two non-pharmacological interventions, Quantum Molecular Resonance (QMR) electrotherapy and a patient blood-derived secretome, across 56 libraries spanning four arms, three time points and matched stressed and stress-free conditions (GEO: GSE328981). Base modifications were called with HARMLNC and A-to-I editing screened with a transition-signal caller, then re-analysed with REDItools3, JACUSA2 and LoDEI. The high-confidence set comprised 241 calls at 15 sites, all of classes canonical to tRNA and rRNA. The most prevalent was an adenosine modification at chrM:2617 in mitochondrial 16S rRNA (MT-RNR2), detected in 51 of 56 libraries and in every arm. Two positions 1 bp apart lie in an EZR/SYTL3 overlap region, whereas a third chromosome 6 site maps to HLA-C, 127.5 Mb away. No position of either layer differed between treatment arms: 7 testable modification sites (minimum p = 0.19) and, at single-nucleotide resolution under dedicated callers agreeing to r = 0.975-0.992, 15 curated editing positions (minimum q = 0.169). Two one-sided tests bound any change in substitution composition within 1.4% and in mean editing frequency within 10% for secretome and combination and 20% for QMR. Against a stress-free baseline internal to the cohort, only chrM:13710 (MT-ND5) changed detectably (q = 0.03). These layers are therefore small, largely constitutive and quantifiably undisturbed by either intervention at the resolution available.},
}

Humans
*Retinal Pigment Epithelium/metabolism/drug effects
*Oxidative Stress
*RNA Editing
*Adenosine/genetics/metabolism
*Inosine/genetics/metabolism
Cell Line
*RNA/genetics

@article {pmid42876395,
year = {2026},
author = {Saha, T and Frisina, RD and Zhu, X and Park, C and Ding, B and Walton, JP and Bazard, P},
title = {Ergothioneine Mediated Neuroprotective Effects in the Nervous System.},
journal = {Molecular nutrition & food research},
volume = {70},
number = {19},
pages = {e70619},
doi = {10.1002/mnfr.70619},
pmid = {42876395},
issn = {1613-4133},
support = {R21 DC021546-01//NIH-NIDCD/ ; Muench Chairman's Grant 2023//American Hearing Research Foundation/ ; Start-upGrant//Indian Institute of Technology Madras/ ; },
mesh = {*Ergothioneine/pharmacology ; *Neuroprotective Agents/pharmacology ; Humans ; Animals ; Antioxidants/pharmacology ; Neurodegenerative Diseases/drug therapy ; *Nervous System/drug effects ; },
abstract = {Ergothioneine (EGT), a micromolecular derivative of histidine containing sulfur, is found in various organisms, including humans. It demonstrates antioxidant properties, reduces inflammation, and potentially possesses antiaging effects for neurodegenerative conditions, positioning EGT as a potential candidate for health enhancement and healthy aging. EGT appears to offer strong protective properties at the cellular level and shows decreased concentration levels in blood plasma in different neurological conditions such as cognitive impairment, Parkinson's disease, macular degeneration, and other neurodegenerative diseases. Further, emerging evidence from both preclinical and currently limited clinical studies indicates EGT's therapeutic potential for neurological disorders. For instance, EGT treatment slowed the progression of age-related hearing loss and alleviated the cisplatin-induced hearing loss in mouse models, especially in male mice. Similarly, EGT intervention in older adults (aged 60 years or older) has shown some effectiveness in improving cognitive ability, memory, and sleep quality. In this review, we present a thorough examination of its function in neuroprotection, particularly within the nervous system and explore its potential intracellular targeting pathways and their underlying mechanisms.},
}

*Ergothioneine/pharmacology
*Neuroprotective Agents/pharmacology
Humans
Animals
Antioxidants/pharmacology
Neurodegenerative Diseases/drug therapy
*Nervous System/drug effects

@article {pmid42878013,
year = {2026},
author = {Chidlow, G and Wood, JPM and Chan, WO and Casson, RJ},
title = {Evaluation of the Safety and Therapeutic Range of Nanosecond Laser Treatment in Rabbits.},
journal = {Clinical & experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70179},
pmid = {42878013},
issn = {1442-9071},
support = {//Mrs. Barbara O'Connor, Vision Research Foundation, The Royal Adelaide Hospital/ ; },
abstract = {BACKGROUND: Subthreshold, nanosecond laser therapy has potential as a treatment for age-related macular degeneration; however, the therapeutic range and safety profile have not been fully documented. In this study, rabbits were used for a preclinical assessment of nanosecond laser treatment.

METHODS: Adult pigmented rabbits received nanosecond laser treatment at a range of ophthalmoscopically visible and subthreshold energy settings. Various parameters were investigated following laser treatment, namely ophthalmoscopic visibility, haemorrhage, near-infrared (NIR) fundus visibility, angiographic visibility and structure of the retina/retinal pigment epithelium (RPE) as determined by spectral domain optical coherence tomography and post-mortem histology.

RESULTS: Ophthalmoscopically visible energy settings, namely visual effect threshold (VET) and 150% of VET, caused ablation and renewal of targeted RPE cells. These settings presented no vascular damage or Bruch's membrane rupture, but localised photoreceptor loss was evident. A clinically relevant subthreshold energy setting, determined as 50% of VET, likewise caused ablation and renewal of RPE cells. While this setting caused no photoreceptor loss, disruption to segments overlying lesions was evident, which resolved over time. Application of the laser at 25% of VET also caused ablation of RPE cells, while reduction to 12.5% of VET elicited predominantly sublethal injury. The lowest energy setting (8% of VET) had no discernible effect upon RPE cells. The three lower subthreshold energy settings caused no photoreceptor injury.

CONCLUSIONS: Nanosecond laser treatment can be used at lower irradiances than previously employed without causing disruption to photoreceptor segments. The use of this lower energy setting in clinical trials is worthy of consideration.},
}

@article {pmid42878418,
year = {2026},
author = {Bihorel, S and Chiu, J and Chittenden, J and Eissing, T and Turner, KC and Höchel, J and He, ZW and Davis, JD and Harnisch, LO},
title = {Reply to "Aflibercept 8 mg: From Ocular Clearance to Pharmacodynamic Duration".},
journal = {CPT: pharmacometrics & systems pharmacology},
volume = {15},
number = {11},
pages = {e70350},
doi = {10.1002/psp4.70350},
pmid = {42878418},
issn = {2163-8306},
support = {//Regeneron Pharmaceuticals, Inc./ ; //Bayer AG/ ; },
}

@article {pmid42878578,
year = {2026},
author = {Wang, X and Bi, Y and Liu, Y and Nie, Y and Ding, J and Yu, L and Mao, S},
title = {Alpha-Asarone Ameliorates Dry Age-Related Macular Degeneration by Modulating the P2X7/NLRP3 Inflammasome Axis.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {12},
pages = {30},
doi = {10.1167/iovs.67.12.30},
pmid = {42878578},
issn = {1552-5783},
mesh = {Animals ; *NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Male ; Rats ; *Receptors, Purinergic P2X7/metabolism ; Rats, Sprague-Dawley ; *Inflammasomes/metabolism ; Blotting, Western ; Electroretinography ; Disease Models, Animal ; Allylbenzene Derivatives ; Enzyme-Linked Immunosorbent Assay ; *Geographic Atrophy/metabolism/drug therapy ; Tomography, Optical Coherence ; Molecular Docking Simulation ; Humans ; Iodates ; },
abstract = {PURPOSE: To examine whether α-asarone (ASA) protects dry age-related macular degeneration (dAMD) from sodium iodate (SI) injury by modulating the P2X7-mediated NLRP3 inflammasome axis.

