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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

@article {pmid42637174,
year = {2026},
author = {Falcão, AS and Lopes-da-Silva, M and Antas, P and Escrevente, C and Pedro, M and Felgueiras, B and Caires, B and Coelho, R and Ferreira, IS and Santos, IP and Ciossek, T and Nicklin, P and Tenreiro, S and Seabra, MC},
title = {Enhancing lysosome function via TFEB activation reduces lipofuscin-like granules in the retinal pigment epithelium.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111215},
doi = {10.1016/j.exer.2026.111215},
pmid = {42637174},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) is the most common blinding disease in the western world and is currently incurable. Although the exact causes of AMD are not clear, the primary origin of pathology appears to be the aged retinal pigment epithelium (RPE) exhibiting signs of lysosomal dysfunction and oxidative damage. RPE is responsible for the daily digestion of photoreceptor outer segments (POS), imposing a heavy continuous burden on the lysosomal network. A cellular model of RPE lysosomal dysfunction can be achieved by feeding RPE with a single pulse of POS, leading to the accumulation of autofluorescence granules (AFG), similar to lipofuscin in vivo. Here we show that synchronous phagocytosis of POS leads to early transient mTOR activation followed by inhibition in late phagosome maturation. One of its substrates, the transcription factor EB (TFEB) increases during phagosome maturation albeit mostly in its inactive phosphorylated form. We questioned whether modulation of the mTOR/TFEB axis could improve POS clearance and hence reduce AFG load. Treatment of POS-fed cells after the appearance of AFGs with rapamycin, an mTORC1 inhibitor results in ∼30% reduction of AFG load. This effect is dependent on active lysosomal enzymes and induction of active dephosphorylated TFEB with consequent activation of GADD34 and lysosomal biogenesis. As a proof of concept, we show that overexpressing a constitutively active form of unphosphorylated TFEB dramatically reduces POS-dependent AFG accumulation. Overall, this study suggests that viral or pharmacological approaches activating the TFEB pathway in the RPE could be beneficial as cell-protective treatment of early/intermediate cases of AMD, acting to delay progression of the disease.},
}

@article {pmid42639196,
year = {2026},
author = {Shehryar, T and Fazal, ZZ and Salam, AA and Varada, S and Jabran, F and Akram, MU},
title = {Why aren't we using AI in eye clinics? A systematic review of barriers and solutions in AI-based fundus image diagnostics for ocular diseases.},
journal = {International journal of ophthalmology},
volume = {19},
number = {9},
pages = {1809-1825},
pmid = {42639196},
issn = {2222-3959},
abstract = {Artificial intelligence (AI) has shown remarkable accuracy in the diagnosis of common ocular diseases such as diabetic retinopathy (DR), glaucoma, retinopathy of prematurity (ROP), and age-related macular degeneration (AMD), often matching or even outperforming expert clinicians. Despite these advancements, AI adoption in clinical settings remains limited due to key barriers. This systematic review evaluates 34 studies (2018-2025) highlighting AI's diagnostic performance (often >90% accuracy) while pointing out significant gaps in real-world deployment. We identify these persistent challenges through comprehensive analysis of current literature and propose actionable pathways to bridge the "last-mile gap" between research and clinical practice. This review pointed out three significant gaps in real-world deployment. These include 1) disjointed integration into clinical workflows, 2) lack of transparency in AI decision-making, and 3) poor generalizability across diverse populations. Our findings provide a framework for advancing AI implementation in ocular diagnostics to achieve equitable, scalable, and trustworthy solutions for global vision care.},
}

@article {pmid42639213,
year = {2026},
author = {Zhang, NY and Kong, HQ and Liao, YQ and Pan, YJ and Sun, W and Xi, L and Yu, HH and Shi, YH},
title = {Targeting ferroptosis in ocular diseases: mechanisms, clinical implications, and therapeutic horizons.},
journal = {International journal of ophthalmology},
volume = {19},
number = {9},
pages = {1858-1877},
pmid = {42639213},
issn = {2222-3959},
abstract = {Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has been increasingly implicated in selected ocular diseases, although its causal relevance varies across disease entities. The retina and retinal pigment epithelium are biologically susceptible to ferroptosis-related injury because of their high oxygen demand, abundant polyunsaturated lipids, mitochondrial activity, light exposure, and tightly regulated iron handling. This review summarizes core mechanisms of ocular ferroptosis, including iron uptake and export, glutathione-glutathione peroxidase 4 (GPX4)-dependent antioxidant defense, lipid peroxidation, mitochondrial dysfunction, neuroinflammation, and blood-retina barrier disruption. We discuss evidence from major degenerative, vascular, ischemic, hereditary, infectious, and immune-mediated retinal diseases, with particular attention to glaucoma, age-related macular degeneration, diabetic retinopathy, ocular toxoplasmosis, uveitis, retinal vasculitis, and inflammatory chorioretinopathy. We also evaluate ferroptosis-targeted therapeutic strategies, proposed operational criteria for defining ferroptosis in retinal disease, and candidate structural, functional, biochemical, and imaging endpoints for future translational studies. Current evidence supports ferroptosis as a context-dependent contributor to retinal injury rather than a uniform pathogenic mechanism. Future studies should integrate cell-type-resolved biomarkers, lipidomic and imaging readouts, functional rescue experiments, and clinically meaningful visual outcomes to clarify when ferroptosis modulation may support vision preservation.},
}

@article {pmid42639827,
year = {2026},
author = {Neumeister, N and Auer, EA and Patnaik, JL and Palestine, AG and Lynch, AM},
title = {Chronic Hypertension and Conversion from Intermediate Age-Related Macular Degeneration (iAMD) to the Advanced Phenotypes.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-4},
doi = {10.1080/09286586.2026.2719736},
pmid = {42639827},
issn = {1744-5086},
abstract = {PURPOSE: To assess the relationship between chronic hypertension (cHTN) and progression from intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) and neovascular AMD (NVAMD).

METHODS: We examined the records of iAMD patients recruited to the University of Colorado AMD Registry (July 2014 - June 2024). cHTN was self-reported at enrollment and confirmed by review of the Electronic Health Record (EHR). Number of prescribed antihypertensive medication classes was also collected. Conversion to GA and NVAMD was assessed through November 2024 with multi-modal imaging for each eye. Cox proportional hazards models with sandwich estimators were used to assess time to conversion.

RESULTS: We studied 900 eyes from 450 iAMD patients, of which 115 eyes (12.8%) converted to GA and 74 eyes (8.2%) converted to NVAMD. Neither measure of hypertension was associated with conversion to GA. In univariate analysis, patients with cHTN were at a 1.81 (95% CI: 1.06, 3.06, p = 0.029) times greater risk of conversion to NVAMD and were at a 1.30 (95% CI: 1.05, 1.62, p = 0.019) times greater risk of conversion to NVAMD for each additional antihypertensive medication class prescribed. In a body mass index (BMI) stratified analysis, the two measures of cHTN were associated with an elevated risk of conversion among overweight/obese patients (BMI ≥ 25 kg/m[2]) but not underweight/healthy patients (BMI < 25 kg/m[2]).

CONCLUSIONS: cHTN and antihypertensive medication class count were associated with conversion to NVAMD. BMI may be an effect modifier in the relationship between cHTN and progression from iAMD to NVAMD.},
}

@article {pmid42640154,
year = {2026},
author = {Wang, J and Osada, H and Chen, S and Yamaguchi, S and Hayashi, K and Negishi, K and Kurihara, T and Ban, N},
title = {Nicotinamide Mononucleotide Attenuates Inflammatory Activation, Choroidal Neovascularization, and Lesion-Associated Remodeling.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {59},
doi = {10.1167/iovs.67.10.59},
pmid = {42640154},
issn = {1552-5783},
mesh = {Animals ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; Mice ; Mice, Inbred C57BL ; Disease Models, Animal ; Blotting, Western ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; Choroid/pathology/metabolism/drug effects ; *Inflammation/drug therapy/metabolism ; Male ; Humans ; NF-kappa B/metabolism ; Cells, Cultured ; },
abstract = {PURPOSE: To evaluate the therapeutic potential of nicotinamide mononucleotide (NMN) for modulating the neurovascular inflammatory microenvironment and blunting tissue remodeling in neovascular age-related macular degeneration (nAMD).

METHODS: A laser-induced choroidal neovascularization (CNV) model was established in C57BL/6J mice, and CNV lesion size was quantified on RPE/choroid flat mounts. Immunostaining evaluated myeloid cell accumulation and fibrosis-associated remodeling. Quantitative RT-PCR and Western blotting assessed inflammatory/angiogenic gene expression and signaling activation in the retina and RPE/choroid. In vitro, lipopolysaccharide (LPS)-stimulated bEnd.3 and primary mouse RPE cells and TGF-β-stimulated THP-1-derived macrophage cells were used to model inflammatory and profibrotic responses.

RESULTS: NMN treatment significantly reduced CNV size in the laser-induced CNV model. This was accompanied by decreased myeloid cell accumulation within CNV lesions. NMN attenuated inflammatory and angiogenesis-related gene expression in the RPE/choroid and neural retina and reduced downstream signaling activation. In vitro, NMN suppressed LPS-induced inflammatory and proangiogenic responses in primary RPE cells and bEnd.3 endothelial cells and inhibited NF-κB activation. NMN further attenuated tissue remodeling, as shown by reduced collagen I-positive area under prolonged and delayed dosing regimens, together with decreased F4/80-positive area and α-smooth muscle actin-positive area within CNV lesions. In TGF-β-induced THP-1-derived macrophage cells, NMN suppressed profibrotic responses.

CONCLUSIONS: Our findings indicate that NMN reduces inflammatory signaling and alleviates the inflammatory microenvironment in CNV, accompanied by decreased angiogenesis-related gene expression and fibrosis-related remodeling. By attenuating inflammatory activation and tissue remodeling processes, NMN warrants further evaluation as an adjunctive approach to limit CNV progression and late-stage tissue remodeling in nAMD.},
}

Animals
*Choroidal Neovascularization/drug therapy/pathology/metabolism
Mice
Mice, Inbred C57BL
Disease Models, Animal
Blotting, Western
Retinal Pigment Epithelium/drug effects/metabolism/pathology
Choroid/pathology/metabolism/drug effects
*Inflammation/drug therapy/metabolism
Male
Humans
NF-kappa B/metabolism
Cells, Cultured

@article {pmid42640156,
year = {2026},
author = {Cicinelli, MV and Bianco, L and Antropoli, A and Bandello, F and Borrelli, E and Edwards, M},
title = {From Subretinal to Intraretinal Fluid in Type 1 Macular Neovascularization: A Clinicopathologic Disease Transition Model.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {57},
doi = {10.1167/iovs.67.10.57},
pmid = {42640156},
issn = {1552-5783},
mesh = {Humans ; *Subretinal Fluid/metabolism/diagnostic imaging ; Female ; Tomography, Optical Coherence/methods ; Male ; Retrospective Studies ; Visual Acuity/physiology ; Aged ; Aquaporin 4/metabolism ; *Retinal Neovascularization ; Fluorescein Angiography ; Aged, 80 and over ; *Wet Macular Degeneration/metabolism/diagnosis ; Immunohistochemistry ; Glial Fibrillary Acidic Protein/metabolism ; Follow-Up Studies ; Disease Progression ; },
abstract = {PURPOSE: To characterize the transition from subretinal fluid (SRF)-dominant to intraretinal fluid (IRF)-dominant exudation in type 1 macular neovascularization (MNV) secondary to neovascular age-related macular degeneration (nAMD), using longitudinal optical coherence tomography (OCT) phenotyping and exploratory clinicopathologic correlation.

METHODS: Serial OCT volumes from eyes with type 1 MNV and baseline SRF without IRF were retrospectively reviewed to define the temporal sequence of subretinal hyperreflective material (SHRM) formation, external limiting membrane (ELM) disruption and descent, IRF emergence, and outer retinal remodeling. Time-dependent Cox regression identified predictors of IRF development, and linear mixed-effects models related structural transitions to visual acuity (VA). Exploratory immunohistochemistry for glial fibrillary acidic protein and aquaporin-4 (AQP4) was performed in a donor eye with nAMD.

RESULTS: Among 143 eyes (130 patients; median follow-up, 49.2 months [interquartile range, 28.2-90.8]), SHRM developed in 85 eyes (59%), ELM disruption or descent in 67 eyes (47%), and IRF in 44 eyes (31%). ELM alterations preceded IRF occurrence in 74% of eyes (hazard ratio, 12.94; 95% CI, 6.41-26.11). IRF onset was associated with worse VA (β = +0.07 logMAR; P < 0.001) and accelerated visual decline (time × IRF interaction: β = +0.019 logMAR/year; P = 0.004). Histopathology demonstrated Müller cell extension beyond the ELM into fibrovascular tissue, reactive gliosis, and AQP4 redistribution, mirroring ELM descents and outer retinal adhesions observed on OCT.

CONCLUSIONS: In type 1 MNV, the shift to IRF-dominant exudation may reflect a structural disease state transition in which ELM disruption, Müller cell remodeling, and altered AQP4-mediated fluid transport are contributing mechanisms. These findings provide a possible clinicopathologic framework for developing outer retina-preserving therapeutic strategies in nAMD.},
}

Humans
*Subretinal Fluid/metabolism/diagnostic imaging
Female
Tomography, Optical Coherence/methods
Male
Retrospective Studies
Visual Acuity/physiology
Aged
Aquaporin 4/metabolism
*Retinal Neovascularization
Fluorescein Angiography
Aged, 80 and over
*Wet Macular Degeneration/metabolism/diagnosis
Immunohistochemistry
Glial Fibrillary Acidic Protein/metabolism
Follow-Up Studies
Disease Progression

@article {pmid42640395,
year = {2026},
author = {Lin, L and Zhang, J and Xie, X},
title = {Exosomes in the treatment of age-related ophthalmic diseases: an updated review.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42640395},
issn = {1573-2630},
support = {XKTD2022005//Chengdu University of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Exosomes/physiology ; *Macular Degeneration/therapy ; *Dry Eye Syndromes/therapy ; *Drug Delivery Systems/methods ; *Cataract/therapy ; *Aging ; },
abstract = {Exosomes are nanoscale extracellular vesicles of endosomal origin that mediate intercellular communication by transferring bioactive cargo, including proteins, lipids, messenger RNAs, microRNAs, and other regulatory molecules. Through this process, they can modulate the biological functions of recipient cells. Age-related ophthalmic diseases, including age-related macular degeneration (AMD), dry eye disease (DED), and age-related cataract (ARC), are degenerative ocular conditions whose incidence increases with age and are associated with chronic inflammation, oxidative stress, dysregulated angiogenesis, tissue fibrosis, epithelial injury, and apoptosis. Diabetic retinopathy (DR), although not classically defined as an age-related ophthalmic disease, is also briefly discussed in this review as an age-associated metabolic retinal comorbidity. Existing clinical treatments have several limitations, including the need for repeated administration, variable therapeutic responses, and potential adverse effects. Because of their biocompatibility, low immunogenicity, modifiable cargo and potential for local delivery, exosomes are being investigated as therapeutic agents and drug delivery vehicles in ophthalmology. This review summarizes the biological characteristics of exosomes and their potential relevance to ophthalmic applications, reviews recent evidence on their roles and mechanisms in major age-related ophthalmic diseases, and discusses the current limitations and future directions of exosome-based therapeutic strategies.},
}

Humans
*Exosomes/physiology
*Macular Degeneration/therapy
*Dry Eye Syndromes/therapy
*Drug Delivery Systems/methods
*Cataract/therapy
*Aging

@article {pmid42640457,
year = {2026},
author = {Marechal, V and Amoroso, F and Pacurariu, S and Capuano, V and Mehanna, CJ and Miere, A and Xompero, C and Semoun, O and Souied, EH},
title = {Real-world outcomes after switching to faricimab in treatment-resistant neovascular AMD: Short-term response and 12-month follow-up.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261478167},
doi = {10.1177/11206721261478167},
pmid = {42640457},
issn = {1724-6016},
abstract = {AimsTo assess the efficacy and safety of faricimab in neovascular age-related macular degeneration (nAMD) resistant to anti-VEGF therapies.MethodsThis retrospective study evaluated nAMD patients with persistent fluid despite anti-VEGF treatments (aflibercept or ranibizumab; mean injection interval of 4.63 ± 0.78 weeks), switched to faricimab and treated with three monthly injections. Data included demographics, baseline macular characteristics and prior treatments. Outcomes focused on anatomical changes (central macular thickness (CMT), pigment epithelial detachment (PED) height, fluid resolution), predictive factors for response, and fluid-free intervals.ResultsSeventy-five eyes from 64 patients (mean age 81.5 years) with predominantly type 1 macular neovascularization (84%) and extensive prior anti-VEGF exposure (mean 43.7 injections) were analyzed. Complete dryness was achieved in 58.67% of cases, with partial dryness in 28%. CMT and PED height showed significant reductions (p < 0.0001), while visual acuity remained stable throughout follow-up. In a selected subgroup of complete responders with at least 12-month follow-up (42/75 eyes), CMT reduction was maintained, but these longer-term findings should be interpreted cautiously because of potential selection bias. In cases with complete fluid resolution, the fluid-free interval averaged six weeks.ConclusionFaricimab offers notable anatomical improvements in nAMD resistant to anti-VEGF therapy, with stable visual acuity. In this heavily pretreated, treatment-resistant population, treatment intervals nevertheless remained short, averaging less than six weeks (5.34 ± 1.31 weeks), so the main benefit appears anatomical, with limited evidence for functional gain or reduced treatment burden.},
}

@article {pmid42640660,
year = {2026},
author = {McLaughlin, SA and Bineshfar, N and Williams, BK},
title = {RE: Comment on: "Impact of GLP-1 Receptor Agonists for Type 2 Diabetes Mellitus on the Development and Progression of Age-Related Macular Degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004995},
pmid = {42640660},
issn = {1539-2864},
}

@article {pmid42624227,
year = {2026},
author = {Zhong, Y and Feng, M and Tawfeeq, RD and Cheng, J},
title = {Emerging Research Trends in the Application of Artificial Intelligence, LLMs, Machine Learning, and Deep Learning in Ophthalmic Diseases: A Bibliometric and Visual Analysis.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105628},
doi = {10.1016/j.pdpdt.2026.105628},
pmid = {42624227},
issn = {1873-1597},
abstract = {BACKGROUND: To examine global research activity in the application of artificial intelligence, large language models, machine learning, and deep learning in ophthalmic diseases from 2015 to 2025.