METHODS: Male Sprague-Dawley rats were treated with SI to establish a dAMD model. Retinal structure and function were evaluated using electroretinography (ERG), optical coherence tomography (OCT), and hematoxylin-eosin staining, whereas the expression of functional and inflammatory proteins was analyzed via immunofluorescence and Western blotting. Molecular docking, molecular dynamics (MD) simulations, and cellular thermal shift assays (CETSA) were performed to explore the potential interaction between ASA and P2X7. In vitro, SI-stimulated ARPE-19 cells were used to evaluate the protective effects of ASA and the involvement of P2X7 through Cell Counting Kit-8 assays, Annexin V-FITC/PI staining, Fluo-4 staining, YO-PRO-1 uptake detection, ELISA, and Western blotting.

RESULTS: ASA preserved retinal structure and function, maintained the expression of key functional proteins, suppressed microglial activation, and attenuated inflammatory responses. Computational modeling suggested a stable potential interaction between ASA and P2X7, and CETSA further supported ASA-induced modulation of P2X7 thermal stability in cells. In vitro, ASA enhanced cell viability, reduced apoptosis, attenuated Ca²⁺ influx and P2X7 macropore formation, decreased the release of inflammatory cytokines, and downregulated P2X7/NLRP3 pathway, all of which were effectively abolished by activating P2X7.

CONCLUSIONS: The findings demonstrate that ASA mitigates SI-induced dAMD injury by suppressing the P2X7/NLRP3 inflammatory pathway. This study identifies a promising new therapeutic strategy for dAMD.},
}

Animals
*NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
Male
Rats
*Receptors, Purinergic P2X7/metabolism
Rats, Sprague-Dawley
*Inflammasomes/metabolism
Blotting, Western
Electroretinography
Disease Models, Animal
Allylbenzene Derivatives
Enzyme-Linked Immunosorbent Assay
*Geographic Atrophy/metabolism/drug therapy
Tomography, Optical Coherence
Molecular Docking Simulation
Humans
Iodates

@article {pmid42879146,
year = {2026},
author = {Tan, CS and Bakall, B and Koh, AHC and Vakharia, P and Sambhara, D and Maier, M and Mohamed, Q and Yang, M and Margaron, P and Patel, S and Souied, EH},
title = {Variables Associated With Faricimab Treatment Durability in Neovascular Age-Related Macular Degeneration: A Post Hoc Analysis of the TENAYA and LUCERNE Trials.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.4385},
pmid = {42879146},
issn = {2168-6173},
}

@article {pmid42879394,
year = {2026},
author = {Li, R and Yan, M and Huang, Z and Ye, Y and Zhang, X and Song, Y},
title = {Incremental Predictive Value of Month-1 OCT and OCT Angiography for Residual Exudative Activity After Anti-VEGF Loading in Treatment-Naive Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1},
doi = {10.1159/ore/aedag007},
pmid = {42879394},
issn = {1423-0259},
abstract = {INTRODUCTION: During the anti-vascular endothelial growth factor (anti-VEGF) loading phase for neovascular age-related macular degeneration (nAMD), the month-1 follow-up visit represents the earliest standardized imaging time point, yet whether month-1 optical coherence tomography (OCT) and OCT angiography (OCTA) improve prediction of short-term anatomical outcome beyond baseline OCT has not been formally tested. This study quantified the incremental predictive value of month-1 imaging using a nested-model framework that mirrors the sequential clinical workflow.

METHODS: This retrospective, single-center cohort included 124 treatment-naive nAMD eyes from 105 patients that completed three monthly anti-VEGF injections and had evaluable baseline, month-1, and month-3 imaging. Poor anatomical outcome was defined as residual intraretinal fluid and/or subretinal fluid at month 3. Nested generalized estimating equation logistic models accounted for inclusion of bilateral eyes and evaluated baseline OCT variables, the incremental contribution of month-1 structural OCT, and the additional contribution of month-1 OCTA-derived macular neovascularization (MNV) area. Discrimination was assessed using area under the receiver operating characteristic curve (AUC), with ΔAUC confidence intervals estimated by patient-level cluster bootstrap.

RESULTS: At month 3, 47 of 124 eyes (37.9%) had residual exudative activity. In the final model, month-1 central subfield thickness (OR 2.065 per 100-µm increase, 95% CI 1.107-3.853), residual month-1 intraretinal fluid (OR 14.623, 95% CI 3.305-64.703), residual month-1 subretinal fluid (OR 6.975, 95% CI 1.963-24.785), and month-1 MNV area (OR 1.130 per 1-mm² increase, 95% CI 1.030-1.240) were associated with poor month-3 anatomical outcome. AUC improved from 0.742 (95% CI 0.658-0.822) with baseline OCT alone to 0.889 (95% CI 0.828-0.940) after adding month-1 structural OCT (ΔAUC 0.147, 95% CI 0.072-0.226), and to 0.908 (95% CI 0.853-0.952) after adding month-1 MNV area. Baseline-to-month-1 quantitative changes were not associated with outcome.

CONCLUSION: Month-1 structural OCT substantially improved prediction of month-3 residual exudative activity beyond baseline OCT alone, whereas OCTA-derived MNV area contributed modest additional discrimination. These findings identify the first post-treatment imaging visit as an informative point for short-term anatomical risk assessment, but external validation is required before clinical application.},
}

@article {pmid42866554,
year = {2026},
author = {Balian, C},
title = {Comparative Clinical and Therapeutic Landscape of Aflibercept Biosimilars (YESAFILI), High-Dose Aflibercept 8 mg (EYLEA HD), and Faricimab (VABYSMO): A Structured Narrative Review.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {638646},
pmid = {42866554},
issn = {1177-5467},
abstract = {Reference aflibercept 2 mg (EYLEA; Regeneron/Bayer) remains a foundational therapy for neovascular age-related macular degeneration, diabetic macular edema, and macular edema secondary to retinal vein occlusion, supported by high binding affinity for vascular endothelial growth factor (VEGF)-A, VEGF-B, and placental growth factor, along with well-established durability and flexible dosing approaches. The retinal therapeutic landscape is evolving with the introduction of high-dose aflibercept 8 mg (EYLEA HD; Regeneron/Bayer), faricimab (VABYSMO; Roche), and biosimilar aflibercept such as YESAFILI (Biocon Biologics), each representing distinct pharmacologic and clinical strategies. This structured narrative review synthesizes clinical trial and real‑world evidence across these three approaches, with a focus on efficacy, durability, safety, and system-level considerations. A predefined literature search of MEDLINE, Embase, and major ophthalmology conference proceedings was used to identify relevant evidence published from 2015 to 2026. Direct head-to-head evidence among these approaches is limited; therefore, comparisons across separate clinical development programs are descriptive and should be interpreted cautiously. In their respective clinical development programs, high-dose aflibercept and faricimab supported extended dosing intervals with non-inferior visual outcomes relative to standard aflibercept comparators, while biosimilar aflibercept demonstrated clinical equivalence to reference aflibercept with potential economic advantages. Differences remain in long-term real‑world data maturity, safety signal characterization, and implementation considerations. These therapies represent complementary strategies-dose escalation, mechanistic innovation, and molecular equivalence-requiring individualized, evidence-based clinical decision-making in an increasingly complex treatment paradigm.},
}

@article {pmid42867524,
year = {2026},
author = {Zhao, H and Zhang, Q and Shen, J and Fang, Y and Lv, X and Miao, Y and Ma, B and Shuai, S and Hou, Z and Chen, L and Yang, Y and Chen, Q},
title = {A modified chitosan-based inflammation-regulating nanoplatform as a noninvasive carrier for macromolecular ophthalmic drug delivery toward synergistic AMD treatment.},
journal = {Materials horizons},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6mh01360k},
pmid = {42867524},
issn = {2051-6355},
abstract = {Age-related macular degeneration (AMD) is a prevalent cause of irreversible vision loss in the elderly worldwide. Current standard treatment relies on repeated intravitreal injection of anti-vascular endothelial growth factor A (anti-VEGFA), which is associated with invasiveness, poor patient compliance, and variable therapeutic responses. To address this, we developed an ocular-penetrating carrier for topical anti-VEGFA delivery by conjugating eicosapentaenoic acid (EPA) to chitosan (CS), yielding EPA-functionalized chitosan (CS-EPA). Interestingly, CS-EPA retains the antioxidant and anti-inflammatory activities of EPA while enhancing ocular penetration by promoting E-cad redistribution and transient tight-junction modulation. It self-assembles with therapeutic proteins through electrostatic interactions, forming stable nanocomplexes, which can efficiently reach the posterior segment of mice after non-invasive eye drop administration. More importantly, in a laser-induced choroidal neovascularization (CNV) mouse model, CS-EPA/anti-VEGFA eye drops inhibited neovascularization as effectively as intravitreal anti-VEGFA injection. Beyond VEGFA neutralization, CS-EPA directly suppressed the nuclear factor-κB (NF-κB) pathway, reduced pro-inflammatory cytokine production, and alleviated oxidative stress, thereby disrupting the inflammation-angiogenesis cycle driving AMD progression. Therefore, the dual-action CS-EPA, with enhanced ocular penetration and intrinsic anti-inflammatory activity, provides a noninvasive, patient-compliant alternative for AMD treatment and holds promise for treating other posterior segment diseases.},
}

@article {pmid42868766,
year = {2026},
author = {Yang, Z and Yang, J and Ma, S and Tang, G and Xiang, P},
title = {Heavy-metal exposure and ocular diseases: A systematic review integrating exposure biomarkers and mechanistic insights.},
journal = {Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)},
volume = {98},
number = {},
pages = {127967},
doi = {10.1016/j.jtemb.2026.127967},
pmid = {42868766},
issn = {1878-3252},
abstract = {Heavy metals, including lead, cadmium, mercury, and arsenic, are persistent environmental contaminants whose accumulation in ocular tissues represents an underrecognized pathway to visual impairment. This systematic review synthesizes evidence from 2015 to 2026 on the sources, transport, fate, and toxicological effects of heavy metals in the ocular environment. Epidemiological studies suggest associations between chronic exposure and a spectrum of ocular pathologies, including dry eye syndrome, glaucoma, cataract, age-related macular degeneration, diabetic retinopathy, and toxic optic neuropathy. Following environmental release, metals enter the eye through two primary pathways: direct deposition onto the ocular surface from contaminated air, and systemic translocation across blood-ocular barriers. Within ocular tissues, metals exhibit preferential accumulation in melanin-rich structures (retinal pigment epithelium, uveal tract) and avascular compartments (crystalline lens), where they persist due to limited clearance mechanisms. Toxicologically, metals disrupt ocular homeostasis through interconnected molecular mechanisms: oxidative stress via Fenton chemistry and glutathione depletion, inflammatory cascades, mitochondrial dysfunction, enzyme inhibition through sulfhydryl group binding, and disruption of calcium-mediated signaling. Based on this mechanistic understanding, we discuss the contextual implications of source control, exposure biomarkers, chelation, antioxidant strategies, and clinical management; however, the effectiveness of these interventions was not systematically evaluated. This review highlights the need for integrated approaches bridging environmental monitoring, toxicological risk assessment, and clinical ophthalmology.},
}

@article {pmid42868989,
year = {2026},
author = {Patak, L and Belhadj, S and Luz-Madrigal, A and Susaimanickam, PJ and LaPorta, JM and Tsai, TH and Xie, R and Gayet, J and Baez, HC and Fischer, WS and Hollar, R and Foley, N and Campbell, AL and Gong, S and Ma, Z and Maminishkis, A and Bharti, K and Amaral, J and Gullapalli, VK and DiLoreto, DA and Gamm, DM and Puthussery, T and McGregor, JE},
title = {Photoreceptor replacement therapy using a tissue scaffold shows evidence of donor-host integration in non-human primate retina.},
journal = {Stem cell reports},
volume = {21},
number = {10},
pages = {103079},
doi = {10.1016/j.stemcr.2026.103079},
pmid = {42868989},
issn = {2213-6711},
mesh = {Animals ; Humans ; *Tissue Scaffolds/chemistry ; *Retinal Degeneration/therapy/pathology ; *Retina/cytology ; *Photoreceptor Cells, Vertebrate/transplantation/metabolism ; Retinal Bipolar Cells/metabolism ; },
abstract = {Retinal degeneration is characterized by progressive photoreceptor (PR) loss, leading to visual impairment and ultimately blindness. PR replacement is a promising therapeutic strategy, but surgical delivery remains challenging, and efficacy in primates remains unknown. Tissue scaffolds hold potential for better control over cell delivery and distribution. Here, we delivered a scaffold, loaded with human embryonic stem-cell-derived PR precursors (PRPs), to the subretinal space of a non-human primate (NHP) and monitored donor PR survival and morphology in vivo. A substantial fraction of donor PRs survived for 20-weeks, with neurite extension by week 7 and some morphological elongation by week 17. Immunolabeling confirmed donor PR survival at 20 weeks with expression of key phototransduction and ribbon proteins, and some donor PRs forming putative synapses with host bipolar cells (BCs), including midget BCs. These findings suggest that scaffold-mediated PR replacement holds promise for restoring high acuity foveal vision.},
}

Animals
Humans
*Tissue Scaffolds/chemistry
*Retinal Degeneration/therapy/pathology
*Retina/cytology
*Photoreceptor Cells, Vertebrate/transplantation/metabolism
Retinal Bipolar Cells/metabolism