METHODS: The study retrieved relevant publications from the Web of Science Core Collection. Bibliometric indicators were analysed using VOSviewer, CiteSpace, and Bibliometrix. Annual publication numbers, citation distribution, countries, institutions, journals, co-cited journals, author productivity, co-authorship networks, keyword frequency, burst terms, and thematic clusters were assessed.

RESULTS: A total of 1,997 articles were included in this analysis based on the inclusion criteria. Annual publication numbers increased after 2018 and remained high from 2020 to 2025. The United States, China, and the United Kingdom showed the highest research output.The University of California System, the University of London and University College London were leading institutions in terms of publication output. The most common keywords included deep learning, optical coherence tomography, diabetic retinopathy, and macular degeneration. Citation burst analysis identified influential articles on diabetic retinopathy detection, optical coherence tomography biomarker analysis, and residual network models. Visual cluster analysis identified themes related to automated retinal imaging, diabetic retinopathy screening, fluid quantification models, multimodal image analysis, and recent studies using large language models.

CONCLUSION: Artificial intelligence and deep learning research in ophthalmology has increased significantly, with imaging-based studies contributing the highest output. Publications on LLM-based applications have also increased during recent years. This bibliometric analysis summarizes the distribution of publications, research themes, and methodological trends in ophthalmic artificial intelligence and provides a basis for future clinical and research applications.},
}

@article {pmid42624312,
year = {2026},
author = {de Carlo Forest, TE and Mathias, MT and Grove, N and Manoharan, N and Cordaro, N and Beckwith, AD and Nebbia, G and McNamara, SM and Kalpathy-Cramer, J and Lynch, AM and Mandava, N},
title = {Describing Candidate Geographic Atrophy Phenotypes and Their Different Growth Parameters.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.023},
pmid = {42624312},
issn = {1879-1891},
abstract = {PURPOSE: Describe distinct candidate geographic atrophy (GA) phenotypes in age-related macular degeneration (AMD) and their different growth parameters.

DESIGN: Prospective cohort study.

METHOD: Patients with GA enrolled in the University of Colorado AMD Registry from 9/2014-9/2022, with follow-up through 4/2023 were included. Patients with ≥five fundus autofluorescence (FAF) time points were included. Longitudinal FAFs for each patient's eye were reviewed by two graders for candidate GA phenotype: (1) unifocal foveal-involving, (2) large coalescing multifocal, (3) small numerous multifocal, as well as presence of a concomitant peripapillary component. Each FAF image was processed using an artificial intelligence (AI) based segmentation model to automatically delineate GA lesions and calculate lesion area, with manual review and adjustment performed by a vitreoretinal specialist. Square-root transformed (SQRT) growth rate was calculated per eye. Gompertz modelling of GA growth was performed to estimate each eye's maximum GA growth rate and maximum projected GA size. Linear regression using generalized estimating equations was used to estimate associations between phenotypes and measures of GA growth rate.

RESULTS: 81 eyes with GA from 48 patients were included. Average subject age was 80 years (SD: 8). Average baseline GA size was 6.4 mm[2] (SD:7.5). Eyes with a peripapillary component had faster modeled maximum GA growth rates (Beta 0.37; 95%CI:0.16,0.59; p<0.001) and higher predicted maximum GA size (Beta 0.24; 95%CI:0.10,0.38; p<0.001) in univariate analysis. After adjusting for presence of a peripapillary component, the large coalescing multifocal and small numerous multifocal phenotypes had larger predicted maximum GA sizes than the unifocal foveal-involving phenotype (Beta 0.10; 95%CI:0.03,0.18; p=0.009 and Beta 0.10; 95%CI:-0.00,0.21; p=0.059, respectively). The small numerous multifocal phenotype had faster SQRT and modeled maximum GA growth rates compared to the unifocal foveal-involving phenotype (Beta 0.09; 95%CI:0.03,0.16; p=0.005 and Beta 0.29; 95%CI:0.13,0.44; p<0.001, respectively), and the large coalescing multifocal phenotype had borderline faster SQRT growth rates than the unifocal foveal-involving phenotype (p=0.05). Further, the small numerous multifocal phenotype had marginally higher modeled maximum GA growth rates than the large coalescing multifocal phenotype (estimated marginal mean difference 0.200mm/yr; 95%CI:-0.00,0.40; p=0.054).

CONCLUSION: We describe three candidate GA phenotypes and their different growth parameters. The large coalescing multifocal and small numerous multifocal phenotypes had more severe growth trajectories, and presence of a peripapillary component portended more severe outcomes. This may have implications for clinical trial interpretation and clinical prognostication.},
}

@article {pmid42626053,
year = {2026},
author = {Zeppieri, M and Capobianco, M and Visalli, F and Khouyyi, M and Musa, M and Avitabile, A and Leandro, I and Giglio, R and Tognetto, D and Gagliano, C and D'Esposito, F and Cappellani, F},
title = {Artificial intelligence in ophthalmology: From diagnostic accuracy to clinical application.},
journal = {World journal of methodology},
volume = {16},
number = {3},
pages = {115265},
pmid = {42626053},
issn = {2222-0682},
abstract = {Artificial intelligence in ophthalmology encounters a continual challenge: Systems proficient in picture classification seldom yield quantifiable enhancements in patient outcomes. The primary concern is the disparity between pixel-level performance metrics and their clinical significance. Primary obstacles encompass data bias, domain shift, and label noise, exacerbated by the lack of prospective, randomized deployment trials. The frequent disregard for patient-centered objectives, cost-effectiveness, and equity evaluations is significant. Rectifying these deficiencies necessitates stringent external validation, established decision criteria, and ongoing surveillance within actual clinical practices. Transparent reporting criteria and the deliberate incorporation of human-factors engineering are essential. Only by bridging this gap can algorithmic accuracy be converted into significant diagnostic precision for glaucoma, diabetic retinopathy, and macular conditions (specifically diabetic macular edema and age-related macular degeneration). This paper aims to assess the limits of using high-performing artificial intelligence systems in ocular image processing, which seldom lead to enhanced patient outcomes, and to delineate the scientific, clinical, and practical techniques required to close this gap.},
}

@article {pmid42626541,
year = {2026},
author = {Xin, X and Zhao, X and Ling, F and Qin, L and Liu, X and Liu, C},
title = {CircMETTL3 Inhibits H2O2-Induced Senescence, Oxidative Stress, and DNA Damage in ARPE-19 Cells via miR-100/BMPR2 Axis.},
journal = {Journal of ophthalmology},
volume = {2026},
number = {},
pages = {3194421},
pmid = {42626541},
issn = {2090-004X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a common degenerative eye disease that eventually leads to irreversible vision loss. CircRNAs have received increasing attention for their regulatory role in AMD. In this study, whole transcriptome sequencing identified differentially expressed circRNA (circMETTL3) in AMD. Previous studies have unlocked the potential mechanism of circMETTL3 in cancer, but its role in AMD has not been studied.

METHODS: ARPE-19 cells treated with H2O2 were used as the AMD cell model. The senescence, oxidative stress, and DNA damage of ARPE-19 cells were determined by SA-β-gal staining, DCFH-DA staining, and IF assay. The levels of RPE-specific markers or mRNA levels were assessed using western blot assay. The potential mechanism of circMETTL3 was investigated by luciferase reporting assay and RIP assay.

RESULTS: CircMETTL3 was revealed to decrease in AMD cell models. The addition of circMETTL3 decreased SA-β-gal staining and ROS production and facilitated cell viability in H2O2-treated ARPE-19 cells. Moreover, γH2AX and KRT18 levels were suppressed, and TJP1, BEST1, and CTNNB1 protein levels were increased by circMETTL3 addition. In addition, circMETTL3 could bind to and negatively regulate miR-100. Overexpression of miR-100 exacerbated senescence, oxidative stress, and DNA damage in H2O2-treated ARPE-19 cells, which reversed the effects of circMETTL3. Furthermore, BMPR2 was targeted by miR-100. Overexpression of BMPR2 inhibited H2O2-induced cell damage in ARPE-19 cells, which reversed the effects of miR-100.

CONCLUSIONS: In sum, these findings demonstrated that the circMETTL3/miR-100/BMPR2 axis plays a vital regulatory role in AMD development.},
}

@article {pmid42627194,
year = {2026},
author = {Pitsillidou, O and Petrou, P and Postma, MJ},
title = {Cost-neutral adoption of anti-VEGF therapies in neovascular age-related macular degeneration.},
journal = {Expert review of pharmacoeconomics & outcomes research},
volume = {},
number = {},
pages = {1-6},
doi = {10.1080/14737167.2026.2717293},
pmid = {42627194},
issn = {1744-8379},
abstract = {OBJECTIVE: In therapeutic classes characterized by outcome equivalence, the decision problem shifts from incremental cost-effectiveness to cost-neutral pricing. This study formalizes a break-even pricing framework, translating real-world utilization and costs into cost-neutral price thresholds, using anti-VEGF therapies for neovascular age-related macular degeneration (nAMD) as a case study.

METHODS: A cost-minimization framework was applied from a public payer perspective in a single-payer system (Cyprus). Five anti-VEGF agents were evaluated over 3 years with 3.5% discounting. Injection frequencies were derived as weighted averages of treat-and-extend and pro re nata regimens from Phase 3/4 trials, with year 3 extrapolated from year 2. Break-even prices were defined as unit prices yielding equal discounted per-patient costs versus comparators. First-line thresholds used bevacizumab; second-line thresholds used a utilization-weighted comparator. Sensitivity analyses were conducted.

RESULTS: Bevacizumab defined the lowest-cost benchmark (€4,130). Cost-neutral first-line use of newer agents required price reductions of 84-98%. Under second-line utilization, several agents fell below break-even thresholds at list prices. Key drivers were acquisition price, injection frequency, and monitoring costs.

CONCLUSION: Break-even pricing generates explicit cost-neutral thresholds under outcome equivalence. While jurisdiction-specific, the framework is transferable and supports consistent pricing decisions in single-payer systems.},
}

@article {pmid42627258,
year = {2026},
author = {Iglicki, M and Zur, D and Melamud, JI and Loewenstein, A},
title = {Biomarker-Guided Management in Vitreoretinal Diseases: Integrating Imaging, Pharmacotherapy, and Surgical Decision-Making-A Narrative Review.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004984},
pmid = {42627258},
issn = {1539-2864},
abstract = {PURPOSE: To synthesize current evidence on imaging biomarkers in vitreoretinal diseases and to review the potential for a biomarker-guided framework integrating imaging, pharmacotherapy, and surgical decision-making in contemporary clinical practice.

METHODS: This narrative review integrates published evidence and clinical insights on optical coherence tomography (OCT) and OCT angiography (OCTA)-derived biomarkers, focusing on their role in predicting disease behavior, therapeutic response, and surgical indications.

RESULTS: Key imaging biomarkers-including disorganization of the retinal inner layers (DRIL), hyperreflective foci (HRF), intraretinal and subretinal fluid patterns, and vascular perfusion changes-demonstrate significant value in stratifying disease phenotype and guiding management. Biomarker-based approaches enable differentiation between angiogenic and inflammatory patterns, supporting individualized therapeutic strategies. These include optimized use of anti-vascular endothelial growth factor therapy, corticosteroid-based treatments, and newer long-acting agents. In addition, imaging biomarkers play a central role in identifying surgical candidates and determining timing of intervention, particularly in tractional maculopathies and refractory disease.

CONCLUSION: A biomarker-guided approach provides a clinically actionable framework for personalized vitreoretinal care. The integration of multimodal imaging with pharmacologic and surgical decision-making represents a critical step toward precision medicine, with the potential to improve outcomes and reduce treatment burden.},
}

@article {pmid42623949,
year = {2026},
author = {Xie, Y and He, P and Lv, J and Li, X and Zhou, X and Li, Z and Jiang, X and Zhang, L and Yu, Y and Chen, F},
title = {Antioxidant hydrogel eye drops for the effective management of dry age-related macular degeneration by enhancing SIRT1/Nrf2 signaling.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {161},
number = {},
pages = {158709},
doi = {10.1016/j.phymed.2026.158709},
pmid = {42623949},
issn = {1618-095X},
abstract = {BACKGROUND: Dry age-related macular degeneration (dAMD) is a major cause of irreversible vision loss, in which oxidative stress-induced retinal pigment epithelial injury plays a key role. Astragaloside IV (ASIV) has antioxidant potential but is limited by poor aqueous solubility and ocular bioavailability.

PURPOSE: To evaluate the retinal protective effects of an ASIV-loaded antioxidant hydrogel eye drop (ALG) in experimental dAMD.

METHODS: A NaIO₃-induced mouse model of dAMD was established. Retinal protection was evaluated using hematoxylin and eosin (H&E) staining, immunofluorescence, ophthalmic imaging, and functional examinations. Cytocompatibility and cellular uptake were assessed in ARPE-19 cells.

RESULTS: ALG underwent a sol-gel transition at 35 °C and displayed a markedly sustained release profile compared with free ASIV. In vivo, ALG reduced retinal ROS accumulation and increased retinal sirtuin 1 (SIRT1) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression. In addition, ALG exhibited favorable cytocompatibility. Compared with liposomes and eye drops, the liposome gel also showed greater uptake by ARPE-19 cells.

CONCLUSION: ALG attenuated oxidative stress-related retinal injury, and meanwhile retinal SIRT1 and Nrf2 expression increased. Therefore, ALG may exert therapeutic effects against dAMD in association with SIRT1/Nrf2 upregulation.},
}

@article {pmid42622344,
year = {2026},
author = {Pandala, N and Haefeli, LM and Lang, M and Stone, EM and Mullins, RF and Tucker, BA and Han, IC},
title = {Development of a Targeted Choroidal Injury Model for the Study of Retinal Degenerations and Therapeutic Cell Replacement.},
journal = {Translational vision science & technology},
volume = {15},
number = {8},
pages = {17},
doi = {10.1167/tvst.15.8.17},
pmid = {42622344},
issn = {2164-2591},
mesh = {Animals ; Rats, Sprague-Dawley ; *Disease Models, Animal ; *Choroid/injuries/pathology/drug effects ; Rats ; *Retinal Degeneration/pathology/therapy ; Iodates/toxicity ; Male ; Immunohistochemistry ; },
abstract = {PURPOSE: Loss of the choroid is an important pathophysiological step in retinal diseases ranging from age-related macular degeneration (AMD) to choroideremia. However, current models of choroidal injury, such as laser photocoagulation-induced injury, induce acute tissue damage that does not parallel the gradual loss seen in most retinal degenerations. As such, there remains a need for models of targeted choroidal injury to study mechanisms of disease and develop potential treatments.

METHODS: We report a targeted choroidal injury model using bioconjugated saporins (immunotoxins) against cluster of differentiation (CD) domains CD38 and CD105. To induce injury, 10 µL of bioconjugate solution or control (phosphate-buffered saline) was delivered via suprachoroidal injection in wild-type Sprague-Dawley (SD) and Sprague-Dawley Rag2/Il2rg (SRG; double-knockout) rats. The extent and severity of choroidal injury were compared with animals treated with sodium iodate administered via tail vein injections at 1, 2, and 3 weeks post-treatment using clinical imaging and immunohistochemistry.

RESULTS: Choroidal injury induced by either anti-CD38 or anti-CD105 immunotoxin was targeted to the choroid and localized to the sector of the injection, unlike global destruction induced by sodium iodate. Immunotoxin-induced vascular damage remained constant over 3 weeks, without choroidal neovascularization seen, whereas sodium iodate caused progressive and severe injury of the choroid and overlying retina.

CONCLUSIONS: Suprachoroidal injection of anti-CD38 and anti-CD105 immunotoxins can induce localized and durable choroidal injury in both wild-type and immunosuppressed rats.

TRANSLATIONAL RELEVANCE: Immunotoxin-based models of targeted choroidal injury may be useful for understanding pathophysiologic mechanisms and developing therapies in conditions involving choroidal cell death.},
}

Animals
Rats, Sprague-Dawley
*Disease Models, Animal
*Choroid/injuries/pathology/drug effects
Rats
*Retinal Degeneration/pathology/therapy
Iodates/toxicity
Male
Immunohistochemistry

@article {pmid42622722,
year = {2026},
author = {Katabami, T and Ota, M and Saeki, Y and Yashiro, K and Aoki, S and Kitamoto, K and Terao, R and Azuma, K},
title = {Faricimab for treatment-naïve nAMD: 1- and 2-year outcomes and PS-OCT polarimetric entropy.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42622722},
issn = {1573-2630},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; *Visual Acuity ; Intravitreal Injections ; Female ; Male ; Aged ; Follow-Up Studies ; Time Factors ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Treatment Outcome ; Angiogenesis Inhibitors/administration & dosage ; Fluorescein Angiography/methods ; Fundus Oculi ; Entropy ; Antibodies, Bispecific ; },
abstract = {BACKGROUND: To evaluate 1- and 2-year real-world outcomes of intravitreal faricimab for treatment-naïve neovascular age-related macular degeneration (nAMD) and to explore factors associated with visual acuity change, including polarization-sensitive OCT (PS-OCT)-derived polarimetric entropy (PE).

METHODS: This retrospective single-center study included 27 treatment-naïve nAMD eyes initiating faricimab; all eyes were evaluable at 1 year (n = 27) and 18 at 2 years (n = 18). BCVA (logMAR), central retinal thickness (CRT), PE, and entropy-defined HRF-like foci (HEF)-related metrics were assessed. Associations with ΔlogMAR (post-pre) were examined using multivariable linear regression. Prespecified baseline-BCVA-adjusted and EZ-adjusted sensitivity models were additionally performed. EZ integrity was graded at the fovea and included in sensitivity analyses.