@article {pmid42870487,
year = {2025},
author = {Thapa, R and Ruit, S and Poudel, M and Neupane, P and Banjara, P and Duwal, S and Gurung, E and Tabin, GC},
title = {Awareness, Knowledge, and Practice on Retinal Diseases at High-altitude of Nepal.},
journal = {Nepalese journal of ophthalmology : a biannual peer-reviewed academic journal of the Nepal Ophthalmic Society : NEPJOPH},
volume = {17},
number = {34},
pages = {45-56},
doi = {10.3126/nepjoph.v17i34.68246},
pmid = {42870487},
issn = {2091-0320},
mesh = {Humans ; Nepal/epidemiology ; Cross-Sectional Studies ; Female ; *Health Knowledge, Attitudes, Practice ; Male ; *Retinal Diseases/epidemiology ; Middle Aged ; *Altitude ; Adult ; Prevalence ; Aged ; *Awareness ; },
abstract = {INTRODUCTION: Retinal disorders are the major causes of visual impairment in Nepal. Limited access to eye care service in high altitude regions, along with low awareness and knowledge on the retinal diseases delays timely treatment and care.

OBJECTIVE: To assess the awareness, knowledge, and practices on major retinal disorders at high-altitude in Nepal.

METHODOLOGY: An analytical cross-sectional study was carried out to assess the retinal disease prevalence at three high-altitude districts of Nepal namely Manang, Mustang, and Solukhumbu from 2023 May to 2023 July after ethical clearance. The sample size of 308 with the age 40 years and above were included with random sampling. Awareness, knowledge, and practice on major retinal disease on diabetic retinopathy (DR), age-related macular degeneration (AMD), hypertensive retinopathy (HR), and high-altitude retinopathy (HAR) were assessed. Facetoface interviews were conducted after obtaining informed written consent. Ethical approval was granted by the Nepal Health Research Council, and data were analysed using IBM SPSS v.20.

RESULT: A total of 338 study participants were enrolled. The mean age was 56.98±11.13 years with female preponderance (216, 63.9%). Three-fifth (61.8%) were literate. Awareness was found among 131 (38.76%) on diabetes mellitus affecting eye, 19 (5.6%) on AMD, 118 (34.9%) on hypertension affecting eye, and 273 (80.8%) on high-altitude affecting eye. However, only five (1.5%) were aware that high-altitude could affect retina and none were aware of its preventive measures. Eleven (33.3%) of people with diabetes had regular eye exams. One respondent had AMD, however he did not receive frequent eye examinations. Only eight (8.3%) of those with hypertension had undergone regular eye check-ups.

CONCLUSION: The awareness, knowledge, and practice on major retinal diseases including high-altitude retinopathy was low among the population of high-altitude in Nepal. Emphasis should be given on raising awareness activities besides enhancing the access to eye care services.},
}

Humans
Nepal/epidemiology
Cross-Sectional Studies
Female
*Health Knowledge, Attitudes, Practice
Male
*Retinal Diseases/epidemiology
Middle Aged
*Altitude
Adult
Prevalence
Aged
*Awareness

@article {pmid42870606,
year = {2026},
author = {Pu, J and He, J and Xue, R and Gao, R and Xiao, Y and Xu, W and Wan, H},
title = {Ocular Distribution and Metabolite Profiling of Vorolanib in Rats and Its In Vitro Metabolism Using Human Recombinant Enzymes.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683261496831},
doi = {10.1177/10807683261496831},
pmid = {42870606},
issn = {1557-7732},
abstract = {PURPOSE: Vorolanib is a multitarget tyrosine kinase inhibitor with anti-angiogenic potential for diabetic macular edema (DME) and neovascular age-related macular degeneration (wAMD), but its ocular disposition and metabolism are unclear. This study investigated the cytochrome P450 (CYP) phenotyping, ocular distribution, and metabolite profiles of vorolanib in rats.

METHODS: Male Sprague-Dawley rat (SD rats) received a single intravenous (IV) (2 mg/kg) or oral (50 mg/kg) vorolanib. Drug concentrations in plasma and ocular tissues were measured by liquid chromatography-tandem mass spectrometry. Metabolic contribution of recombinant human CYPs (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4) was assessed, and metabolites were identified by LC-high-resolution mass spectrometry.

RESULTS: Recombinant human CYP3A4 was the predominant metabolizing enzyme, accounting for 85.6% of intrinsic clearance (CLint = 3.76 µL/min/pmol), followed by CYP2C8 (10.6%). Vorolanib exhibited high IV clearance but achieved higher concentrations in the cornea, retina, and plasma within 4 h after oral administration. Fourteen metabolites (M1-M14) were identified in plasma, and eight were detected in ocular tissues. M9 (mono-oxygenation/reduction) and M10 (N-demethylation) were major in the cornea and retina after oral dosing. Recombinant human CYP3A4 primarily generated M2, M9, M10, M11, and M12, while CYP2C8 contributed to M2 and M9. Major pathways included mono-oxygenation, N-demethylation, reduction, dehydrogenation, and glucuronidation.

CONCLUSIONS: Vorolanib is extensively metabolized by CYP3A4 and CYP2C8 in humans, and both the parent compound and its metabolites are widely distributed to ocular tissues in rats. The detection of multiple metabolites in these tissues emphasizes the need to consider both the parent drug and its active metabolites when evaluating ophthalmic efficacy and safety.},
}

@article {pmid42873080,
year = {2026},
author = {Sharma, A and Wu, L and Bloom, S and Baldwin, G and Miller, JB and Miller, JW and Lesmes, LA and Gupta, R and MacCumber, MW and Upadhyaya, A and Upadhyay, AM and Singh, DV and Rezaei, KA},
title = {RWC Update: Is Visual Acuity Still the Right Primary Endpoint in Age-related Macular Degeneration?; Black Cataract; Radiation Retinopathy.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {57},
number = {10},
pages = {615-618},
doi = {10.3928/23258160-20260921-01},
pmid = {42873080},
issn = {2325-8179},
}

@article {pmid42873269,
year = {2026},
author = {Dithmar, S and Lipsky, T and Schargel-Cabezon, E and Birtel, J and Hoyng, C and Charbel Issa, P and Kellner, U and Stingl, K and Holz, FG and Pfau, K and Pfau, M},
title = {[Stargardt disease (ABCA4-asssociated retinopathy): Overview of clinical aspects, classification and differential diagnoses].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42873269},
issn = {2731-7218},
abstract = {Morbus Stargardt (STGD1) is the most common autosomal recessive macular dystrophy and is caused by biallelic variants in the ABCA4 gene located on chromosome 1. More than 1200 disease-associated variants have been described, causing a broad phenotypic spectrum. The hallmark feature is a bilateral, typically slowly progressive visual impairment, although best-corrected visual acuity can be preserved for a long time in patients with foveal sparing. The disease is characterized by lipofuscin accumulation in the retinal pigment epithelium, manifesting as fundus flavimaculatus on funduscopic examination, outer retinal atrophy on optical coherence tomography (OCT) and a characteristic pattern on fundus autofluorescence imaging. While earlier classifications were primarily based on clinical and electrophysiological criteria, current approaches increasingly focus on genotype-phenotype correlations, which can also enable prognostic statements. Severe, early-onset disease courses are predominantly associated with loss of function variants, whereas certain genotypes have been linked to milder and later-onset manifestations. The differential diagnosis remains challenging due to considerable phenotypic overlap with other autosomal-dominant and autosomal-recessive macular dystrophies. Moreover, particularly in late-onset cases, differentiation from geographic atrophy secondary to age-related macular degeneration can be necessary.},
}

@article {pmid42874330,
year = {2026},
author = {Keskin, T and Tural, S and Yucel, OE},
title = {The synergistic effects of resveratrol and nicotinamide on cell proliferation, apoptosis, and SIRT1 gene expression in human retinal pigment epithelial cells.},
journal = {Tissue & cell},
volume = {104},
number = {Pt 3},
pages = {104035},
doi = {10.1016/j.tice.2026.104035},
pmid = {42874330},
issn = {1532-3072},
abstract = {The aim of our study is to evaluate the effects of Resveratrol and Nicotinamide on cell proliferation, viability, apoptosis and SIRT1 gene expression in human retinal pigment epithelial cells (RPE), with relevance to age-related macular degeneration (AMD). Healthy RPE cells were exposed to moderate oxidative stress, then treated with resveratrol (50-100-150 μmol/L) and nicotinamide (1-5-10 mM/L), both separately and in combination, for 24, 48, and 72 h. Morphological changes and cell density were examined using inverted microscopy to complement functional data. The most significant results were achieved with 72 h of combined treatment with 100 μmol/L resveratrol and 1 mM/L nicotinamide, showing increased cell viability and proliferation (p < 0.001), decreased apoptosis+necrosis values (p < 0.001), and elevated SIRT1 expression (p < 0.001). This combination was non-cytotoxic to healthy RPE cells (p > 0.05) and more effective than separate treatments. The combined application caused SIRT1 gene expression levels similar to healthy controls (p > 0.05). To confirm functional dependency on SIRT1, targeted gene silencing was performed using SIRT1 siRNA. Compared to the negative control group, SIRT1 silencing resulted in a 25.58-fold downregulation of SIRT1 mRNA, accompanied by a 5.28-fold upregulation of pro-apoptotic Bax and a 3.91-fold downregulation of anti-apoptotic Bcl-2 (p < 0.001), effectively reversing the cytoprotective effects of the co-treatment. These findings demonstrate that RV+NAM co-treatment exerts robust synergistic protection against oxidative stress-induced apoptosis in RPE cells through SIRT1-dependent mechanism, offering a promising therapeutic strategy for dry AMD. This is the first study to investigate the effects of this specific dose combination in a dry AMD model.},
}

@article {pmid42861422,
year = {2026},
author = {Beheshti, SO and Larsen, M and Nordestgaard, BG and Afzal, S},
title = {Higher plasma vitamin D levels are not causally associated with less age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70253},
pmid = {42861422},
issn = {1755-3768},
support = {//Gangstedfonden/ ; //Copenhagen University Hospital-Herlev and Gentofte Hospital/ ; //Overlæge Johan Boserup og Lise Boserups Legat/ ; //KV Fonden/ ; //Henry og Astrid Møllers Fond/ ; //Aase og Ejnar Danielsens Fond/ ; },
abstract = {PURPOSE: Higher levels of plasma 25-hydroxyvitamin D have been associated with a lower risk of age-related macular degeneration (AMD). We investigated observational and potential causal associations of plasma 25-hydroxyvitamin D with the risk of AMD in two large contemporary population-based prospective studies and a genetic case-control consortium.

METHODS: Observationally, we studied 25 445 individuals with measured baseline plasma 25-hydroxyvitamin D (536 incident AMD events) in the Copenhagen General Population Study (CGPS) and 372 477 individuals (7842 incident AMD events) in the UK Biobank using Cox regression analysis for hazard ratios. Causally, we studied 107 793 individuals (1474 incident AMD events) in the CGPS, 406861 individuals (9183 incident AMD events) in the UK Biobank and 31 858 individuals (17 411 AMD cases) in the International AMD Genomics Consortium with genetic variants leading to life-long elevated plasma 25-hydroxyvitamin D. These genetic variants were combined to plasma 25-hydroxyvitamin D-increasing unweighted and weighted allele scores and genetic associations to AMD risk were tested using Cox regression and logistic regression for hazard ratios and odds ratios.

RESULTS: Observationally, higher plasma 25-hydroxyvitamin D was associated with higher AMD risk in CGPS and lower risk in UK Biobank. Genetically, each increase in the 25-hydroxyvitamin D-increasing weighted CGPS allele score was associated with a hazard ratio of 1.01 (95% confidence interval: 1.00-1.02) in CGPS, with similar results in the other studies.

CONCLUSION: These findings do not support a causal role of plasma 25-hydroxyvitamin D in the risk of AMD.},
}

@article {pmid42862101,
year = {2026},
author = {Feo, A and Patel, A and Afzali, M and Faghihi, S and Sarraf, D},
title = {LAMELLAR MACULAR HOLE AFTER ACQUIRED VITELLIFORM LESION COLLAPSE IN INTERMEDIATE AGE-RELATED MACULAR DEGENERATION.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000005034},
pmid = {42862101},
issn = {1539-2864},
}

@article {pmid42862818,
year = {2026},
author = {Loewenstein, A and Zinkernagel, M and Schlingemann, RO and Bandello, F and Boon, CJ and Schmidt-Erfurth, U and Eter, N and Klaver, CC and Udaondo, P and Zweifel, SA and Tufail, A and Holz, FG},
title = {Updated guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA).},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1},
doi = {10.1159/oph/aeeag010},
pmid = {42862818},
issn = {1423-0267},
abstract = {Since the publication in 2014 of the original EURETINA guidelines for the management of neovascular age-related macular degeneration (nAMD), the treatment landscape for this prevalent and potentially devastating condition has evolved substantially. Along with the introduction of new anti-vascular endothelial growth factor (anti-VEGF) agents and the release of biosimilar agents, anti-VEGF dosing strategies have been refined, and increasing amounts of clinical trial and real-world evidence are available to inform practice. To provide an updated European perspective on nAMD management, the EURETINA panel systematically reviewed European guidelines published since 2014 alongside recent randomized controlled trials and other relevant evidence. Areas of broad consensus across guidelines were identified, including the importance of early diagnosis and prompt initiation of anti-VEGF therapy, and the central role of optical coherence tomography (OCT) in both diagnosis and monitoring. Treat-and-extend regimens are now established as the preferred approach for retreatment, with disease activity defined primarily by changes in retinal fluid accumulation detected by OCT imaging. Recommendations also address follow-up, switching or discontinuing therapy, and referral to low vision support services. Incorporating the EURETINA panel's expertise into this synthesis, this update to the EURETINA guidelines for nAMD provides recommendations to guide high-quality, evidence-based care for patients with nAMD across Europe.},
}

@article {pmid42863967,
year = {2026},
author = {Jonas, JB and Panda-Jonas, S and Pan, Z and Xu, J and Jonas, RA and Wang, YX},
title = {Ellipsoid zone defects in age-related macular degeneration: the Beijing Eye Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327829},
pmid = {42863967},
issn = {1468-2079},
}

@article {pmid42865394,
year = {2026},
author = {Rossi, S and Gesualdo, C and Trotta, MC and Perrotta, R and D'Agostino, FA and Sabbatino, D and Gerosolima, C and Casaburi, R and Simonelli, F},
title = {Real-world anatomical and functional outcomes following Faricimab therapy in neovascular age-related macular degeneration: a one-year observational study.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1901385},
pmid = {42865394},
issn = {2296-858X},
abstract = {INTRODUCTION: This study evaluated 12-month anatomical and functional outcomes of Faricimab in Italian patients with neovascular age-related macular degeneration (nAMD).