RESULTS: BCVA improved from 0.40 ± 0.28 to 0.20 ± 0.23 at 1 year (P < 0.0001). In the 2-year cohort, BCVA improved from 0.35 ± 0.28 to 0.15 ± 0.20 at 1 year (P = 0.0003) and 0.12 ± 0.17 at 2 years (P = 0.0004). CRT decreased from 337.5 ± 159.8 to 186.7 ± 47.3 µm at 1 year (P < 0.0001) and from 337.3 ± 185.9 to 185.1 ± 46.4 µm at 1 year (P = 0.0019) and 181.2 ± 60.9 µm at 2 years (P < 0.0001). Mean PE increased at 1 year (0.44 ± 0.06 to 0.46 ± 0.05; P < 0.0001) but not from baseline to 2 years (P = 0.81). In multivariable analyses, ΔPE was associated with 1-year ΔlogMAR (β; - 2.7 to - 2.8; P ≤ 0.01) together with MNV subtype, whereas at 2 years the incremental association of ΔPE was attenuated in baseline-adjusted and EZ-adjusted sensitivity analyses in the 2-year completer cohort.

CONCLUSIONS: Faricimab treatment was associated with sustained functional and anatomical improvement in treatment-naïve nAMD. PE change may serve as a complementary imaging marker associated with visual improvement, particularly at 1 year, while longer-term associations warrant confirmation in larger cohorts.},
}

Humans
*Tomography, Optical Coherence/methods
Retrospective Studies
*Visual Acuity
Intravitreal Injections
Female
Male
Aged
Follow-Up Studies
Time Factors
*Wet Macular Degeneration/drug therapy/diagnosis/physiopathology
Treatment Outcome
Angiogenesis Inhibitors/administration & dosage
Fluorescein Angiography/methods
Fundus Oculi
Entropy
Antibodies, Bispecific

@article {pmid42623367,
year = {2026},
author = {Do Song, Y and Kim, J and Jang, JH and Kim, Y and Oh, HK and Ji, MJ and Choi, M and Park, M and Kim, DW},
title = {Generation of dual mouse models of retinal degeneration with slow and rapid progression driven by ectopic RIP3 expression.},
journal = {PloS one},
volume = {21},
number = {8},
pages = {e0356284},
pmid = {42623367},
issn = {1932-6203},
mesh = {Animals ; *Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism ; Mice, Transgenic ; *Disease Models, Animal ; Mice ; *Retinal Degeneration/pathology/genetics/metabolism ; Disease Progression ; Retinal Pigment Epithelium/pathology/metabolism ; Humans ; },
abstract = {Dry age-related macular degeneration (AMD) is a leading cause of blindness, characterized by progressive loss of retinal pigment epithelium (RPE) and subsequent photoreceptor degeneration. Current experimental models, including sodium iodate-induced injury, fail to fully recapitulate the chronic, age-related progression of the human disease. Although RIP3-mediated necroptosis has been strongly implicated in RPE cell death, its direct contribution to retinal degeneration in vivo remains unclear. To address this limitation, we generated two RIP3 transgenic mouse lines with distinct patterns of RIP3 overexpression. While RIP3-Tg mice exhibit systemic RIP3 overexpression, RIP3-Tg-RPE mice display additional RPE-specific overexpression beyond the levels observed in RIP3-Tg mice. We then evaluated these transgenic lines, along with wild-type controls, for age-driven retinal degeneration by using optical coherence tomography (OCT), behavior-based visual function assays, and molecular profiling of inflammation and cell death. First, RIP3-Tg mice exhibited gradual retinal thinning, progressive visual decline, and sustained upregulation of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) over 6-15 months, recapitulating the slow progression of dry-AMD. Second, RIP3-Tg-RPE mice, which exhibit further RPE-specific increases in RIP3 expression, showed markedly accelerated retinal degeneration, with significant structural and functional deficits evident as early as 2 months of age. These findings indicate that ectopic RIP3 expression in the RPE contributes to inflammatory responses and subsequent retinal degeneration. Collectively, our results highlight RIP3 as a potential contributing factor in the progression of retinal degeneration and introduce biologically relevant transgenic models that capture both slow and accelerated disease progression. These models provide a valuable platform for investigating disease mechanisms and developing therapeutic strategies targeting necroptosis in dry-AMD.},
}

Animals
*Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism
Mice, Transgenic
*Disease Models, Animal
Mice
*Retinal Degeneration/pathology/genetics/metabolism
Disease Progression
Retinal Pigment Epithelium/pathology/metabolism
Humans

@article {pmid42623818,
year = {2026},
author = {Dai, J and Zhou, X and Zeng, M and Sun, Z and Luo, W and He, Y and Peng, Q and Wu, Q},
title = {Standard Tea Intake Is Causally Associated with a Reduced Risk of Wet Age-Related Macular Degeneration: A Mendelian Randomization Study.},
journal = {Physiological genomics},
volume = {},
number = {},
pages = {},
doi = {10.1152/physiolgenomics.00314.2025},
pmid = {42623818},
issn = {1531-2267},
support = {2023JJ40474//Youth Science Fund of Hunan Science Foundation/ ; 82004427//National Natural Science Foundation of China/ ; 2017TP1018//Key Laboratory of TCM Prevention and Treatment of Eye,Ear, Nose and Throat Diseases of Hunan Province/ ; 2018TP2008//Hunan Provincial Engineering Technology Research Center for TCM Prevention and Treatment of Eye, Ear, Nose and Throat Diseases and Visual Function Protection/ ; 2023SK4038//Hunan Clinical Medical Research Center of Ophthamology (TCM), China/ ; },
abstract = {Researchers have posited that increased consumption of tea and coffee may be associated with more favourable treatment outcomes in patients with age-related macular degeneration (AMD). However, there is no clear evidence regarding the causal associations. To delve deeper into this potential connection, scientists employed a rigorous method known as Mendelian randomization (MR). This technique was utilized to explore the causal impact of tea and coffee consumption on the development or progression of AMD. With the aim of investigating the cause-effect relationship between 16 tea and coffee consuming subtypes and 3 AMD, we designed a two-sample MR-study using comprehensive data from genome-wide association studies (GWAS). The major approach adopted was inverse variance weighting (IVW). Furthermore, we implemented complementary methods like the weighted median (WM), weighted mode, and MR-Egger to strengthen our findings. Sensitivity analyses, including MR-Egger, MR-PRESSO, leave-one-out, and Cochran's Q tests, were employed to validate results, explore heterogeneity and pleiotropy, and pinpoint potential biases. 268 instrumental variables were selected for MR analysis. The results showed that standard tea intake may be a protective factor for wet AMD (OR=0.7076, 95%CI=(0.5776 - 0.8668), P=8×10-4, PFDR=0.0402). Sensitivity analysis suggests that the results are robust. Our findings provide genetic evidence that standard tea intake is a protective factor against wet AMD, providing new insights into early risk stratification and prevention strategies for the disease.},
}

@article {pmid42609323,
year = {2026},
author = {Singh Bhangu, J and Swarnkar, PK and Stewart, C and Rifat, M and Khalid, S and Al-Janabi, A and Awad, MH and Williams, GS},
title = {Faricimab versus Aflibercept for Discharge and Readmission in Neovascular Age-Related Macular Degeneration: A Lesion-Type Stratified, Real-World UK Analysis.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {593566},
pmid = {42609323},
issn = {1177-5467},
abstract = {BACKGROUND: Anti-VEGF treatment improves outcomes in neovascular age-related macular degeneration (nAMD) management. No real-world data have compared discharge and readmission rates between Faricimab and Aflibercept 2mg, stratified by lesion type.

METHODS: A retrospective audit study of 1004 eyes in 912 patients diagnosed with nAMD. Patients received either Faricimab or Aflibercept 2mg. The outcomes assessed were central macular thickness CMT, best-corrected visual acuity BCVA, fluid resolution, discharge to community care defined as being asymptomatic for more than 6 months and then reviewed by optometrist, and readmission. Lesion types were classified into Type 1, Type 2, and Prepapillary. Statistical analysis used t-tests, chi-square, and appropriate nonparametric tests.

RESULTS: The demographic of the patients in this study consisted of 60.6% of women with participants being on average 76.9 years old. Type 1 lesions had a greater change from baseline CMT, and a greater change in BCVA than Type 2 lesions. Discharge rates from hospital and the average time to discharge from hospital was greater for Faricimab (84.1%, 378 days) compared with Aflibercept (69.5%, 1048 days, p < 0.0001). The number of eyes readmitted was lower for Faricimab (14.7% vs 29.1%) and was not different for lesion type (p = 0.96). The number of injections was not different amongst discharged patients and readmitted patients. In this retrospective cohort, service outcomes at discharge and readmission appeared to differ between Faricimab and aflibercept, whereas no clear differences were observed by lesion type.

CONCLUSION: In this real-world audit, treatment with Faricimab was associated with higher discharge rates, earlier discharge, and fewer readmissions compared with aflibercept, although these findings should be interpreted as observational associations rather than causal effects. Lesion type did not appear to be an independent predictor of these service outcomes within the limits of this analysis.},
}

@article {pmid42610095,
year = {2026},
author = {Parmar, UPS and Singh, RB and Bhullar, S and Gupta, R and Gauba, A and Shayan, M and Rai, K and Ichhpujani, P},
title = {Nanotechnological Advances in Ocular Therapeutics: A Narrative Review of Drug Delivery Platforms, Clinical Applications, and Translational Challenges.},
journal = {Nanotechnology, science and applications},
volume = {19},
number = {},
pages = {611594},
pmid = {42610095},
issn = {1177-8903},
abstract = {PURPOSE: Nanotechnology-based ocular drug delivery systems offer a promising approach to overcoming the anatomical and physiological barriers that limit the efficacy of conventional ophthalmic formulations, where topical bioavailability typically remains below 5% owing to rapid nasolacrimal drainage, precorneal tear turnover, and corneal impermeability. This narrative review synthesises current evidence on nanocarrier design, delivery pathways, and disease-specific therapeutic applications, incorporating cross-platform comparison across six nanocarrier systems and explicit stratification of evidence by translational stage.

METHODS: A structured narrative review was conducted using OVID MEDLINE, Embase, Scopus, Web of Science, and PubMed from database inception to September 2025, supplemented by citation chaining and targeted Google Scholar searches. Data extraction focused on carrier architecture, drug-loading and release characteristics, delivery routes, mechanistic behaviour, therapeutic outcomes, and safety profiles. This review was conducted in accordance with the general principles for narrative reviews as described in the Scale for the Assessment of Narrative Review Articles (SANRA).

RESULTS: Key nanocarrier classes included liposomes, polymeric micelles, dendrimers, nanosuspensions, nanoemulsions, and chitosan- and protein-based nanoparticles. Compared with conventional formulations, these systems demonstrated improved corneal residence, enhanced mucoadhesion, increased transscleral diffusion, reduced dosing frequency, and sustained intraocular exposure. Clinically translated examples include cyclosporine A nanomicelle and nanoemulsion formulations, marketed as Cequa (0.09%), Restasis (0.05%), and Ikervis (0.1%), approved for dry eye disease, and a subconjunctival PLGA nanoparticle depot that achieved greater than 20% intraocular pressure reduction sustained over 90 days from a single injection in early clinical evaluation. Applications spanned anterior-segment disorders, including dry eye disease, conjunctivitis, infectious keratitis, ocular inflammation, and glaucoma, and posterior-segment diseases such as diabetic retinopathy, age-related macular degeneration, retinoblastoma, and retinopathy of prematurity.

CONCLUSION: Lipid-based and polymeric nanocarrier platforms are currently closest to clinical translation, with approved formulations and early-phase trial data supporting meaningful therapeutic advantages over conventional delivery. Realising the full potential of ocular nanomedicine will require addressing residual challenges in long-term ocular safety, manufacturing scalability, and regulatory compliance, particularly for posterior-segment applications, where non-invasive topical delivery remains largely at the preclinical stage.},
}

@article {pmid42611377,
year = {2026},
author = {Yoo, HS and Yu, P and Zhou, C and Hosseini, A and Granville, DJ and Matsubara, JA},
title = {Emerging roles of granzymes in neurodegeneration and neuroinflammation: mechanistic insights and therapeutic opportunities.},
journal = {Acta neuropathologica},
volume = {152},
number = {1},
pages = {},
pmid = {42611377},
issn = {1432-0533},
mesh = {Humans ; *Granzymes/metabolism ; Animals ; *Neurodegenerative Diseases/enzymology/metabolism/pathology ; *Neuroinflammatory Diseases/enzymology/metabolism/pathology ; },
abstract = {Neurodegenerative diseases are increasingly recognized as disorders shaped not only by intrinsic neuronal vulnerability, but also by chronic neuroinflammation mediated by maladaptive neuroimmune signaling. Granzymes, a family of serine proteases classically studied for their cytotoxic roles in anti-viral and anti-tumor immunity, are emerging as important mediators of central nervous system (CNS) pathology. In addition to their canonical intracellular functions, granzymes can act extracellularly to cleave the extracellular matrix (ECM), activate cell-surface receptors, disrupt epithelial barrier function, amplify inflammatory cascades, and alter glial and neuronal responses to injury. In this review, we synthesize current knowledge on the roles of Granzyme A (GzmA), Granzyme B (GzmB), Granzyme H (GzmH), and Granzyme K (GzmK) in neurodegeneration and neuroinflammation across diverse CNS disease and injury contexts, such as Alzheimer's disease (AD), multiple sclerosis (MS), stroke, spinal cord injury (SCI), and age-related macular degeneration (AMD). GzmB is the most extensively characterized, with evidence supporting both intracellular neurotoxicity and extracellular pathogenic functions mediated through protease-activated receptor signaling, ECM cleavage, outer blood-retina barrier disruption, angiogenesis, fibrosis, and chronic inflammation. GzmA is implicated in tau proteolysis and structural destabilization of neurons and astrocytes, while GzmK has emerged as a context-dependent regulator of neuroinflammation through PAR-1 activation, microglial modulation, and complement cascade activation. GzmH remains the least understood but may contribute to nerve injury through mechanisms that are only beginning to be defined. We also discuss endogenous and pharmacological granzyme inhibition, highlighting the therapeutic promise of selective extracellular granzyme targeting, particularly for GzmB, while emphasizing the current lack of selective inhibitors for GzmA, GzmK, and GzmH. Collectively, these findings position granzymes as underappreciated neuroimmune effectors and potential therapeutic targets in neurodegenerative diseases and CNS injury.},
}

Humans
*Granzymes/metabolism
Animals
*Neurodegenerative Diseases/enzymology/metabolism/pathology
*Neuroinflammatory Diseases/enzymology/metabolism/pathology

@article {pmid42612071,
year = {2026},
author = {Mai, J and Liu, T and Yao, Y},
title = {lncRNAs and miRNAs in Exosome-Mediated Macrophage Polarization: Implications for Age-Related Macular Degeneration.},
journal = {Journal of visualized experiments : JoVE},
volume = {},
number = {233},
pages = {},
doi = {10.3791/71424},
pmid = {42612071},
issn = {1940-087X},
mesh = {*Exosomes/genetics/metabolism/immunology ; *Macrophages/immunology/metabolism/cytology ; Humans ; *Macular Degeneration/genetics/pathology/immunology/metabolism ; *MicroRNAs/genetics/immunology ; *RNA, Long Noncoding/genetics/immunology/metabolism ; Animals ; },
abstract = {Age-related macular degeneration (AMD) is a progressive and multifactorial retinal disease that represents a leading cause of irreversible vision loss among the elderly. Increasing evidence suggests that exosomes, small extracellular vesicles that mediate intercellular communication, play a critical role in regulating immune and angiogenic signaling in the retina. These vesicles transport diverse molecular cargo, including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Recent studies highlight the importance of exosome-mediated ncRNA signaling in macrophage polarization, a key immunological process involved in AMD progression. Exosomal miRNAs and lncRNAs released from retinal pigment epithelium (RPE) cells, endothelial cells, and immune cells can regulate macrophage phenotypes and alter inflammatory and angiogenic pathways within the retina. Dysregulated ncRNAs, including miR-21, miR-23a, miR-150, and the lncRNA NEAT1, have been implicated in promoting macrophage-driven inflammation, lipid dysregulation, and pathological neovascularization. Through these mechanisms, exosomal ncRNAs contribute to the transition from early retinal stress and drusen formation to advanced forms of AMD characterized by geographic atrophy or choroidal neovascularization. In addition to their mechanistic role in disease progression, exosomal ncRNAs show promise as minimally invasive biomarkers for early diagnosis and monitoring of AMD. Their stability in biological fluids, such as plasma, aqueous humor, and vitreous fluid, suggests their potential use in liquid biopsy approaches. Moreover, engineered exosomes carrying therapeutic ncRNAs represent a promising strategy for modulating macrophage polarization and restoring retinal immune homeostasis. This review integrates current knowledge on the exosome-ncRNA-macrophage axis in AMD, highlighting its role in retinal immune regulation, disease progression, and therapeutic development. Understanding this emerging signaling network may provide new opportunities to develop precision diagnostic tools and targeted therapies to prevent or slow retinal degeneration in AMD.},
}

*Exosomes/genetics/metabolism/immunology
*Macrophages/immunology/metabolism/cytology
Humans
*Macular Degeneration/genetics/pathology/immunology/metabolism
*MicroRNAs/genetics/immunology
*RNA, Long Noncoding/genetics/immunology/metabolism
Animals

@article {pmid42612872,
year = {2026},
author = {Gu, R and Hou, B and Hébert, M and Indurkar, A and Yang, Y and Chew, EY and Keenan, TDL and Lu, Z},
title = {Toward Multimodal Conversational AI for Age-Related Macular Degeneration.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.08.010},
pmid = {42612872},
issn = {2468-6530},
abstract = {PURPOSE: To evaluate OcularChat, an age-related macular degeneration (AMD)-specific multimodal large language model for interpreting color fundus photographs.

METHODS: A general-purpose multimodal large language model was fine-tuned using 705,850 simulated patient-physician dialogues paired with 46,167 AREDS images, then tested on separate AREDS and AREDS2 datasets.

RESULTS: In AREDS, OcularChat correctly classified advanced AMD, pigmentary abnormalities, and drusen size in 95.4%, 84.9%, and 67.8% of images, respectively. Retina specialists rated its responses more highly than those of the same model without fine-tuning.