METHODS: 30 eyes from 30 participants who completed the 12-month follow-up were retrospectively analyzed at "Luigi Vanvitelli" University Eye Clinic (Naples) and "Rummo" Hospital Ophthalmology Unit (Benevento). All underwent best-corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA). Patients were stratified by anti-vascular endothelial growth factor (VEGF) treatment [naïve (N = 22); non-naïve (N = 8)], baseline macular neovascularization (MNV) type and fluid distribution. BCVA and central retinal thickness (CRT) were assessed at 6 and 12 months. The association between baseline subretinal hyperreflective material (SHRM) status and longitudinal BCVA and CRT was also investigated.

RESULTS: The intravitreal injection number was similar between naïve and non-naïve eyes (median, 6 vs. 7; p = 0.093). One adverse event (vitreitis with ocular hypertension) occurred. Mixed-effects modelling showed significant longitudinal improvements in BCVA from baseline to months 6 and 12, with no significant time-by-treatment-history interaction. Baseline retinal fluid distribution was not significantly associated with differences in BCVA changes, while baseline SHRM status showed a significant time-by-SHRM interaction for BCVA, although multiplicity-adjusted between-group comparisons were not significant at any time point. CRT decreased significantly from baseline to months 6 and 12, whereas the change between months 6 and 12 was not statistically significant. SHRM thickness also decreased significantly from baseline to months 6 and 12. Exploratory analyses by MNV subtype did not identify significant differences in 12-month BCVA or CRT. In exploratory multivariable analysis, baseline BCVA was the only factor significantly associated with 12-month BCVA, whereas age, previous anti-VEGF treatment, and baseline SHRM were not.

DISCUSSION: This retrospective two-center study showed significant improvements in BCVA and CRT after 12 months of Faricimab, with no statistically detectable difference in longitudinal BCVA according to previous anti-VEGF exposure. Although baseline SHRM was associated with a significant time-by-SHRM interaction for BCVA, the absence of significant multiplicity-adjusted between-group differences limits interpretation of a differential response according to SHRM status. Given the small sample size and retrospective design, these findings should be interpreted cautiously.},
}

@article {pmid42855777,
year = {2026},
author = {, },
title = {[Chinese expert consensus on high-dose anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (2026)].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {62},
number = {10},
pages = {792-805},
doi = {10.3760/cma.j.cn112142-20260525-00227},
pmid = {42855777},
issn = {0412-4081},
mesh = {Humans ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; China ; *Choroidal Neovascularization/drug therapy ; Intravitreal Injections ; *Macular Degeneration/drug therapy ; Ranibizumab/administration & dosage ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is primarily characterized by the formation of abnormal choroidal neovascularization and can lead to substantial visual impairment. Intravitreal administration of anti-vascular endothelial growth factor (anti-VEGF) agents has become the standard first-line treatment for nAMD. However, challenges remain, including the need for frequent injections, considerable treatment burden, and suboptimal responses in a subset of patients. In recent years, the emergence of high-dose anti-VEGF therapies has provided a novel strategy for extending treatment intervals and optimizing long-term disease management. To address these clinical needs, the Ophthalmology Group of China Alliance for Rare Diseases/Beijing Society of Rare Disease Clinical Care and Accessibility organized a multidisciplinary panel of experts to develop this consensus. Based on the latest evidence-based medical findings, together with international guidelines and the realities of clinical practice in China, a standardized consensus-development methodology was employed. Consensus recommendations were formulated for eight key clinical questions regarding the use of high-dose anti-VEGF therapies in the treatment of nAMD. The aim of this document is to provide evidence-based guidance and clinical reference for the standardized application of high-dose anti-VEGF therapies in nAMD, thereby further improving the quality of standardized diagnosis, treatment, and long-term management of nAMD in China.},
}

Humans
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
China
*Choroidal Neovascularization/drug therapy
Intravitreal Injections
*Macular Degeneration/drug therapy
Ranibizumab/administration & dosage
*Vascular Endothelial Growth Factor A/antagonists & inhibitors

@article {pmid42857105,
year = {2026},
author = {Han, JW and Yang, JY and Kim, Y and An, S and Yoo, E and Park, IH and Lee, SW and Lee, HJ and Lee, TG and Jung, WH and Park, HS and Kim, JH and Choi, JS and Chang, HS and Park, TK},
title = {rAAV-mediated multi-miRNA delivery targeting MAPK pathway suppresses laser-induced choroidal neovascularization in mice.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {4},
pages = {103101},
pmid = {42857105},
issn = {2162-2531},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, with neovascular AMD (nAMD) characterized by choroidal neovascularization (CNV) and subretinal fibrosis. Although anti-VEGF therapy is the current standard, frequent injections and limited efficacy necessitate alternative treatments. The mitogen-activated protein kinase (MAPK) pathway contributes to AMD by promoting oxidative stress-induced apoptosis, inflammation, and angiogenesis. We evaluated the therapeutic potential of MAPK-targeting microRNAs (miRNAs) delivered via recombinant adeno-associated virus (rAAV). Two rAAV2.7m8-based strategies were developed: a MAPK-miR mixture (three individually packaged miRNAs: hsa-miR-122-5p, let-7a-5p, and miR-26a-5p) and an MAPK-miR tandem (all three miRNAs in one vector under separate U6 promoters). Both formulations effectively inhibited MAPK activation in oxidative stress-induced RPE cells and laser-induced CNV mouse models. Treatment reduced CNV leakage and angiogenesis, as confirmed by fluorescein angiography and histology. The MAPK-miR mixture showed enhanced efficacy in suppressing epithelial-mesenchymal transition (EMT) and subretinal fibrosis. This study demonstrates the therapeutic benefit of rAAV-mediated multi-miRNA delivery targeting MAPK signaling in AMD. Sustained expression from rAAV vectors may overcome the limitations of anti-VEGF therapy, offering a novel gene therapy approach for nAMD. Further optimization and safety evaluation are warranted for clinical translation.},
}