CONCLUSIONS: OcularChat gives the potential to support clinician-supervised, interpretable AMD image review, research annotation, and education, requiring prospective validation before clinical deployment.},
}

@article {pmid42615798,
year = {2026},
author = {Hughes, D and Larue, AEM and Taus, P and Markert, E and Bhattacharyya, D and Atlasi, Y and Neubauer, H and Xu, H and Chen, M},
title = {A Novel Ocular Fibrosis Signature for AMD Using the Two-Stage Laser-Induced Subretinal Fibrosis Mouse Model.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {49},
doi = {10.1167/iovs.67.10.49},
pmid = {42615798},
issn = {1552-5783},
mesh = {Animals ; Mice ; Fibrosis ; Disease Models, Animal ; *Retinal Pigment Epithelium/pathology/metabolism ; Humans ; Mice, Inbred C57BL ; Choroidal Neovascularization ; Choroid/pathology/metabolism ; *Macular Degeneration/genetics/pathology/metabolism ; Male ; },
abstract = {PURPOSE: Subretinal fibrosis is a major cause of irreversible vision loss in neovascular age-related macular degeneration (AMD), yet no effective antifibrotic therapies exist due to poorly defined molecular drivers. This study aimed to derive and validate a persistent ocular fibrosis signature using the two-stage laser-induced subretinal fibrosis mouse model and to assess its translational relevance in human AMD.

METHODS: RNA sequencing (RNA-seq) was performed on retinal pigment epithelium (RPE)/choroid tissues collected at days 3, 6, and 10 following the second laser injury in the two-stage model. A novel core fibrosis signature of 88 persistently upregulated genes was observed across all time points and cross-validated in an independent mouse dataset (GSE189555) and multiple human AMD RNA-seq datasets (GSE115828, GSE146887, GSE135092), including surgically extracted choroidal neovascularization (CNV) membranes and macular RPE/choroid samples. Key signature genes were further validated by immunofluorescence in human subretinal fibrotic and age-matched tissues.

RESULTS: The novel ocular fibrosis signature was enriched in epithelial-mesenchymal transition, complement activation, and inflammatory pathways and showed choroid-specific expression with minimal retinal involvement. Cross-validation on independent chronic mouse data and multiple human AMD datasets (peripheral retina, surgically extracted CNV membranes, and macular RPE/choroid) confirmed a progressive enrichment in advanced disease stages. Immunofluorescence in human fibrotic tissue validated key genes (tenascin C, tissue inhibitor of metalloproteinases 1, and apelin receptor) and showed colocalization with myofibroblast-like cells and microglia.

CONCLUSIONS: We identified a novel, persistent, choroid-specific ocular fibrosis signature with strong cross-species conservation, highlighting fibrogenic-associated drivers and providing a valuable translational tool to understand subretinal fibrosis development and targeted antifibrotic therapies in neovascular AMD.},
}

Animals
Mice
Fibrosis
Disease Models, Animal
*Retinal Pigment Epithelium/pathology/metabolism
Humans
Mice, Inbred C57BL
Choroidal Neovascularization
Choroid/pathology/metabolism
*Macular Degeneration/genetics/pathology/metabolism
Male

@article {pmid42615809,
year = {2026},
author = {Sarwar, F and Kristoff, C and Kavoussi, S},
title = {Prevalence of Potentially Sight-Threatening Pathology Detected by Non-Mydriatic Fundus Photography in a National Diabetic Screening Platform.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-4},
doi = {10.3928/23258160-20260717-02},
pmid = {42615809},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: Hundreds, if not thousands, of non-mydriatic fundus images are acquired in primary care offices daily and uploaded for remote grading by ophthalmologists, retina specialists, and/or artificial intelligence. No prior studies of this magnitude have explored the yield of sight-threatening pathology identified on these platforms. The goal of this study is to report on the prevalence of potentially sight-threatening pathology during a 9-year experience with a single national telemedicine platform.

PATIENTS AND METHODS: This was a multicenter, non-interventional, non-masked, non-randomized, retrospective review of 1,190,754 consecutive gradable bilateral fundus exams obtained on non-mydriatic fundus cameras in the primary care setting and uploaded to a national platform. All images were interpreted by board-certified ophthalmologists and/or fellowship-trained retinal specialists.

RESULTS: In total, 44% of gradable exams were obtained on the Center Vue DRS camera, 38% on the Volk Pictor Plus, and the remainder on other cameras. Of these, 381,023 exams (32%) had evidence of pathology. Suspected moderate, severe, and proliferative diabetic retinopathy were present on 101,714 (9%), 23,988 (2%), and 30,515 (3%) exams, respectively. Macular edema was present on 27,712 exams (2%). Epiretinal membrane and age-related macular degeneration (total of exudative and dry) were present on 14,306 (1%) and 36,298 (3%) exams, respectively. Suspected glaucoma was present on 70,154 exams (6%). Papilledema, melanoma, posterior uveitis, and retinal detachment were reported in an "other pathology" category that included 116,762 exams (10%).

CONCLUSION: Routine non-mydriatic fundus screening in the primary care setting detects diabetic and non-diabetic pathology in approximately one-third of patients.},
}

@article {pmid42619175,
year = {2026},
author = {Qu, L and Cai, Y},
title = {Drug Delivery Research Related to Posterior Segment Eye Diseases: A Bibliometric Analysis of Global Trends and Therapeutic Hotspots.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683261477884},
doi = {10.1177/10807683261477884},
pmid = {42619175},
issn = {1557-7732},
abstract = {PURPOSE: Drug delivery to the posterior segment remains constrained by ocular barriers, short intraocular residence, repeated administration, and safety concerns. We mapped the global research structure of drug delivery research related to posterior segment eye diseases and identified major contributors, knowledge foundations, and therapeutic hotspots.

METHODS: English-language articles and reviews published from 1999 to 2024 were retrieved from the Web of Science Core Collection using a predefined topic search combining drug-delivery and posterior segment terms. Bibliometrix, VOSviewer, and CiteSpace were used to analyze publication growth, contributors, journals, highly cited articles, cocited references, keyword co-occurrence, citation bursts, thematic evolution, and conceptual structure.

RESULTS: The dataset contained 4,055 publications and showed sustained growth, with a higher output phase after 2020. The United States and China were the leading national contributors, while the University of Helsinki, University of Eastern Finland, Johns Hopkins University, and Emory University were prominent institutional contributors. Keyword, burst, and thematic analyses indicated a shift from permeability, pharmacokinetics, and sustained-release platforms toward macular degeneration, anti-VEGF-related therapy, injection burden, nanoparticles, long-acting systems, and clinically oriented formulation strategies.

CONCLUSION: Research has shifted from barrier characterization, pharmacokinetics, and sustained-release platforms toward macular degeneration, anti-VEGF-related therapy, injection burden, long-acting systems, and clinically oriented formulation strategies. These bibliometric signals indicate research activity rather than clinical effectiveness.},
}

@article {pmid42620072,
year = {2026},
author = {Moore, NC and Song, YE and Gulyayev, AV and Miskimen, K and Miron, P and Laux, RA and Lynn, A and Fuzzell, SL and Hochstetler, SD and Miller, D and Caywood, LJ and Clouse, JE and Herington, SD and Wang, P and Liu, Y and Dorfsman, DA and Vance, JM and Nittala, MG and Sadda, SR and Stambolian, D and Scott, WK and Pericak-Vance, MA and Haines, JL},
title = {Heritability of Age-Related Macular Degeneration in the Amish.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.08.04.26359695},
pmid = {42620072},
abstract = {PURPOSE: Age-related Macular Degeneration (AMD), a degenerative disease of aging, leads to central vision loss and has a strong genetic risk. Genetic heritability, used to quantify genetic influence on a trait, has mainly focused on twin study designs but these are vulnerable to bias. Studying relatives beyond twins is necessary to bring clarity to the genetic burden of AMD and help focus the search for additional genetic risk loci.

METHODS: Through both single nucleotide polymorphism (SNP) and pedigree-based heritability methods, the heritability of AMD was analyzed using relationship informed analyses of families from an Amish population (n = 525). AMD status was determined using the Beckman grading scale (285 controls and 240 cases). An estimate of genetic relatedness preceded SNP heritability estimation, whereas the pedigree heritability model utilized genealogical reports. Primary models were adjusted for age, sex, and population structure. A comparison of SNP- and pedigree-based models followed heritability estimation. Sensitivity models adjusting for all possible combinations of three known strong AMD genetic risk variants were constructed.

RESULTS: SNP heritability is 55% +/- 13% (p= 9.87e-06) and the pedigree heritability is 49% +/- 18% (p= 3.06e-04). The sensitivity analyses revealed that the estimates were robust to changes in the inclusion of AMD variants as covariates.

CONCLUSIONS: These heritability estimates support existing twin and SNP-based AMD heritability estimates and corroborate the substantial involvement of genetics in AMD. Adjusting for known AMD variants revealed that additional genetic contribution exists, supporting a large polygenic effect in AMD.},
}

@article {pmid42620344,
year = {2026},
author = {Tao, D and Zhou, D and Wu, M and Xie, P and Zhang, Y and Bao, J},
title = {ADORA2A activation restores lysosomal function and photoreceptor outer segment degradation in stressed retinal pigment epithelium.},
journal = {Frontiers in physiology},
volume = {17},
number = {},
pages = {1866784},
pmid = {42620344},
issn = {1664-042X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) involves early retinal pigment epithelium (RPE) dysfunction and impaired processing of photoreceptor outer segments (POS). We investigated whether ADORA2A regulates post-ingestive POS handling and lysosomal recovery under AMD-relevant stress.

METHODS: A2E-stressed ARPE-19 cells, primary porcine RPE cells, and a sodium iodate-induced mouse model were studied. ADORA2A was activated with CGS21680 and inhibited with ZM241385. POS handling, LC3B/Rubicon association with POS, lysosomal function, Rubicon depletion, chronic stress phenotypes, and retinal protection were assessed.

RESULTS: A2E increased ADORA2A expression while preserving receptor-dependent cAMP responsiveness. CGS21680 had modest effects on early POS binding and uptake but enhanced post-ingestive POS clearance and rhodopsin degradation; these effects were attenuated by ZM241385 and ADORA2A knockdown. CGS21680 increased LC3B and Rubicon association with POS-containing structures, improved lysosomal acidification, and restored DQ Green BSA processing, Cathepsin D activity, and V-ATPase-associated assembly. Bafilomycin A1 increased LC3-II and p62 accumulation and impaired CGS21680-associated POS clearance, supporting lysosome-dependent turnover. Rubicon depletion attenuated CGS21680-associated improvements in POS clearance and lysosomal acidification. CGS21680 also reduced chronic stress-associated autofluorescence, oxidative stress, apoptosis, and junctional disruption. These protective effects were reproduced in primary RPE cells. In sodium iodate-injured mice, CGS21680 preserved outer retinal structure, reduced FITC-BSA leakage, improved electroretinographic responses, and was accompanied by increased CREB phosphorylation and recovery of Cathepsin D proteolytic competence.

CONCLUSION: ADORA2A activation promotes Rubicon-associated, lysosome-dependent LC3 processing of internalized POS and restores lysosomal degradative competence, supporting ADORA2A as a potential therapeutic target for early AMD.},
}

@article {pmid42620739,
year = {2026},
author = {Hunt, PW and Sezgin, E and Olshen, AB and Murad, N and Ambayec, GC and Schneider, MF and Jabs, DA},
title = {Associations of Host Genetics and Plasma Proteomics with Incident Age-Related Macular Degeneration in Persons with AIDS.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101318},
pmid = {42620739},
issn = {2666-9145},
abstract = {OBJECTIVE: To evaluate whether common plasma proteomic pathways connect host genetic risk factors to incident age-related macular degeneration (AMD) in persons with AIDS.

DESIGN: Nested case-control study.

PARTICIPANTS: Subset of persons enrolled in the Longitudinal Study of Ocular Complications of AIDS.

METHODS: Baseline cryopreserved plasma specimens were assayed for inflammatory and cardiovascular proteins using the Olink Inflammation Explore Panels 1 to 2 and the Cardiometabolic Explore Panels 1 to 2. Age-related macular degeneration‑associated genetic variants were assessed using Applied Biosystems Taqman probes. Baseline proteomic profiles for 26 persons who subsequently developed incident intermediate-stage AMD after 5 to 10 years of follow-up and 49 controls without AMD matched for age, natal sex, race/ethnicity, and follow-up duration were compared. False discovery rate correction was performed with the Storey Q method, and both unsupervised gene ontology pathway enrichment and dedicated pathway analyses were performed. Age-related macular degeneration‑associated plasma protein levels were compared between AMD high-risk and AMD low-risk genotypes.

MAIN OUTCOME MEASURES: Incident intermediate-stage AMD.

RESULTS: 371 (26%) of 1448 evaluable plasma proteins were associated with incident AMD at the false discovery rate Q < 0.05 threshold. Hallmark pathways significantly enriched in incident AMD included inflammation, complement, and fatty acid metabolism pathways. Complement factor H, a complement activation regulating protein with a genetic association with AMD, levels appeared to be associated with AMD (adjusted odds ratio: 0.12 per 2-fold increase, P = 0.055). Several related proteins in the Hallmark complement pathway were strongly associated with AMD, 16 including CD46, platelet-derived growth factor β, chemokine ligand 1, and CCL5 (all Q < 0.05), which have been linked to AMD risk in genetic studies. Among cholesterol homeostasis-related genes, lipoprotein lipase was associated with a decreased risk of AMD (adjusted odds ratio: 0.18 per 2-fold increase, Q = 0.008). Participants with AMD high-risk genotypes had elevated levels of shared proteins in inflammatory, complement, and fatty acid metabolism pathways.

CONCLUSIONS: Levels of several plasma proteins linked to the complement pathway and cholesterol homeostasis, which have been linked to AMD risk in genetic studies, are associated with incident AMD in people with AIDS. Plasma levels of shared inflammatory proteins linked to several different genetic AMD risk factors predicted AMD risk, suggesting common immunologic mechanisms linking genetic risk factors for AMD.

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

@article {pmid42621091,
year = {2026},
author = {Mohammadi, SS and Sikora, H and Bisen, J and Kim, H and Drakopoulos, M and Nadel, A and Hamzeh, N and Bains, H and Lyon, AT and Mirza, RG},
title = {Functional and Anatomic Outcomes at 12 Months After Switching to Faricimab in Treatment-Recalcitrant Neovascular Age-Related Macular Degeneration.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261472089},
pmid = {42621091},
issn = {2474-1272},
abstract = {Purpose: To evaluate functional and anatomic outcomes over 12 months in patients with recalcitrant neovascular age-related macular degeneration (nAMD) whose treatment was transitioned to faricimab. Methods: This retrospective observational study included 36 patients (41 eyes) with treatment-recalcitrant nAMD previously treated with bevacizumab, ranibizumab, or aflibercept. Patients received 4 monthly intravitreal faricimab injections followed by individualized treatment intervals. Best-corrected visual acuity (BCVA), optical coherence tomography (OCT) images, and swept-source OCT angiography images were assessed at baseline, 6 months, and 12 months. Anatomic features evaluated included intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), macular neovascularization (MNV), and geographic atrophy (GA). Results: Mean (±SD) BCVA remained stable over the 12-month period (baseline, 0.289 ± 0.350 logMAR; 12 months, 0.306 ± 0.394 logMAR; P = .41). Treatment intervals increased from a mean of 5.29 weeks prior to the switch to faricimab to 7.58 weeks afterward. Anatomically, the proportion of eyes without IRF or SRF improved from 34.14% at baseline to 74.68% at 12 months. A significant reduction in PED maximum height was observed at 6 months, along with decreases in mean PED height and volume. MNV metrics demonstrated a significant decline in vessel area density at 6 months (P = .031), although no sustained significant changes were observed at 12 months. GA size increased by a mean of 0.41 mm[2]/year over the study period (P = .026). Conclusions: Switching to faricimab in treatment-recalcitrant nAMD maintained visual acuity, improved anatomic outcomes, and significantly extended injection intervals. These findings underscore faricimab's efficacy in managing refractory nAMD cases.},
}

@article {pmid42621295,
year = {2026},
author = {Mares, V and Sacu, S and Frank-Publig, S and Eidenberger, A and Fuchs, P and Coulibaly, LM and Baratsits, M and Faustmann, G and Gumpinger, M and Sükei, E and Bogunovic, H and Reiter, GS and Leingang, O and Miere, A and Creuzot-Garcher, C and Kodjikian, L and Gualino, V and Wolff, B and Scheschy, U and Schmidt-Erfurth, U},
title = {Early Structure-Function Correlates in Neovascular Age-Related Macular Degeneration Using Artificial Intelligence-Derived OCT Biomarkers.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101281},
pmid = {42621295},
issn = {2666-9145},
abstract = {PURPOSE: To correlate automated artificial intelligence-based retinal fluid quantification with ellipsoid zone (EZ) thickness and loss, macular neovascularization (MNV) type, and visual function.

DESIGN: This is a post hoc analysis of a prospective, real-world, multicenter clinical trial.

SUBJECTS: Patients with active neovascular age-related macular degeneration (nAMD) were included.

METHODS: Best-corrected visual acuity (BCVA), measured using the ETDRS chart, OCT, OCT angiography, and microperimetry, were collected by the same certified examiners. Subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) volumes for the central 1- and 6- mm areas were calculated at baseline using the Fluid Monitor (Retinsight) on Spectralis OCT (Heidelberg Engineering). An automated algorithm segmented EZ thickness and loss detectable after fluid resolution at month 1.

MAIN OUTCOME MEASURES: Fluid volumes were associated with MNV type, EZ thickness and loss, retinal sensitivity, and BCVA using univariate and multivariate regression models and Wilcoxon rank-sum tests with bootstrapped confidence intervals. Spearman correlation was used to analyze retinal sensitivity and EZ loss.

RESULTS: Two hundred ninety eyes from 290 consecutive patients with active MNV were included in the study at baseline. Macular neovascularization type 1 was the most prevalent in this cohort. Comparing MNV types, lower amounts of IRF were found in type 1 (all P < 0.001) and lower amounts of SRF for type 3 (all P < 0.05), in the central 1- and 6-mm areas. A decreased BCVA at month 1 was associated with IRF in the central 1 mm at baseline (-6.8 letters/100 nL; P < 0.001). Intraretinal fluid and PED volumes at baseline were correlated with EZ loss at month 1 in the central 6 mm. High fluid volumes of IRF, SRF, and PED in the central 1- and 6- mm areas also correlated with decreased mean retinal sensitivity (all P < 0.01). Ellipsoid zone loss in the central 1- and 6-mm area correlated with decreased retinal sensitivity (all P < 0.01).

CONCLUSION: Retinal fluid volumes in nAMD are triggered by MNV types and correlate with photoreceptor integrity and visual function, with the impact depending on the fluid compartment. Although fluid is central to disease monitoring, a more comprehensive approach to structural-functional assessment in nAMD is of interest.

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

@article {pmid42621341,
year = {2026},
author = {Eandi, CM and Snyder, VC and Grieve, K and Gocho, K and Chaumette, C and Castro-Farias, D and Norberg, N and Eddy, G and Friberg, TR and Eller, AW and Dansingani, KK and Martel, JN and Chhablani, J and Sahel, JA and Paques, M and Rossi, EA},
title = {High-Resolution and Multimodal Structural Phenotyping of Intermediate and Advanced Non-Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101307},
pmid = {42621341},
issn = {2666-9145},
abstract = {PURPOSE: To characterize structural phenotypes in intermediate and advanced non-neovascular age-related macular degeneration (AMD) using flood-illumination adaptive optics (FIAO) and to explore their relationship with established multimodal imaging biomarkers, including OCT-based atrophy classifications.

DESIGN: Prospective, cross-sectional observational study.

SUBJECTS: A total of 208 eyes from 117 patients (mean age 74 years; 63% female) with intermediate AMD (iAMD) or geographic atrophy (GA) were enrolled. Eligible participants had visual acuity ≥20/63, refractive error between -6 and +2 diopters, and sufficient media clarity for high-quality imaging.

METHODS: Participants underwent multimodal imaging, including color fundus photography, spectral-domain OCT, infrared reflectance, fundus autofluorescence, and FIAO. Structural phenotypes (drusen, subretinal drusenoid deposits, pigmentary changes, and GA margins) were assessed qualitatively across modalities. Flood-illumination adaptive optics features were compared with OCT-based atrophy classifications (incomplete and complete retinal pigment epithelium and outer retinal atrophy [iRORA and cRORA]) using descriptive analyses and cross-tabulation.

MAIN OUTCOME MEASURES: Prevalence and multimodal characteristics of AMD structural phenotypes, and their correspondence with FIAO features.

RESULTS: Drusen and pigmentary abnormalities were detected in the majority of eyes across modalities, with variability in prevalence depending on imaging technique. Flood-illumination adaptive optics identified drusen in 70% of eyes revealing a consistent reflectivity pattern of hyperreflective borders and hyporeflective centers. Hyporeflective clumps corresponding to pigmentary changes were always observed on FIAO, frequently localizing to areas of atrophy or transition zones. Distinct FIAO-defined GA border phenotypes were observed, including well-demarcated and indistinct margins. In descriptive cross-tabulation, well-demarcated FIAO borders were more frequently associated with OCT-defined cRORA, whereas indistinct or hyporeflective margins were with iRORA.

CONCLUSIONS: Flood-illumination adaptive optics provides high-resolution visualization of structural features in iAMD and GA, revealing distinct patterns of drusen, pigmentary changes, and atrophic margins. While certain FIAO features show qualitative correspondence with OCT-defined atrophy stages, these relationships remain descriptive. Further quantitative and longitudinal studies are needed to determine their clinical relevance and role in disease characterization.

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

@article {pmid42621407,
year = {2026},
author = {Mai, J and Reiter, GS and Riedl, S and Vogl, WD and Sadeghipour, A and McKeown, A and Foos, E and Schwartz, R and Sacu, S and Bogunovic, H and Schmidt-Erfurth, U},
title = {Predictive Value of Perilesional Fundus Autofluorescence Patterns and OCT-Based Ellipsoid Zone/Retinal Pigment Epithelium Loss Ratios in Geographic Atrophy Growth Rates.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101306},
pmid = {42621407},
issn = {2666-9145},
abstract = {PURPOSE: To investigate the association between perilesional fundus autofluorescence (FAF) patterns and ellipsoid zone (EZ)/retinal pigment epithelium (RPE) loss ratio on OCT in geographic atrophy (GA) and their predictive value on disease progression and therapeutic response to pegcetacoplan.

DESIGN: Post hoc analysis of 2 prospective randomized controlled phase III clinical trials.

SUBJECTS: Patients with GA secondary to age-related macular degeneration.

METHODS: OCT and FAF images from the OAKS (NCT03525613) and DERBY (NCT03525600) trials, 2 phase III, randomized controlled clinical trials of intravitreal pegcetacoplan for the treatment of GA secondary to age-related macular degeneration, were analyzed. Retinal pigment epithelium and EZ loss were measured on OCT by previously validated deep learning-based algorithms. Perilesional FAF patterns were graded at a centralized reading center from the trials. Pooled study eyes and fellow eyes that met the inclusion/exclusion criteria were divided into 4 quartiles based on baseline EZ/RPE loss ratios on OCT. The distribution of FAF patterns between the quartiles was analyzed. The association between baseline FAF pattern and disease progression and therapeutic response to pegcetacoplan was investigated.

MAIN OUTCOME MEASURES: Distribution of FAF patterns between EZ/RPE loss ratio quartiles, mean change in FAF-based GA growth, RPE, and EZ loss on OCT.

RESULTS: Fundus autofluorescence and OCT gradings were available for 1317 study and fellow eyes from both trials pooled together. The focal pattern showed smaller ratios (P < 0.001), whereas the diffuse-trickling pattern was present in higher ratios (P = 0.005) at baseline. All other patterns showed no correlation with EZ/RPE loss ratios. There was an association of the focal and the diffuse-trickling pattern with FAF-based GA progression and OCT-based RPE loss, but not with OCT-based EZ loss. A greater treatment effect was identified in eyes with the diffuse-trickling pattern, which was present in a small number of eyes.

CONCLUSIONS: The focal and diffuse-trickling FAF patterns were associated with RPE loss; however, perilesional FAF patterns were not associated with photoreceptor degeneration. There was a greater treatment effect in eyes with the diffuse-trickling pattern, presenting with higher EZ/RPE loss ratios on OCT in a small subgroup.

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

@article {pmid42621660,
year = {2026},
author = {Yao Jin, L and Selvam, EGP and Mei, Q and Luu, CD and Yap, YHY and Teh, DBL},
title = {Advancing Treatment of Degenerative Eye Diseases at the Nanoscale.},
journal = {Smart medicine},
volume = {5},
number = {4},
pages = {e70050},
pmid = {42621660},
issn = {2751-1871},
abstract = {Degenerative ocular diseases are characterized by a convergence of molecular perturbations, including oxidative stress, chronic inflammation, failure of proteostasis, mitochondrial dysfunction, abnormal angiogenic signaling, and biomechanical remodeling. The eye's unique architecture, sealed by the blood-retina barrier, presents formidable anatomical and cellular topological challenges to achieving long-term curative therapeutics. Nanotechnology offers an advantage in potential therapy: by utilizing carriers in the nanometer size range and leveraging on appropriate surface modifications, it can effectively overcome these physiological barriers for enhanced, controlled, and targeted treatment. Clinical and preclinical systems such as antioxidant nanoparticles, sustained release implants, anti-angiogenic nanoplatforms, multifunctional nanocomposites, and regenerative scaffolds illustrate how nanotechnology can overcome limitations in bioavailability, tissue penetration, and pathway specificity in degenerative ocular diseases. Diagnostic advances that include plasmonic contrast agents, quantum dots, graphene biosensors, smart contact lenses, and photothermal neuromodulators further demonstrate continuous molecular surveillance and responsive intervention. Emerging materials such as DNA origami and magnetoelectric nanosystems expand this capability by enabling direct modulation of transcriptional, metabolic, and neuroelectrical pathways. Together, these developments position nanotechnology as a powerful strategy for addressing the molecular origins of ocular degeneration while also highlighting ongoing challenges in long term safety, device stability, manufacturing reproducibility, and regulatory standardization.},
}

@article {pmid42608930,
year = {2026},
author = {Kurysheva, NI and Maslova, EV},
title = {[Glaucoma and age-related macular degeneration: challenges and prospects for prevention and treatment of combined pathology. Part 1. Epidemiology and pathogenesis].},
journal = {Vestnik oftalmologii},
volume = {142},
number = {4},
pages = {112-119},
doi = {10.17116/oftalma2026142041112},
pmid = {42608930},
issn = {0042-465X},
mesh = {Humans ; *Macular Degeneration/epidemiology/physiopathology/therapy/prevention & control/diagnosis/etiology ; *Glaucoma/epidemiology/physiopathology/therapy/prevention & control/diagnosis/complications ; Risk Factors ; },
abstract = {Glaucoma and age-related macular degeneration are the leading causes of irreversible vision loss in individuals over 60 years of age. This review consolidates current data on the epidemiology, shared genetic factors, and pathophysiological mechanisms underpinning their coexistence, and outlines prospects for personalized prevention and therapy. Common modifiable risk factors comprise cigarette smoking, arterial hypertension, and dyslipidemia. Chorioretinal hypoperfusion, mitochondrial dysfunction, activation of the NLRP3 inflammasome, and impaired glymphatic elimination of amyloid contribute to neurodegeneration both in the macula and in the optic nerve area. Treatment prospects include comprehensive vascular and neuroprotective regimens, targeted complement modulation, and the use of polygenic risk scores for patient stratification and longitudinal monitoring.},
}

Humans
*Macular Degeneration/epidemiology/physiopathology/therapy/prevention & control/diagnosis/etiology
*Glaucoma/epidemiology/physiopathology/therapy/prevention & control/diagnosis/complications
Risk Factors

@article {pmid42608931,
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 = {[The effect of angiogenesis inhibitor therapy on the risk of fibrosis formation in neovascular age-related macular degeneration and potential strategies for its prevention].},
journal = {Vestnik oftalmologii},
volume = {142},
number = {4},
pages = {120-126},
doi = {10.17116/oftalma2026142041120},
pmid = {42608931},
issn = {0042-465X},
mesh = {Humans ; *Angiogenesis Inhibitors/pharmacology/administration & dosage ; Fibrosis/prevention & control ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Macular Degeneration/drug therapy ; Angiopoietin-2/metabolism ; *Retina/pathology ; *Wet Macular Degeneration/drug therapy ; },
abstract = {Numerous randomized clinical trials and real-world clinical practice have demonstrated the effect of angiogenesis inhibitors (anti-VEGF agents) on the activity and growth of neovascular complexes in neovascular age-related macular degeneration (nAMD), with a proven reduction in the risk of macular fibrosis, the incidence of which decreased from 39-100% in the "pre-antiangiogenic era" to 20.4-61.4% after introduction of anti-VEGF therapy. The main factors determining the risk of subretinal fibrosis are disease activity, time of therapy initiation, treatment regimen, its regularity, and the type of drug. Variations in retinal thickness and the volatility of specific fluid compartments lead to an increase in the volume of subretinal hyperreflective material (SHRM) and prevent full restoration of the integrity of the ellipsoid zone. Extensive research into 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 the production of TGF-β and CTGF, and cross-talk with classical fibrotic pathways. The synergism between Ang-2 and VEGF-A stimulates subretinal scarring and highlights the high potential of bispecific therapy for improving clinical outcomes in patients with nAMD. Compensatory activation of Ang-2 during anti-VEGF monotherapy may support 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 confirmed by a significant reduction in the volume of SHRM - a key precursor to fibrotic changes.},
}

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

@article {pmid42601635,
year = {2026},
author = {Chen, N and Liu, Y and Chen, Z and Xiang, Y and Yu, H},
title = {Integrative genomic and proteomic analyses identify candidate genetic loci and genetically supported proteins in age-related macular degeneration.},
journal = {Eye and vision (London, England)},
volume = {13},
number = {1},
pages = {},
pmid = {42601635},
issn = {2326-0254},
support = {8227041127//the launch fund of Guangdong Provincial People's Hospital for NSFC/ ; 82301205//National Natural Science Foundation of China/ ; 2023B1515120028//Basic and Applied Basic Research Foundation of Guangdong Province/ ; 2024T170185//China Postdoctoral Science Foundation/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of visual impairment; however, robust drug targets for primary prevention remain elusive. This study aimed to identify candidate genetic loci and putative genetically supported proteins for AMD through integrative genomics and proteomics.

METHODS: A genome-wide association study (GWAS) meta-analysis (28,543 cases and 1,072,092 controls) was performed to identify risk loci, followed by proteome-wide Mendelian randomization (MR), colocalization, and multi-omics summary-data-based MR with heterogeneity in dependent instruments (SMR-HEIDI) analyses to infer genetically supported proteins. Functional characterization included gene enrichment, single-cell RNA sequencing, mediation across 731 immunophenotypes, and a mouse knockout assessment. Druggability was evaluated using the Drug-Gene Interaction Database.

RESULTS: The GWAS meta-analysis identified 10 candidate genetic loci for AMD (including three previously reported and seven newly identified loci). Proteome-wide MR and colocalization analyses uncovered 23 genetically supported plasma proteins (11 risk and 12 protective factors). Multi-omics SMR-HEIDI analysis prioritized LAMC2 and PLTP as first-tier risk genes, which was consistently supported across protein, expression, and methylation levels. Single-cell RNA sequencing revealed cell-type-specific enrichment of key genes in monocytes and stromal/progenitor-like cells within AMD retinas, and subsequent mediation analysis identified specific immune traits, most notably regulatory T-cell subsets, as potential partial mediators of AMD risk. Druggability assessment identified 15 target genes, and bioinformatic enrichment nominated cyclophosphamide. Given the toxicity profile of cyclophosphamide, this computational finding serves strictly as a pathway indicator, reinforcing the broader therapeutic relevance of modulating the identified immune-related targets.

CONCLUSION: Our integrative analyses identified candidate genetic loci and genetically supported proteins for AMD, providing a foundation for translating genomic findings toward primary prevention. The exploratory nature of this study highlights the need to experimentally validate the proposed targets and underlying mechanisms.},
}

@article {pmid42601984,
year = {2026},
author = {Lai, A and Issa, M and Ali, A and Pereira, A and Ali, AA and Chhablani, J and Yan, P},
title = {Aging-Related Choroidal Heterogeneity and Loss: An Investigative Global Human Choroidal Thickness Review (ARCHLIGHT Study).},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261457969},
pmid = {42601984},
issn = {2474-1272},
abstract = {PURPOSE: To synthesize current evidence on the pathophysiology, clinical relevance, and implications for age-related choroidal thinning.

METHODS: A systematic literature search of relevant publications was conducted across MEDLINE, Embase, and Cochrane Library, up to and including May 2024. Identified studies reported choroidal thickness changes with aging. Data on subfoveal choroidal thickness, choroidal vascularity index, and associated factors (ethnicity, systemic disease, axial length) were analyzed (PROSPERO ID: CRD420251041101).

RESULTS: Choroidal thickness declines with age, with ethnicity-specific rates ranging from -0.93 µm/year in Spanish cohorts to -4.00 µm/year in Chinese populations. Age-related choroidal thinning correlates with retinal and neurodegenerative pathologies, including glaucoma (nasal choroidal thinning >250 µm in older adult patients), myopic maculopathy (subfoveal choroidal thickness <100 µm in high myopia), and Alzheimer disease (subfoveal choroidal thickness 169 µm vs 253 µm in control patients). Enhanced depth imaging optical coherence tomography (OCT) and swept-source OCT reveal preferential vascular loss (choroidal vascularity index <30%) and stromal atrophy. Systemic risks, such as hypertension or smoking, accelerate choroidal thinning.

CONCLUSIONS: Age-related choroidal thinning exists on a continuum between physiologic aging and pathology, with implications for retinal and systemic health. Future prospective studies will help determine diagnostic thresholds (subfoveal choroidal thickness <200 µm in nonmyopic adults >60 years or rapid thinning beyond ethnic normative values), management recommendations for high-risk cohorts (glaucoma, age-related macular degeneration, high myopia), and therapeutic considerations for monitoring of choroidal thickness changes from moderate- to low-certainty evidence.},
}

@article {pmid42602093,
year = {2026},
author = {Taylor, CX and Reed, H and Talcott, KE and Singh, RP},
title = {Incidence and Recovery of 15-Letter Loss of Visual Acuity in Patients With Neovascular Age-Related Macular Degeneration on Antivascular Endothelial Growth Factor Therapy.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261472092},
pmid = {42602093},
issn = {2474-1272},
abstract = {PURPOSE: To describe how 15-letter loss of visual acuity (VA) in patients with neovascular age-related macular degeneration (nAMD) results in transient fluctuations in vision. In addition, to compare recoverability of letter loss in patients treated with antivascular endothelial growth factor (anti-VEGF) with untreated patients.

METHODS: Patients with previously untreated nAMD in the Comparisons of AMD Treatments Trials were assigned to transient and nontransient groups based on recovery of baseline best-corrected VA within 8 weeks. Magnitude of recoverable letter loss was modeled via linear regression.

RESULTS: Two hundred fifty-three of 1018 patients (25%) experienced 15-letter loss: 68 transient (7%) and 185 nontransient (18%). Two-year outcomes were better without 15-letter loss (+12 letters, 95% CI, 11-13, n = 772) compared with transient 15-letter loss (+0.4 letters, 95% CI, -4 to 5) and nontransient 15-letter loss (-14 letters, 95% CI, -17 to -12). Nontransient losses up to -2.5 letters were expected to be recoverable (95% CI, -6.0 to 1.0). Fifteen-letter loss was associated with smoking (P = .02) and poor nontransient outcomes with higher blood pressure (P = .04).