@article {pmid42857796,
year = {2026},
author = {Alam, I and Hussain, A and Agrawal, DK},
title = {Organelle Crosstalk: Mitochondria and Endoplasmic Reticulum in Macular Degeneration.},
journal = {Journal of ophthalmology and research},
volume = {9},
number = {3},
pages = {60-67},
pmid = {42857796},
issn = {2644-0024},
support = {R25 AI179582/AI/NIAID NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss characterized by progressive retinal pigment epithelium (RPE) dysfunction, mitochondrial damage, oxidative stress, and chronic inflammation. While mitochondrial dysfunction is a known contributor to AMD, the contribution of the endoplasmic reticulum (ER) has not been fully explored. Mitochondrial associated membranes (MAMs) are regions of the mitochondria which are in direct contact with the ER and are critical areas for regulating essential cellular functions including calcium signaling, mitochondrial dynamics, and apoptosis. Dysfunction of these critical sites may lead to progressive retinal degeneration through the production of reactive oxygen species (ROS), calcium overload, and inflammasome activation in RPE cells. The study was conducted as a comprehensive critical review article on the subject. Findings are reported on the connection between the mitochondria and ER, specifically through MAM dysfunction, in macular degeneration. Overall, this critical review article discusses the pathophysiology of macular degeneration with the mechanistic insights into MAM deregulation and decoding the structural and functional breakdown of MAMs. Understanding the role of MAM-mediated signaling in AMD may identify potential therapeutic targets aimed at restoring mitochondrial resilience and retinal homeostasis.},
}

@article {pmid42858823,
year = {2026},
author = {Chatra, N and Nabavi, A and Swaminathan, SS and Medeiros, FA and Yousefi, S},
title = {Association of ophthalmic disease and physical activity in All of Us Research Program.},
journal = {Journal of sport and health science},
volume = {},
number = {},
pages = {101182},
doi = {10.1016/j.jshs.2026.101182},
pmid = {42858823},
issn = {2213-2961},
abstract = {BACKGROUND: The association between physical activity (PA) and ophthalmic disease remains uncertain, as most studies relied on self-report. This study aimed to evaluate the associations between long-term, objectively measured PA by wearable devices (Fitbit) and the incidence and prevalence of common ophthalmic diseases in the All of Us Research Program.

METHODS: We conducted cross-sectional and longitudinal analyses of 14,757 adults with electronic health record (EHR) and Fitbit data. Participants had at least 6 months of valid Fitbit wear (≥10 h/day and ≥100 steps/day). The cohort had a mean age of 55.0 ± 15.7 years (mean ± SD); 70.4% were female, and 79.1% were White. Mean daily step counts and minutes of moderate-to-vigorous physical activity (MVPA) were evaluated in relation to age-related macular degeneration (AMD), diabetic retinopathy (DR), primary open-angle glaucoma (POAG), and senile cataract identified using International Classification of Diseases codes. Logistic regression estimated odds ratios (ORs) for prevalent disease, and Cox proportional hazards models estimated hazard ratios (HRs) for incident disease. Models were adjusted for age, sex, race, and body mass index. DR analyses were also restricted to participants with diabetes mellitus.

RESULTS: In cross-sectional analyses, higher PA was significantly associated with lower odds of DR among participants with DM (steps per 1000: OR = 0.91, 95% confident interval (95%CI): 0.86-0.95; p < 0.001; MVPA per 10 min: OR = 0.87, 95%CI: 0.82-0.93; p < 0.001). No significant cross-sectional associations were observed between PA and AMD, POAG, or senile cataract. In longitudinal analyses, higher PA predicted a lower risk of incident DR among participants with DM (steps: HR = 0.93, 95%CI: 0.87-0.99; p = 0.022; MVPA: HR = 0.86, 95%CI: 0.79-0.93; p < 0.001). No significant longitudinal associations were found between PA and AMD, POAG, or senile cataract.

CONCLUSION: Our findings suggest a strong inverse association between sustained PA and incident DR and underscore the value of long-term wearable data for ophthalmic research.},
}

@article {pmid42858861,
year = {2026},
author = {Li, S and Yang, Q and Zhu, Y and Li, T and Scherman, D and Li, W and Chen, Z and Shi, S and Li, H and Zou, L},
title = {Glycocalyx-binding and cell-penetrating peptide-modified nanomicelles for enhanced ocular delivery of quercetin and retinal protection in a dAMD model.},
journal = {International journal of pharmaceutics},
volume = {},
number = {},
pages = {127512},
doi = {10.1016/j.ijpharm.2026.127512},
pmid = {42858861},
issn = {1873-3476},
abstract = {Dry age-related macular degeneration (dAMD) is a highly prevalent degenerative retinal disease. Quercetin, a bioactive ingredient in traditional Chinese medicine, can mitigate the oxidative stress that helps drive dAMD; however, its low water solubility and poor corneal permeability limit its efficacy. We developed dual-functional polymeric micelles (PMs) co-conjugated with a glycocalyx-binding peptide (GBP) and a cell-penetrating peptide (TAT) for the enhanced topical ocular delivery of quercetin (QUE), named GT-PMs/QUE. The GT-PMs/QUE exhibited a particle size of 46.25 ± 3.05 nm and a zeta potential of -5.64 ± 0.92 mV. GT-PMs exhibited significantly higher cellular uptake efficiency than the unmodified group (PMs) and single-peptide modified groups (GBP-PMs and TAT-PMs). In the sodium iodate-induced oxidative damage model of adult retinal pigment epithelial cell line-19 (ARPE-19) cells, the GT-PMs/QUE treatment group showed significantly reduced ROS and MDA levels along with markedly increased SOD, CAT, and GSH activities that approached normal control levels compared to the model group. In a mouse model of dAMD, GT-PMs/QUE greatly improved the bioavailability of quercetin delivered via eye drop administration and attenuated sodium iodate-induced retinal damage. This study provides a theoretical and experimental basis for enhanced ocular delivery of quercetin and protection against dAMD-related retinal damage.},
}

@article {pmid42853059,
year = {2026},
author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Wang, YX and Nangia, V and Panda-Jonas, S},
title = {Probability of myopic macular degeneration in dependence on axial length and age: The two-continent eye study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70241},
pmid = {42853059},
issn = {1755-3768},
abstract = {PURPOSE: To assess the probability of myopic macular degeneration (MMD).

METHODS: The project included four population-based investigations: Beijing Eye Study (BES) (n = 3325; age: 50+ years), Ural Eye and Medical Study (UEMS) (n = 5586 participants; age: 40+ years), Ural Very Old Study (UVOS) (n = 541;age: 85+ years) and Central India Eye and Medical Study (CIEMS) (n = 4467; age: 30+ years). MMD was defined according to the Meta-analysis for Pathologic Myopia Study Group. Based on binary regression analyses, probability equations were formulated.