CONCLUSIONS: Patients experiencing transient and nontransient 15-letter loss differed significantly in outcomes. Nontransient losses were not expected to be recoverable. These findings may help guide the selection of measures in clinical trial design.},
}

@article {pmid42606042,
year = {2026},
author = {Muth, DR and Venkataraman, AP and Dominguez-Vicent, A and Petrovski, G and Williams, PA and Quérat, L and Locri, F and Zweifel, SA and Kvanta, A},
title = {Regional growth kinetics of geographic atrophy in age-related macular degeneration with and without fovea-sparing.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70229},
pmid = {42606042},
issn = {1755-3768},
support = {//Ögonfonden, Sweden/ ; },
abstract = {PURPOSE: Fovea-sparing geographic atrophy (GA) patients retain near-normal central vision. To better understand GA progression in relation to the fovea, we performed a semi-automated image analysis of regional atrophy growth in a long-term GA natural-history cohort.

METHODS: Prospective-observational, single-centre-study (02/2013-07/2025) at the Division of Eye and Vision, Karolinska Institutet/St. Erik Eye Hospital, Stockholm, Sweden. Longitudinal square-root-transformed GA area and distance-growth rates [mm/year] in all retinal quadrants were calculated from fundus autofluorescence images. Eyes were stratified based on best-corrected visual acuity: fovea-sparing (≥65 ETDRS) and fovea-involving (<65 ETDRS).

RESULTS: 65 eyes (65 patients) presented fovea-sparing and 91 eyes (91 patients) fovea-involving. Median follow-up was 18 months (range: 5-125). The fovea-involving group decreased in BCVA (Wilcoxon, p < 0.001). Total area growth was faster for fovea-sparing than fovea-involving lesions: 0.34 vs. 0.26 (Mann-Whitney U, p = 0.0019). The same was true for the superior, inferior, and temporal quadrants (Mann-Whitney U, all p < 0.0472). Fovea-sparing lesions showed slower distance growth towards the fovea than outwards in all quadrants: superior 0.09 vs. 0.21; nasal 0.08 vs. 0.18; inferior 0.06 vs. 0.17; temporal 0.09 vs. 0.20 (Wilcoxon, all p < 0.001). Lesions closer to the fovea (≤500 μm) at baseline showed decreased regional growth towards the fovea. Outwards growth was not related to lesion location.

CONCLUSIONS: In this longitudinal cohort, fovea-sparing lesions showed faster total and regional growth than fovea-involving lesions, mainly caused by a faster outward expansion component. Location 500 μm or closer to the fovea resulted in slower growth, which supports a foveal self-protecting mechanism. These are relevant findings for patients with fovea-sparing lesions.},
}

@article {pmid42607745,
year = {2026},
author = {Futterknecht, S and Riedl, S and Mai, J and Arabi, S and Hall, U and Bogunovic, H and Fritsche, LG and Rueckert, D and Menten, MJ and Sacu, S and Schmidt-Erfurth, U and Sivaprasad, S and Lotery, A and Pfau, M},
title = {Lesion-Centered Functional Trajectories Reveal Early Retinal Sensitivity Decline in Intermediate AMD: PINNACLE Study Report 15.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.017},
pmid = {42607745},
issn = {1879-1891},
abstract = {PURPOSE: To characterize lesion-centered functional decline in intermediate age-related macular degeneration (iAMD), including measurement variability, spatial vulnerability, pre-detection functional changes, and lesion-specific sensitivity trajectories.

DESIGN: Longitudinal analysis of microperimetry from the prospective, multicenter PINNACLE study (NCT06682455).

PARTICIPANTS: Overall, 264 participants contributing 422 eyes were included. Focal event analyses included 338 OCT-defined events from 131 eyes of 113 participants.

METHODS: Participants underwent mesopic microperimetry using a standard 24-point grid. OCT-defined events triggered lesion-centered 5-point testing. Repeatability was assessed using linear mixed-effects models. Lesion-centered sensitivity trajectories were estimated using spatiotemporal generalized additive mixed models incorporating measured post-detection focal-grid data and spatially interpolated pre-detection standard-grid data. A secondary piecewise linear mixed-effects model quantified changes before and after event detection.

MAIN OUTCOME MEASURES: Point-wise microperimetry repeatability, sensitivity loss of ≥7 dB, relative and absolute scotoma, and model-estimated lesion-centered sensitivity trajectories.

RESULTS: The point-wise coefficient of repeatability was 7.61 dB (95% confidence interval [CI], 7.58-7.64) for standard-grid testing and 13.00 dB (95% CI, 12.76-13.21) for lesion-centered testing. The 338 events comprised 240 ellipsoid zone/interdigitation zone loss events, 85 drusen-collapse events, and 13 subretinal-fluid events. Within 2 years, the risk of sensitivity loss of ≥7 dB was lower at parafoveal (hazard ratio, 0.66; 95% CI, 0.51-0.84) and perifoveal locations (hazard ratio, 0.68; 95% CI, 0.53-0.87) than at foveal locations. Model-estimated sensitivity at ellipsoid zone/interdigitation zone loss sites declined before detection by 0.57 dB/year (95% CI, 0.25-0.89 dB/year) and continued after detection, reaching 0.94 dB/year (95% CI, 0.55-1.34 dB/year) during the late post-detection period. Drusen-collapse sites showed no clear longitudinal decline. Subretinal-fluid events showed an immediate loss of 2.18 dB (95% CI, 0.84-3.53), followed by early decline and possible later improvement. Matched control locations remained stable.

CONCLUSIONS: Localized functional decline in iAMD is characterized by measurement variability, central spatial vulnerability, and lesion-specific trajectories. Model-estimated sensitivity decline was most evident at sites of ellipsoid zone/interdigitation zone loss. These findings support structurally and spatially informed microperimetry endpoints while highlighting substantial measurement variability.},
}

@article {pmid42607856,
year = {2026},
author = {Chou, SJ and Wang, CH and Tsai, PH and Hsiao, YJ and Ou-Yang, H and Fang, WC and Tsai, HY and Shia, KS and Song, JS and Wu, CH and Lee, N and Tsai, ML and Hwang, DK and Hsu, CC and Chen, SJ and Chiou, SH and Lin, TC and Yang, YP},
title = {Inhibition of CXCR4-Induced Angiogenesis to Block Choroidal Neovascularization and Restore Retinal Function in Age-Related Macular Degeneration by In Silico-Selected Small Molecules.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {179236},
doi = {10.1016/j.ejphar.2026.179236},
pmid = {42607856},
issn = {1879-0712},
abstract = {The chemokine receptor CXCR4 has been recognized as a pivotal mediator of cytokine-driven angiogenesis. Wet age-related macular degeneration (wet-AMD) is characterized by choroidal neovascularization (CNV) leading to vision loss. However, the current anti-VEGF therapy remains limited by recurrent CNV in refractory wet-AMD. Herein we developed small-molecule inhibitors targeting CXCR4-mediated neovascularization in wet-AMD. Employing computational molecular docking simulations for candidate screening, BPRCX807 exhibited superior binding affinity as a CXCR4 antagonist relative to other compounds tested. A laser-induced wet-AMD murine model was established, demonstrating subretinal CNV and upregulation of proteins implicated in CXCR4 signaling and angiogenesis. Retinal structural alterations and CNV-progression were monitored via real-time fluorescein angiography and optical coherence tomography (OCT), revealing that BPRCX807 treatment significantly attenuated angiogenesis compared to conventional anti-VEGF therapy. Retinal safety evaluation further indicated that BPRCX807 administration did not induce detectable retinal toxicity or structural abnormalities. Ex vivo choroid sprouting assays corroborated the reduction of vascular leakage and CNV-formation by BPRCX807. The visual-functional electroretinographic evaluations indicated that, while anti-VEGF agents produced modest functional improvements, BPRCX807 achieved superior restoration of retinal visual function. Notably, bioinformatic analyses supported that inhibition of CXCR4 signaling effectively suppressed VEGF-driven and cytokine-mediated angiogenic pathways. Finally, biomolecular simulations combined with predictive signaling-pathway analyses suggested that BPRCX807 modulates multiple VEGF-regulatory signaling cascades, thereby enhancing its inhibitory effects on VEGF expression and downstream angiogenesis. Collectively, these computational and experimental data demonstrate that BPRCX807 disrupts CXCR4 receptor interactions and suppresses angiogenic factor expression via inhibition of the CXCR4/p-AKT signaling pathway, representing a promising therapeutic approach for wet-AMD.},
}

@article {pmid42607929,
year = {2026},
author = {Shmushkevich, SB and Bajrami, S and Grand, ZA and Tijerina, JD and Williams, BK and Rothman, AL},
title = {Risk of New Glaucoma Diagnosis and Surgery for Patients with Intravitreal Injections in the TriNetX Database.},
journal = {Ophthalmology. Glaucoma},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ogla.2026.08.002},
pmid = {42607929},
issn = {2589-4196},
abstract = {OBJECTIVE: To quantify the long-term risk of incident glaucoma and of undergoing glaucoma surgery associated with intravitreal injection therapy using a large electronic health record network.

DESIGN: Retrospective cohort study.

SUBJECTS: Patients with no prior glaucoma diagnosis in the TriNetX US Collaboration Network seen between 03/14/2006-03/14/2026 with either exudative age-related macular degeneration (AMD) and intravitreal injection or nonexudative AMD with no history of injection.

METHODS: Patients with exudative AMD who received intravitreal injections (Current Procedural Terminology 67028) were compared with patients with nonexudative AMD. Patients with retinal vascular occlusions, proliferative diabetic retinopathy, retinal ischemia, pseudoexfoliation syndrome or pigment dispersion syndrome were excluded. Cohorts were propensity score matched 1:1 for age, sex, race, ethnicity, and systemic comorbidities. Time-to-event analyses were performed, and effect estimates included risk ratios (RR), odds ratios (OR), and hazard ratios (HR).

MAIN OUTCOME MEASURES: New glaucoma diagnosis (International Classification of Diseases-10 H40) and glaucoma surgical interventions.

RESULTS: After exclusions and matching, each cohort contained 27,967 patients. Incident glaucoma occurred in 15.1% (4,218/27,967) of injection patients versus 12.9% (3,621/27,967) of controls (RR 1.17; OR 1.19; HR 1.08, p<0.001). Any glaucoma surgery occurred in 1.6% (435/27,967) of injection patients compared with 0.8% (236/27,967) of controls (RR 1.84; OR 1.86; HR 1.66, p<0.001). Patients with intravitreal injection were more likely to undergo glaucoma tube implantation (p<0.001), laser trabeculoplasty (p<0.001), cyclodestructive procedures (p=0.001), and trabeculectomy (p=0.03). Incisional angle surgery trended toward significance (p=0.054).

CONCLUSIONS: In a large cohort, intravitreal injection therapy for exudative AMD was associated with higher risks of incident glaucoma and glaucoma surgery compared with matched nonexudative AMD controls, corresponding to a number needed to harm of approximately 47 for incident glaucoma.},
}

@article {pmid42608919,
year = {2026},
author = {Andreeva, IV and Stoyukhina, AS and Smolin, SA and Hamza, V},
title = {[Modern diagnostic possibilities for peripapillary neovascular membranes. Report 1. OCT diagnostic signs].},
journal = {Vestnik oftalmologii},
volume = {142},
number = {4},
pages = {26-36},
doi = {10.17116/oftalma202614204126},
pmid = {42608919},
issn = {0042-465X},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Female ; Male ; *Retinal Neovascularization/diagnosis/etiology ; Diagnosis, Differential ; Fluorescein Angiography/methods ; Aged ; *Choroid/pathology/diagnostic imaging ; Retinal Pigment Epithelium/pathology/diagnostic imaging ; Middle Aged ; *Optic Disk/pathology ; },
abstract = {UNLABELLED: Peripapillary subretinal neovascular membranes (SRNVMs) develop due to neovascular age-related macular degeneration (nAMD), retinal angioid streaks, inflammatory diseases, congenital optic disc anomalies, and other causes. Diagnosis of peripapillary SRNVMs relies on multimodal imaging, with optical coherence tomography (OCT) being the main method.

OBJECTIVE: The study aimed to identify differential diagnostic signs of peripapillary SRNVMs of various etiologies according to OCT data.

MATERIALS AND METHODS: We examined 48 patients with active peripapillary SRNVMs. All patients underwent OCT, including OCT angiography. Quantitative and qualitative characteristics were evaluated.

RESULTS: In nAMD, peripapillary SRNVMs presented as fibrovascular retinal pigment epithelium (RPE) detachment (p=0.05), with a "double-layer" sign and drusen in one-third of cases (p=0.017). Subfoveal choroidal thickness in patients with nAMD did not differ significantly from the age-related norm (p=0.473 and p=0.384 for the study and fellow eyes, respectively); the inner choroidal surface had a smooth profile (p=0.033), and the Bruch membrane was preserved (p=0.033). In angioid streaks, OCT visualized a thin choroid with folding of the inner surface (p<0.0001) and ruptures of the Bruch membrane (p<0.0001). In the area of peripapillary SRNVM, choroidal thickness was lower than in patients with nAMD (p=0.024) and pachychoroid spectrum diseases (p<0.0001). In pachychoroid-related SRNVMs, choroidal thickness in the SRNVM area and subfoveally, both in the study and fellow eyes, significantly exceeded the values observed in SRNVMs of other etiologies (p<0.0001). RPE changes mainly presented as a shallow local detachment (p=0.02) with a saw-tooth contour and no defects. Subretinal hyperreflective material in the SRNVM area was also absent (p=0.02), but isolated subretinal fluid predominated in pachychoroid neovasculopathy (p=0.004), whereas a combination of subretinal and intraretinal fluid was more prevalent in chronic central serous chorioretinopathy.

CONCLUSION: To correctly determine the type of peripapillary SRNVM, it is necessary to pay primary attention to the condition of the choroid and Bruch membrane, the presence of drusen and subretinal hyperreflective material in the SRNVM area and subfoveally, presence of fluid in the SRNVM area, and the condition of the fellow eye.},
}

Humans
*Tomography, Optical Coherence/methods
Female
Male
*Retinal Neovascularization/diagnosis/etiology
Diagnosis, Differential
Fluorescein Angiography/methods
Aged
*Choroid/pathology/diagnostic imaging
Retinal Pigment Epithelium/pathology/diagnostic imaging
Middle Aged
*Optic Disk/pathology

@article {pmid42599645,
year = {2026},
author = {Salvatore, S and Harvey, J and Hughes, A and Gibson, L and Hopcroft, J and Swift, S and Marsterson, J and Bailey, C},
title = {Enhanced Macular Imaging Referral Pathway: Bridging Community Optometrists and Hospital Specialists for Smarter Eye Care.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42599645},
issn = {2193-8245},
abstract = {INTRODUCTION: Hospital eye services in England face sustained demand, with nearly 9 million outpatient appointments in 2023-2024. Teleophthalmology pathways that combine community-acquired imaging with hospital virtual review may reduce unnecessary face-to-face visits. We evaluated an enhanced macular imaging referral pathway linking community optometry optical coherence tomography (OCT) and colour fundus imaging with hospital-led teleophthalmology review.

METHODS: We performed a retrospective service evaluation of 376 consecutive adult macular referrals received at University Hospitals of Bristol and Weston, between July 2024 and March 2025. Community optometrists submitted bilateral macula-centred 45° colour fundus photographs, bilateral OCT volume scans in digital imaging and communications in medicine (DICOM) format and clinical data via a secure platform. Referrals were reviewed by a consultant ophthalmologist or hospital optometrist within 1 working day. Under the previous pathway, all accepted referrals required an initial face-to-face hospital appointment. Primary outcomes were referral appropriateness, avoided hospital appointments and redirection to other sub-specialties; secondary outcomes were management decision and diagnostic category. Analyses were descriptive.

RESULTS: Median age was 74 years (IQR 14); 54.3% were female. Overall, 327/376 referrals (87.0%, 95% CI 83.2-90.0) were appropriate for macular assessment. Of the referrals, 49 (13.0%) were inappropriate because of incomplete imaging (n = 18, 4.7%) or redirection to another sub-specialty (n = 31, 8.2%), most commonly vitreoretinal services (n = 27, 7.2%). Among appropriate referrals, 241/327 (73.7%, 95% CI 68.7-78.2) avoided the mandatory first hospital visit required under the previous pathway. Management outcomes across the cohort were: neovascular age-related macular degeneration (nAMD) pathway, 17.1%; redirection, 6.1%; discharge to community, 10.2%; virtual follow-up, 15.3%; and face-to-face appointment, 51.2%. Mean time to treatment for nAMD was 8.6 days (95% CI 6.0-11.2 days).

CONCLUSIONS: This teleophthalmology-enabled macular referral pathway achieved high referral appropriateness and substantially reduced mandatory first-visit hospital appointments while supporting timely treatment for sight-threatening macular disease. The model appears scalable and may help National Health Service hospital eye services manage rising demand more efficiently.},
}

@article {pmid42600888,
year = {2026},
author = {Huang, A and Ling, J and Gilead, N and Sherif, M and Teo, K and Lam, WC and Cheung, CMG},
title = {Variations in nAMD and PCV Phenotypes and Treatment Outcomes Across Singaporean, Canadian Asian, and Canadian Caucasian Populations.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.018},
pmid = {42600888},
issn = {1879-1891},
abstract = {PURPOSE: To compare the frequency of polypoidal choroidal vasculopathy (PCV) features, treatment patterns, and one-year outcomes across Singaporean Asian, Canadian Asian, and Canadian Caucasian populations with neovascular age-related macular degeneration (nAMD) using optical coherence tomography (OCT)-based diagnostic criteria.

DESIGN: Retrospective, multicenter, comparative study.

PARTICIPANTS: A total of 327 treatment-naïve patients with nAMD: 181 from Singapore National Eye Centre and 146 from Vancouver, Canada (89 Caucasian, 57 Asian).

METHODS: PCV was diagnosed using modified Asia-Pacific Ocular Imaging Society non-indocyanine green angiography OCT-based criteria (sharp-peaked pigment epithelial detachment and sub-retinal pigment epithelium ring-like lesion). Baseline OCT features, treatment patterns, and 12-month outcomes were compared across the three ethnic groups.

MAIN OUTCOME MEASURES: PCV prevalence, OCT-based morphological features, treatment patterns, and change in best-corrected visual acuity (BCVA) at 12 months.

RESULTS: PCV prevalence was similar between Singaporean Asian (42.5%) and Canadian Asian (42.1%) groups, both significantly higher than Canadian Caucasians (13.5%, P<0.01). OCT features in PCV eyes were consistent across ethnic groups, including macular predominance (79.2-83.3%), double-layer sign (83.3-93.5%), low soft drusen prevalence (4.2-8.3%), and subfoveal choroidal thickness >200 µm. Treatment patterns differed: bevacizumab predominated in Canada (65.0-70.0% for PCV), while Singapore used varied agents with photodynamic therapy in 31.1%. At 12 months, BCVA improved in Singaporean PCV eyes (-0.22 logMAR, P<0.01). In typical nAMD, BCVA improved significantly across all three groups.

CONCLUSIONS: Ethnic differences in PCV prevalence persist regardless of geographic location, supporting a predominant genetic basis for PCV susceptibility. OCT-based PCV features are consistent across ethnicities, while treatment patterns vary substantially between healthcare systems. Non-invasive OCT-based diagnostic criteria enable reliable cross-ethnic PCV comparison when indocyanine green angiography is unavailable.},
}

@article {pmid42601611,
year = {2026},
author = {Lin, Y and Zhang, X and Huang, Z and Ye, Y and Yan, M and Song, Y},
title = {Predictors of 1-year fibrosis in treatment-naïve neovascular age-related macular degeneration: the role of baseline OCTA-derived MNV vessel density.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42601611},
issn = {1471-2415},
support = {2025BSH070//the Postdoctoral Scientific Research Foundation, General Hospital of Central Theater Command/ ; 82471110//the National Natural Science Foundation of China General Program/ ; },
mesh = {Humans ; Retrospective Studies ; *Tomography, Optical Coherence/methods ; Fibrosis/diagnosis ; Fluorescein Angiography/methods ; Angiogenesis Inhibitors/therapeutic use ; Female ; Male ; *Wet Macular Degeneration/drug therapy/diagnosis/pathology ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; Intravitreal Injections ; Visual Acuity ; Follow-Up Studies ; Fundus Oculi ; Aged, 80 and over ; ROC Curve ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Macula Lutea/pathology ; },
abstract = {BACKGROUND: To investigate baseline and post-loading optical coherence tomography angiography (OCTA) characteristics associated with 1-year fibrosis in treatment-naïve neovascular age-related macular degeneration (nAMD), and to evaluate whether baseline clinical variables combined with OCTA-derived biomarkers could improve fibrosis prediction.

METHODS: This retrospective, single-center study included treatment-naïve nAMD eyes with type 1 or type 2 macular neovascularization (MNV) that completed a 3 + PRN anti-VEGF loading regimen and had at least 12 months of follow-up. High-quality OCTA images were required at baseline and at the post-loading visit, defined as within 1 week after completion of the three-injection anti-VEGF loading phase. OCTA quantitative parameters, including fractal dimension, branch points, endpoints, segments, and MNV vessel density, were measured within the manually delineated MNV region of interest. Baseline clinical and imaging characteristics were compared between fibrosis and non-fibrosis groups. Univariate and multivariable logistic regression analyses were performed to identify factors associated with 1-year fibrosis, and receiver operating characteristic (ROC) curves were used to assess predictive performance.

RESULTS: A total of 72 patients (88 eyes) were included, of which 31 eyes developed fibrosis at 1 year and 57 did not. Compared with the non-fibrosis group, eyes that developed fibrosis had worse baseline best-corrected visual acuity (BCVA), greater baseline central macular thickness (CMT), and a higher prevalence of subretinal hyperreflective material (SHRM), retinal hemorrhage, type 2/mixed MNV, high pigment epithelial detachment, and intraretinal fluid. At baseline, the fibrosis group showed significantly higher MNV vessel density, whereas MNV fractal dimension showed a borderline difference. At the post-loading visit, MNV fractal dimension, MNV branch points, MNV endpoints, MNV segments, and MNV vessel density were all significantly higher in the fibrosis group. However, within-group comparisons between baseline and the post-loading visit revealed no significant changes in OCTA parameters in either group. In multivariable analysis, baseline BCVA (OR 1.162, 95% CI 1.024-1.319; P = 0.020), baseline CMT (OR 1.032, 95% CI 1.001-1.064; P = 0.043), and baseline MNV vessel density (OR 1.073, 95% CI 1.009-1.142; P = 0.025) remained independently associated with 1-year fibrosis, whereas SHRM did not. The combined model achieved the best predictive performance, with an area under the ROC curve of 0.787 (95% CI 0.688-0.874).

CONCLUSIONS: Eyes with treatment-naïve nAMD that developed fibrosis within 1 year had worse baseline disease status and distinct OCTA microvascular characteristics. Baseline BCVA, baseline CMT, and baseline MNV vessel density were independently associated with fibrosis. Integrating conventional clinical and structural features with OCTA-derived MNV vessel density may provide complementary information for fibrosis risk stratification in nAMD.},
}

Humans
Retrospective Studies
*Tomography, Optical Coherence/methods
Fibrosis/diagnosis
Fluorescein Angiography/methods
Angiogenesis Inhibitors/therapeutic use
Female
Male
*Wet Macular Degeneration/drug therapy/diagnosis/pathology
*Retinal Vessels/pathology/diagnostic imaging
Aged
Intravitreal Injections
Visual Acuity
Follow-Up Studies
Fundus Oculi
Aged, 80 and over
ROC Curve
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Macula Lutea/pathology

@article {pmid42598505,
year = {2026},
author = {Alibrandi, S and Mordà, D 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 = {Quantum molecular resonance and secretome synergistically unlocks a protective ceRNA axis in the human retinal pigment epithelium.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {3},
pages = {103034},
pmid = {42598505},
issn = {2162-2531},
abstract = {The retinal pigment epithelium (RPE) contributes to retinal homeostasis in part through non-coding RNA (ncRNA) regulatory networks, and its degeneration underlies blinding diseases. How physical and paracrine regenerative stimuli affect the RPE non-coding transcriptome remains unknown. We performed RNA-seq on ARPE-19 cells in a full-factorial design of four treatments (CTRL, QMR, a patient blood-derived secretome, and QMR+SECRETOME) two oxidative-stress states (basal and tert-butyl hydroperoxide [tBHP]-induced), and three time points (8, 24, 72 h). lncRNAs and circRNAs were sub-classified and mapped via GO enrichment and in silico ceRNA prediction. PCA identified QMR as the dominant driver of transcriptomic variance, priming ARPE-19 cells to integrate paracrine signals. Analysis across six factorial contrasts identified 105 modulated non-coding transcripts, including a pan-responsive antisense core (BASP1-AS1, SOD2-OT1) and condition-specific shifts in master lincRNAs (NEAT1, MALAT1). QMR+SECRETOME produced a distinct combinatorial transcriptomic signature. circASPH was exclusively upregulated by QMR, while circCRIM1 was preferentially hyperactivated by combinatorial treatment. ceRNA analysis predicted potential sponging of miR-29, miR-21, and miR-155, which may derepress BMP signaling and extracellular matrix remodeling. QMR reshapes the ARPE-19 non-coding transcriptome and enables a non-additive transcriptomic response to secretome co-treatment. The QMR-secretome-circRNA axis identifies candidate non-coding biomarkers and therapeutic targets for retinal regeneration.},
}

@article {pmid42598632,
year = {2026},
author = {Chen, KM and Chen, KW and Patil, A and Diaconita, V and Chang, S and Suh, LH},
title = {OphthoChat: A HIPAA-Compliant, Artificial Intelligence-Driven Natural-Language Chatbot for Ophthalmic Electronic Medical Record Querying and Analysis.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101315},
pmid = {42598632},
issn = {2666-9145},
abstract = {PURPOSE: To introduce and evaluate OphthoChat, a Health Insurance Portability and Accountability Act-compliant, artificial intelligence (AI)‑powered natural language chatbot designed to enable clinicians to query ophthalmic electronic medical records (EMRs) using conversational language, without requiring coding experience.

DESIGN: Retrospective validation study using a clinical data set and clinician-authored queries.

PARTICIPANTS: The study included 500 adult patients seen at Columbia University Irving Medical Center between 2020 and 2025: 250 patients who received intravitreal injections for wet age-related macular degeneration and 250 patients who underwent cataract surgery.

METHODS: We processed >50 000 EMR artifacts, including progress notes, operative reports, imaging summaries, and optical character recognition‑converted scanned documents, into a vectorized database. OphthoChat used a retrieval-augmented generation architecture powered by GPT-4o to answer 1000 natural-language queries stratified by complexity (simple, intermediate, advanced). Each response was evaluated against a reference standard determined by dual clinician adjudication.

MAIN OUTCOME MEASURES: Primary metrics included response accuracy, sensitivity, specificity, and time-to-answer per query. Supporting chart citations were also assessed for traceability and rank.

RESULTS: OphthoChat achieved an overall accuracy of 96%, with a sensitivity of 93% and a specificity of 97%. Median time to answer a query was 35 seconds, an 11-fold speed improvement over manual chart review (6.6 minutes). Among correct responses, 97% of cited lines matched the reference standard, with a mean reciprocal rank of 0.92. Performance remained strong across all difficulty levels, including 91% accuracy on advanced narrative inference tasks. The system demonstrated robustness in processing complex chart histories while offering full traceability.

CONCLUSIONS: OphthoChat enables fast, accurate, and traceable chart review in ophthalmology through natural-language dialogue. By eliminating the need for technical setup or programming knowledge, it significantly lowers the barrier to AI adoption in clinical research and practice. OphthoChat's ability to synthesize complex EMR data across structured and unstructured formats offers a scalable solution for accelerating outcomes research, clinical decision-making, and cohort identification. Further development will focus on EMR integration and subspecialty expansion.

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

@article {pmid42599028,
year = {2026},
author = {Zhao, H and Gao, B and Ding, N and Zhang, R and Zhou, W and Song, G and Li, H and Wu, H and Yang, Y and Shao, L and Dong, L and Wei, W},
title = {Aqueous Humor Proteomics Reveals the Molecular Basis for Differential Treatment Responses in nAMD and pmCNV.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {36},
doi = {10.1167/iovs.67.10.36},
pmid = {42599028},
issn = {1552-5783},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Proteomics/methods ; Female ; Biomarkers/metabolism ; *Choroidal Neovascularization/metabolism/drug therapy ; Male ; *Wet Macular Degeneration/metabolism/drug therapy ; Aged ; *Eye Proteins/metabolism ; Angiogenesis Inhibitors/therapeutic use ; *Myopia/metabolism/complications ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Mass Spectrometry ; },
abstract = {PURPOSE: Choroidal neovascularization (CNV) causes vision loss in neovascular age-related macular degeneration (nAMD) and pathologic myopia-related CNV (pmCNV). Despite shared clinical features, they respond differently to treatment. This study compared aqueous humor (AH) proteomic profiles of nAMD and pmCNV to identify biomarkers and mechanisms of CNV formation.

METHODS: AH samples were collected from eyes with nAMD, pmCNV, age-related cataract controls, and pathologic myopia without CNV. Label-free data-independent acquisition (DIA) mass spectrometry was used for proteomic profiling. Differentially expressed proteins were identified using limma models adjusted for age, sex, and axial length. Functional enrichment analyses used Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome databases. Stability-based feature selection, LightGBM modeling, and SHapley Additive exPlanations (SHAP) prioritized discriminative proteins; selected findings were evaluated in an independent nAMD-control Olink cohort.

RESULTS: DIA proteomics identified 3986 proteins, of which 3667 passed quality filtering. nAMD and pmCNV showed weakly correlated proteomic alterations (r2 = 0.061), with 385 nAMD-specific, 398 pmCNV-specific, and 100 shared altered proteins. nAMD was characterized by vascular endothelial growth factor (VEGF/VEGF receptor [VEGFR]) pathway activation and reduced glucose-metabolism-related proteins, whereas pmCNV showed extracellular matrix remodeling, platelet/coagulation activation, and downregulation of Slit/Robo-related neurovascular guidance pathways. The stability-selected LightGBM model using 33 proteins achieved a macro-average area under the curve (AUC) of 0.92. SHAP analysis highlighted VEGFR2 (KDR) and VEGFA as major nAMD-associated drivers, and Olink validation showed concordant expression trends for six selected proteins.

CONCLUSIONS: nAMD and pmCNV exhibit largely distinct AH proteomic signatures, supporting different molecular mechanisms of CNV formation and anti-VEGF responsiveness. AH proteomics may help prioritize subtype-specific candidate biomarkers, warranting further validation across independent cohorts.},
}

Humans
*Aqueous Humor/metabolism
*Proteomics/methods
Female
Biomarkers/metabolism
*Choroidal Neovascularization/metabolism/drug therapy
Male
*Wet Macular Degeneration/metabolism/drug therapy
Aged
*Eye Proteins/metabolism
Angiogenesis Inhibitors/therapeutic use
*Myopia/metabolism/complications
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Mass Spectrometry

@article {pmid42599042,
year = {2026},
author = {Veernala, I and Chan, KS and Congivaram, HTS and Cuamatzi-Castelan, AS and Rajesh, A and Gong, J and Ide, OC and Lavine, JA and , },
title = {The Role of Dopaminergic Agonists in Geographic Atrophy: Converging Evidence From Clinical and Experimental Data.},
journal = {Translational vision science & technology},
volume = {15},
number = {8},
pages = {10},
doi = {10.1167/tvst.15.8.10},
pmid = {42599042},
issn = {2164-2591},
mesh = {Animals ; Mice ; *Geographic Atrophy/drug therapy/pathology/chemically induced ; *Levodopa/therapeutic use/pharmacology ; Retrospective Studies ; *Dopamine Agonists/therapeutic use/pharmacology ; Humans ; Male ; Disease Models, Animal ; Tomography, Optical Coherence ; Female ; Mice, Inbred C57BL ; Retinal Pigment Epithelium/pathology/drug effects ; Aged ; Receptors, Dopamine D2/agonists ; },
abstract = {PURPOSE: Levodopa (L-DOPA) is an emerging drug repurposing candidate for age-related macular degeneration (AMD). Basic and clinical studies identify a potential role for L-DOPA to prevent and treat neovascular AMD. However, only one prior study has been performed in geographic atrophy (GA).

METHODS: We performed a retrospective cohort analysis from the Sight Outcomes Research Collaborative database, including eyes with a diagnosis of early- or intermediate-stage AMD in 1 eye. We compared eyes exposed to any dopamine agonist (DA), dopamine receptor D2 agonist, and L-DOPA with eyes with no DA exposure using propensity score matching and survival analysis with multivariable Cox proportional hazard models with new GA development as our primary outcome. Mice were treated with intraperitoneal NaIO3 to induce GA-like pathology. We compared L-DOPA with phosphate-buffered saline-treated controls in both pigmented and albino mice. We quantified retinal thickness by optical coherence tomography, and performed immunofluorescence to quantify choriocapillaris and retinal pigment epithelium density.

RESULTS: Any DA, dopamine receptor D2, and L-DOPA exposure were not associated with new-onset GA. NaIO3 treatment caused retinal thinning, choriocapillaris loss, and retinal pigment epithelium degeneration, which were not rescued by L-DOPA treatment in pigmented nor albino mice.

CONCLUSIONS: In both retrospective database analysis and preclinical models, DA had no effect upon GA pathology.

TRANSLATIONAL RELEVANCE: Further investigation of levodopa may be more appropriately directed toward neovascular age-related macular degeneration, rather than geographic atrophy, where preclinical, retrospective, epidemiologic, and prospective data suggest a benefit.},
}

Animals
Mice
*Geographic Atrophy/drug therapy/pathology/chemically induced
*Levodopa/therapeutic use/pharmacology
Retrospective Studies
*Dopamine Agonists/therapeutic use/pharmacology
Humans
Male
Disease Models, Animal
Tomography, Optical Coherence
Female
Mice, Inbred C57BL
Retinal Pigment Epithelium/pathology/drug effects
Aged
Receptors, Dopamine D2/agonists

@article {pmid42592127,
year = {2026},
author = {Wei, Y and Zhao, K and Grzybowski, A and Jin, K},
title = {Federated learning for privacy-preserving ophthalmic artificial intelligence: clinical applications and translational challenges.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1904004},
pmid = {42592127},
issn = {2296-858X},
abstract = {Federated learning (FL) is increasingly relevant to ophthalmology because retinal photographs, optical coherence tomography (OCT), OCT angiography, visual fields, and linked clinical records are clinically valuable but difficult to pool across institutions. In this narrative review, we synthesize ophthalmology-focused FL literature across diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), pediatric retinal disease, multi-disease retinal diagnostics, and emerging ophthalmic platforms. Current evidence suggests that FL can support collaborative AI development without centralizing raw patient data, and selected studies show performance close to centralized training under controlled retrospective or multicenter experimental conditions. For example, multicenter glaucoma detection from volumetric OCT achieved an AUC of 0.92 with FL compared with 0.94 for centralized training. However, FL is privacy-enhancing rather than privacy-complete, and most ophthalmic FL systems have not yet undergone prospective clinical validation. Model updates may remain vulnerable to gradient inversion, membership inference, poisoning, site-level bias, and latent identity or attribute leakage. For eye-care networks, the main value of FL is therefore not simply algorithmic performance but a governance model for privacy-conscious collaboration. Prospective validation, interoperability, explainability, workflow integration, privacy auditing, and clear responsibility for monitoring are needed before FL-enabled ophthalmic AI can be deployed routinely.},
}

@article {pmid42593178,
year = {2026},
author = {Zhu, M and Cui, L and Guo, Y and Tu, Y and Wang, Y and Zhou, W and Zhang, Y and Xie, L and Jin, H},
title = {LPA1-Induced EMT of Retinal Pigment Epithelial Cells Promotes Subretinal Fibrosis via USP1-Mediated Deubiquitination and Stabilization of ZEB1.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {34},
doi = {10.1167/iovs.67.10.34},
pmid = {42593178},
issn = {1552-5783},
mesh = {Animals ; *Zinc Finger E-box-Binding Homeobox 1/metabolism/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; Mice ; Fibrosis/metabolism ; *Epithelial-Mesenchymal Transition/physiology ; Mice, Inbred C57BL ; Blotting, Western ; Disease Models, Animal ; Ubiquitination ; *Ubiquitin-Specific Proteases/metabolism ; Cells, Cultured ; Cell Movement ; *Gene Expression Regulation ; },
abstract = {PURPOSE: Subretinal fibrosis (SRF) is a vision-threatening complication of neovascular age-related macular degeneration (nAMD), yet effective antifibrotic strategies remain limited. This study investigated the role of lysophosphatidic acid receptor 1 (LPA1), a fibrosis-associated G protein-coupled receptor, in SRF progression and evaluated its therapeutic potential.