RESULTS: The total study population (27 607 eyes; 14 108 individuals) was randomly divided in a ratio of 1:1 into a development subgroup for the probability score development and into a validation subgroup. In the validation subgroup, the probability assessment for MMD stage 2+ and 3+ had an area under the receiver operating characteristic curve of 0.996 and 0.998, respectively. Applying the probability equations, MMD stage 2+ probability for myope with an axial length of 28 and 30 mm increased from age 30 to 75 years from 55.0% to 88.1% and from 99.3% to 99.8%, respectively. MMD stage 3+ probability at an axial length of 28 and 30 mm increased from age 30 to 75 years from 8.3% to 57.5% and from 81.8% to 98.5%, respectively.

CONCLUSIONS: The MMD probability assessment offers a rough estimate of the MMD probability at present and at older age, based on axial length and age. For an axial length of 28 and 30 mm, the probability of MMD stage 3+ at 75 years was 57.5% and 98.5%, respectively.},
}

@article {pmid42853158,
year = {2026},
author = {Chen, X and Wang, YX},
title = {Statins and Age-Related Macular Degeneration: From a Class Effect to a Specific Hypothesis.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.09.008},
pmid = {42853158},
issn = {2468-6530},
}

@article {pmid42853354,
year = {2026},
author = {Brown, DM and Rao, R and Berliner, AJ and Patel, D and Cheng, Y and Bai, Z and Wykoff, CC},
title = {Study Design for ELARA, a Phase 3b Trial of Aflibercept 8 mg in Previously Treated Patients With Neovascular Age-Related Macular Degeneration or Diabetic Macular Edema.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42853354},
issn = {2193-8245},
abstract = {INTRODUCTION: Aflibercept 8 mg at extended dosing intervals demonstrated functional and anatomic improvements in a large majority of patients with neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME) in pivotal trials. Although a subset of patients may require frequent injections to maintain disease control, the efficacy and safety of monthly dosing with aflibercept 8 mg had not been extensively assessed. The ELARA trial evaluated the tolerability and measures of efficacy of aflibercept 8 mg every 4 weeks, as well as the feasibility of dosing interval extension following 6 monthly doses of aflibercept 8 mg, in previously treated patients with nAMD or DME.

METHODS: ELARA was a multicenter, open-label, 96-week, phase 3b trial. Previously treated patients with nAMD or DME who received ≥ 3 intravitreal anti-vascular endothelial growth factor injections within 5 months before the first trial visit were eligible to participate. Patients received monthly injections of aflibercept 8 mg through week 24. Beginning at week 24, a treat-and-extend regimen was implemented based on dose regimen modification (DRM) criteria assessing disease activity and response to treatment to reflect treatment patterns of retina specialists in clinical practice. Dosing intervals were modified in patients who met DRM criteria for extension or shortening from week 24 through 96. The minimum dosing interval was every 4 weeks.

PLANNED OUTCOMES: The primary outcome was the incidence of ocular and non-ocular treatment-emergent adverse events through week 24. Exploratory outcomes included the change from baseline in best-corrected visual acuity and central subfield thickness at weeks 24 and 96.

TRIAL REGISTRATION: NCT06491914.},
}

@article {pmid42855241,
year = {2026},
author = {Dave, S and Binns, AM and Vinuela-Navarro, V and Callaghan, T},
title = {What is the patient experience of receiving lifestyle advice regarding age-related macular degeneration (AMD) in secondary eye care? A multimethods study.},
journal = {BMJ open},
volume = {16},
number = {10},
pages = {e118134},
doi = {10.1136/bmjopen-2026-118134},
pmid = {42855241},
issn = {2044-6055},
}

@article {pmid42849000,
year = {2026},
author = {Nunns, B and Singh, A and Ah-Chan, J},
title = {Longer-term outcomes of intravitreal therapy for neovascular age-related macular degeneration at a peripheral centre (Palmerston North eye clinic).},
journal = {The New Zealand medical journal},
volume = {139},
number = {1643},
pages = {24-31},
doi = {10.26635/6965.7545},
pmid = {42849000},
issn = {1175-8716},
mesh = {Humans ; Female ; Retrospective Studies ; Male ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; New Zealand ; Aged ; Visual Acuity ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Aged, 80 and over ; *Macular Degeneration/drug therapy ; *Ranibizumab/therapeutic use/administration & dosage ; Treatment Outcome ; *Bevacizumab/therapeutic use/administration & dosage ; },
abstract = {AIM: The aim of this study was to evaluate long-term real-world outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) at a regional New Zealand centre, with a primary focus on treatment duration and reasons for cessation.

METHODS: A retrospective cohort study was conducted at Palmerston North eye clinic, including all newly diagnosed eyes with nAMD initiating anti-VEGF therapy between November 2017 and August 2023. Demographic data, visual acuity, treatment duration and documented reasons for cessation were extracted from a prospectively maintained database and validated against electronic health records.

RESULTS: Among 527 eyes from 446 patients, 39.8% ceased treatment. The most common reasons were end-stage disease (44.8%), patient death (21.9%), logistical factors (17.6%) and injection intolerance (8.1%). Mean treatment duration was 421 days. Visual outcomes were favourable overall with 20.2% of eyes improving and 59.5% remaining stable. Better baseline visual acuity strongly predicted better final vision.

CONCLUSIONS: High early cessation due to end-stage disease suggests possible late presentation, underscoring the need for earlier detection and referral. Addressing logistical barriers and supporting adherence will be increasingly important as demand for anti-VEGF therapy grows with an ageing population.},
}

Humans
Female
Retrospective Studies
Male
Intravitreal Injections
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
New Zealand
Aged
Visual Acuity
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Aged, 80 and over
*Macular Degeneration/drug therapy
*Ranibizumab/therapeutic use/administration & dosage
Treatment Outcome
*Bevacizumab/therapeutic use/administration & dosage

@article {pmid42850292,
year = {2026},
author = {Ansari, G and Janeschitz-Kriegl, L and De Angeli, P and Gliem, M and Wang, M and Pfau, K and Michalakis, S and Kohl, S and György, B and Pfau, M},
title = {[Genetic therapies for Stargardt disease].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42850292},
issn = {2731-7218},
abstract = {Stargardt disease is caused by biallelic variants in the ABCA4 gene and is the most frequent autosomal recessive macular degeneration in childhood and adolescence. No approved disease-modifying treatment has yet been approved. The size of the ABCA4 gene represents a challenge for conventional gene therapy based on adeno-associated viruses (AAV) and was the stimulus for the development of innovative strategies. Gene supplementation therapies use lentiviral or dual AAV vectors to introduce complete copies of the healthy ABCA4 gene into the target cells, whereas gene editing procedures, such as RNA exon editing or base editing, enable direct correction of the mutations causing the diseases. Intravitreal injection of antisense oligonucleotides selectively addresses splicing defects and provides a less invasive intravitreal approach but requires repeated applications. Indirect therapies modulate the visual cycle or neuroprotective signalling pathways and can be applied independent of variants. Finally, disease-agnostic approaches, such as optogenetics, enable restoration of vision in cases of advanced degeneration by the use of preserved inner retinal layers. The diversity of these approaches takes account of the broad spectrum of diseases that ranges from a disease limited to the macula to a generalized rod-cone dystrophy and perspectively opens up individualized treatment strategies depending on the genotype and phenotype.},
}