METHODS: A two-stage laser injury model was used to induce SRF in C57BL/6J mice. LPA1 expression and its regulation of ubiquitin-specific peptidase 1 (USP1) and zinc finger E-box binding homeobox 1 (ZEB1) were assessed by western blotting and immunofluorescence. Retinal pigment epithelial (RPE) cell epithelial-mesenchymal transition (EMT) was evaluated by migration assays and fibrotic marker analysis. ZEB1 and USP1 loss-of-function experiments were performed to define their roles. Molecular docking and co-immunoprecipitation were used to examine USP1-mediated ZEB1 deubiquitination. The antifibrotic effects and the safety of LPA1 inhibition by BMS-986278 were assessed in vivo.

RESULTS: LPA1 was upregulated in laser-induced SRF and was associated with increased fibrotic marker expression. LPA1 overexpression promoted RPE EMT and migration through the USP1/ZEB1 axis. Mechanistically, LPA1 increased USP1 expression, which stabilized ZEB1 and promoted its nuclear translocation by reducing ZEB1 ubiquitination. USP1 inhibition attenuated LPA1-induced EMT and fibrosis, similar to ZEB1 silencing. In vivo, BMS-986278 suppressed EMT and reduced SRF severity, with a stronger inhibitory effect on fibrotic lesions than on neovascular lesions.

CONCLUSIONS: LPA1 promotes SRF by driving RPE EMT through USP1-mediated deubiquitination and stabilization of ZEB1. Targeting the LPA1/USP1/ZEB1 axis may provide a promising therapeutic strategy for nAMD-associated SRF.},
}

Animals
*Zinc Finger E-box-Binding Homeobox 1/metabolism/genetics
*Retinal Pigment Epithelium/metabolism/pathology
Mice
Fibrosis/metabolism
*Epithelial-Mesenchymal Transition/physiology
Mice, Inbred C57BL
Blotting, Western
Disease Models, Animal
Ubiquitination
*Ubiquitin-Specific Proteases/metabolism
Cells, Cultured
Cell Movement
*Gene Expression Regulation

@article {pmid42593483,
year = {2026},
author = {Reiter, GS and Loewenstein, A},
title = {Enriched trial designs and the patients left behind.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42593483},
issn = {1435-702X},
}

@article {pmid42593648,
year = {2026},
author = {Baker, L and Rahhal, FM and Gilbert, CJ and Leng, T},
title = {Understanding the Geographic Atrophy Journey: Patient and Physician Perspectives to Inform Better Care.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42593648},
issn = {2193-8245},
support = {P30-EY026877/EY/NEI NIH HHS/United States ; },
abstract = {OBJECTIVES: Geographic atrophy (GA) can place substantial physical and emotional burdens on affected individuals, related to both the disease and its treatment. Here, we provide insights into the perspectives of a patient with GA and retina specialists around GA diagnosis, treatment, communication, and needs.

METHODS: Unstructured qualitative interviews were conducted with a patient author with GA and two retina specialist authors involved in the management of GA. The authors discussed early GA symptoms, its diagnosis and management, treatment experience, support, and education.

RESULTS: Several themes emerged. A GA diagnosis can be emotionally distressing and difficult for patients to accept. The reality is that although current treatments delay progression of further visual impairments, these therapies do not restore lost vision. Current GA treatments are associated with frequent clinic visits and intravitreal injections that can lead to discomfort and temporary visual disturbances, which are disruptive to daily life. Physicians also noted a lack of clinical endpoints for guiding optimal dosing. The importance of patient-physician communication in the management of GA was highlighted, focusing on an approach that incorporates the emotional and practical needs of patients. Physicians play a central role in ensuring treatment compliance to minimize further vision loss. Peer support is also invaluable for sharing experiences, treatment expectations, and reassurance. Finally, patient and provider suggestions for improving outcomes for people with GA were discussed, including access to patient-focused educational materials on GA and treatment, development of tangible endpoints in clinical trials, and facilitation of peer support. All authors supported the development of long-acting formulations, systemic medications, or optimally a cure, to reduce treatment burden.

CONCLUSIONS: GA and its treatment place a substantial burden on patients. Multiple opportunities remain to improve the experiences of people with GA and empower patients to understand their condition and treatment, which ultimately could improve their outcomes. Audio feature available for this article.},
}

@article {pmid42593649,
year = {2026},
author = {Angers, S and Wykoff, CC and Antonetti, DA and Junge, HJ and Nudleman, E and Nagiel, A and Schlottmann, PG and D'Amico, DJ and Prenner, J and Guyer, DR and Miller, CG and Baker, K and Stephens, P and Henry, E and Rekers, H and Adamis, AP and Ng, YSE},
title = {Wnt Pathway Agonism as a Therapeutic Strategy for Retinal Vascular Diseases: A Narrative Review of Evidence to Date.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42593649},
issn = {2193-8245},
abstract = {Breakdown of the blood-retinal barrier (BRB) is implicated in many blinding retinal diseases, including diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion. Anti-vascular endothelial growth factor (anti-VEGF) therapies or laser photocoagulation are currently the standard of care for retinal diseases that are characterized by breakdown of the vascular barrier function and vascular hyperpermeability. However, inadequate response to anti-VEGF therapy is seen in a substantial proportion of patients and laser photocoagulation does not restore vision loss and can lead to collateral damage of the retina. Thus, new therapeutic targets are needed. The β-catenin-dependent wingless-related integration site (Wnt) signaling pathway plays a critical role in inner BRB development and maintenance. There are several potential therapeutics for retinal vascular diseases targeting the Wnt/β-catenin pathway under investigation, including several in preclinical development and one (MK-3000; also known as Restoret and formerly EYE103) with early clinical trial results advancing to late-stage clinical development. In this narrative review we examine the role of Wnt/β-catenin signaling in inner BRB maintenance and in retinal vascular diseases, as well as the potential for Wnt pathway agonism as a therapeutic approach.},
}

@article {pmid42594967,
year = {2026},
author = {Ferrara, S and Schloss, J},
title = {Does Crocus sativus (Saffron) Have an Influence or Effect on Ocular Health: A Systematic Literature Review.},
journal = {Journal of evidence-based integrative medicine},
volume = {31},
number = {},
pages = {2515690X261478846},
doi = {10.1177/2515690X261478846},
pmid = {42594967},
issn = {2515-690X},
mesh = {*Crocus/chemistry ; Humans ; Vitamin A/analogs & derivatives ; Carotenoids/pharmacology ; *Eye Diseases/drug therapy ; *Plant Extracts/pharmacology ; },
abstract = {BackgroundCrocus sativus (Saffron) and its bioactive constituents, crocin and crocetin have gained attention for their neuroprotective and antioxidant properties in ocular health. This review synthesises clinical evidence from extracted studies evaluating their efficacy, safety and dosing across Age-related Macular Degeneration (AMD), Primary Open-Angle Glaucoma (POAG), Diabetic Macular Edema (DME), Central Serous Retinopathy (CSR), Stargardt Disease (STGD1) and Paediatric Myopia (PM).MethodologyA systematic literature review was undertaken assessing randomized trials, observational or cohort studies, case studies or series written in English between January 2015 to January 2025. Studies were identified using PubMed, AMED, CINHAL, ScienceDirect and Scopus as well as the grey literature.ResultsTen clinical trials were identified from 529 citations. Interventions involved oral supplementation of saffron (20-50mg/day), crocin (5-15mg/day) and crocetin (7.5mg/day) over durations ranging from 6 weeks to 12 months. Primary outcomes included visual acuity, retinal electrophysiology, intra-ocular pressure, macular thickness, and safety profiles.ConclusionSaffron, crocin and crocetin, demonstrate consistent efficacy and exceptional safety profiles across a range of ocular conditions. Saffron's dose-dependent therapeutic effects are a promising adjunctive therapy in ophthalmology. Further large-scale trials are warranted to confirm these findings and refine condition specific dosing.},
}

*Crocus/chemistry
Humans
Vitamin A/analogs & derivatives
Carotenoids/pharmacology
*Eye Diseases/drug therapy
*Plant Extracts/pharmacology

@article {pmid42597498,
year = {2026},
author = {Miller, WP and Arevalo-Alquichire, S and Perez-Corredor, P and Lin, R and Upreti, A and Sanchez-Suarez, J and Vanderleest, TE and Marino, C and Spencer, D and Scribner, M and Vargas, J and Muriel-Torres, A and Hu, X and Adu-Rutledge, Y and Kaplan, BA and Barake, KW and Gunawan, AL and Vijikumar, A and Shrestha, R and Lennikov, A and Kim, LA and Arboleda-Velasquez, JF and Peterson, A and Agrawal, S and Vathipadiekal, V and Loya, C and O'Hare, M},
title = {Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {3},
pages = {103024},
pmid = {42597498},
issn = {2162-2531},
abstract = {Antisense oligonucleotides (ASOs) are RNA-targeting therapeutics with broad potential for genetically defined and complex ocular diseases. The eye is particularly well suited for ASO delivery because of its compartmentalized anatomy, accessibility, and capacity for sustained intraocular drug retention. Autosomal dominant drusen (ADD), an inherited retinal dystrophy characterized by early drusen formation and secondary choroidal neovascularization (CNV), is caused by the EFEMP1 R345W mutation. Mutant EFEMP1 accumulates within the retinal pigment epithelium (RPE) and extracellular matrix, contributing to disease pathology. EFEMP1 is also elevated in the serum and RPE/choroid of patients with age-related macular degeneration (AMD), although its functional role in AMD remains incompletely defined. Here, we developed a biallelic EFEMP1-targeted ASO that achieved potent knockdown and modulated disease-relevant pathways in iPSC-derived RPE, human microvascular retinal endothelial cells (HMRECs), ex vivo human choroidal explants, and in vivo mouse models. EFEMP1 protein levels were increased in AMD tissue, and ASO-mediated EFEMP1 knockdown reduced complement factor 3 (C3), suppressed HMREC proliferation and migration, and inhibited angiogenic sprouting in choroidal explants. These findings support EFEMP1 as a pathogenic regulator of retinal degeneration and vascular dysfunction and establish EFEMP1-directed ASOs as a promising therapeutic strategy for ADD and AMD.},
}

@article {pmid42598009,
year = {2026},
author = {Abdalla Elsayed, MEA and MacLaren, RE},
title = {Quantification of Ocular Gene Therapy-Related Inflammation Using the VRMACS Grading System.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101316},
pmid = {42598009},
issn = {2666-9145},
abstract = {Retinal gene therapy has been shown to be a benefit in treating inherited retinal degenerations and may become the first line of treatment for patients with more common conditions such as age-related macular degeneration and diabetic retinopathy. A major limitation of ocular gene therapy is inflammation which has occurred in several clinical trials and may be the cause of dose limiting toxicity. Up until now it is been difficult to grade inflammation due to the small number of studies across many different centers. The absence of a standardized, reproducible system to grade retinal inflammation limits cross-study comparisons and consistent safety assessment. We synthesize evidence from published retinal gene therapy studies that report inflammatory outcomes and from our gene therapy center. Based on these findings, we propose a standardized grading framework-the vitritis, retinitis, microperimetry changes, fundus autofluorescence abnormalities, choroiditis, and subretinal infiltrates (VRMACS) score-to assess retinal inflammation over time using clinical examination and multimodal imaging. The system evaluates 6 domains: vitritis, retinitis, microperimetry changes, fundus autofluorescence abnormalities, choroiditis, and subretinal infiltrates. Grading allows for structured, longitudinal assessment of inflammatory severity after gene therapy. The VRMACS score provides a standardized grading system that may improve detection, quantification, and reporting of inflammation associated with subretinal ocular gene therapy. Standardized inflammation grading could support dose selection, guide prespecified stopping rules, and improve consistency in the interpretation of inflammation-related adverse events across early- and late-phase trials. From a regulatory perspective, adoption of this system may support consistent safety assessment across clinical trials and facilitate regulatory evaluation of inflammation-related adverse events. Clinically, VRMACS offers a practical tool for monitoring patients receiving retinal gene therapy and guiding timely intervention.},
}

@article {pmid42598079,
year = {2026},
author = {Gui, C and Chen, X and Liu, H and Dong, J and Zhang, Q and Gao, Y and Peng, Q},
title = {Dynamic changes in aqueous humor cytokines and OCTA parameters during aflibercept loading in treatment-naive neovascular age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1857826},
pmid = {42598079},
issn = {2296-858X},
abstract = {PURPOSE: To investigate dynamic changes in aqueous humor cytokines and retinal vessel density during aflibercept loading in treatment-naive neovascular age-related macular degeneration (nAMD), and to analyze their associations with visual improvement.

METHODS: This single-center retrospective clinical study included 20 treatment-naive patients with nAMD (20 eyes) and 20 patients with cataracts (20 eyes). In the nAMD group, aqueous humor samples were collected at baseline and at the time of the third intravitreal aflibercept injection, while samples from the cataract control group were obtained before surgery. Relevant aqueous humor cytokines were measured using the Bio-Plex suspension bead array system. In the nAMD group, best-corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA) examinations were performed at baseline and at 1 and 2 months after treatment. Longitudinal changes in OCTA parameters were analyzed using mixed-effects models, followed by correlation analyses. According to the final BCVA outcome, eyes in the nAMD group were further classified into an obvious-improvement group and a non-obvious-improvement group for exploratory subgroup comparison.

RESULTS: Compared with the cataract control group, eyes with nAMD showed significant differences in baseline aqueous humor levels of Ang-2, HGF, VEGF-C, IP-10, HB-EGF, IL-8, and PlGF. During aflibercept loading, aqueous humor levels of Ang-2, HGF, and IP-10 increased, whereas IL-8 decreased. At month 2, the superficial parafoveal vessel density and the superficial and deep perifoveal vessel density decreased significantly compared with baseline, while BCVA improved significantly. Baseline Ang-2, bFGF, and IL-8 showed nominal exploratory associations with OCTA changes, but these associations did not remain significant after FDR correction. In subgroup analysis of the nAMD cohort, only the change in deep perifoveal vessel density differed significantly between the obvious-improvement group and the non-obvious-improvement group.

CONCLUSION: Treatment-naive nAMD eyes exhibited differential changes in aqueous humor cytokines during aflibercept loading, consistent with possible non-VEGF pathway involvement. Meanwhile, regional remodeling of retinal microcirculation was observed, and changes in deep perifoveal vessel density showed a trend consistent with short-term visual improvement.},
}

@article {pmid42582531,
year = {2026},
author = {Narapareddy, M and Balakrishnan, N and Iqbal, MA},
title = {Retinal Pigment Epithelial Detachment Following Topical Travoprost Therapy.},
journal = {Journal of current glaucoma practice},
volume = {20},
number = {2},
pages = {102-105},
pmid = {42582531},
issn = {0974-0333},
abstract = {Prostaglandin analogs, including travoprost, are widely used to lower intraocular pressure in primary open-angle glaucoma. While generally safe, rare posterior segment changes have been reported. Retinal pigment epithelial detachment (RPED) associated with travoprost is uncommon and poorly documented. We report three patients who developed serous RPED shortly after initiating topical travoprost, none of whom had preexisting macular disease. Optical coherence tomography (OCT) confirmed the detachments, and complete anatomical and visual recovery occurred following discontinuation of travoprost and initiation of alternative glaucoma therapy. A clear temporal relationship was observed between drug initiation and RPED onset. The absence of clinical or OCT features suggestive of alternative diagnoses-such as central serous chorioretinopathy, age-related macular degeneration, or pachychoroid spectrum disorders-combined with consistent reversibility, suggests a possible association between travoprost and RPED. These findings emphasize the importance of early recognition and timely intervention, as RPED appears fully reversible when identified promptly, preventing potential persistent visual impairment.},
}

@article {pmid42584788,
year = {2026},
author = {Lu, Y and Reschigna, A and Kynast, F and Yang, Z and Gerhardt, M and Kielkowski, P and Priglinger, S and Biel, M and Michalakis, S},
title = {Lysosomal channel TPC2 modulates microglia-endothelial signaling in choroidal angiogenesis.},
journal = {Angiogenesis},
volume = {29},
number = {4},
pages = {},
pmid = {42584788},
issn = {1573-7209},
mesh = {Animals ; Two-Pore Channels ; Humans ; *Microglia/metabolism/pathology ; *Choroidal Neovascularization/metabolism/pathology/genetics ; *Lysosomes/metabolism ; *Signal Transduction ; *Calcium Channels/metabolism/genetics ; *Endothelial Cells/metabolism/pathology ; Mice ; Mice, Knockout ; },
abstract = {Pathological choroidal neovascularization underlies vision loss in neovascular age-related macular degeneration (nAMD), yet the molecular regulators coordinating vascular and immune components remain incompletely defined. Here, we investigated the role of the endolysosomal cation channel, two-pore channel 2 (TPC2) in choroidal angiogenesis. Loss of TPC2 in mice markedly reduced ex vivo choroidal sprouting, while pharmacological activation enhanced vascular growth. Mechanistically, Tpc2-deficiency led to downregulation of multiple microglia-derived pro-angiogenic factors and impaired the ability of the microglial secretome to stimulate neovascularization. In choroidal vascular cells, TPC2 loss attenuated NF-κB/MAPK signaling pathways. Tpc2-deficiency is also associated with lysosomal secretion of cathepsins, especially CTSD, resulting in decreased extracellular proteolytic activity and impaired paracrine regulation of angiogenesis. Extending these findings to human cells, TPC2 knockout in iPSC-derived endothelial cells impaired migration, tube formation, and CTSD activity in the secretome, mirroring the murine phenotype. Together, these results establish TPC2 as one of the regulators of lysosome-mediated choroidal angiogenesis, highlighting its potential as a therapeutic target in nAMD.},
}

Animals
Two-Pore Channels
Humans
*Microglia/metabolism/pathology
*Choroidal Neovascularization/metabolism/pathology/genetics
*Lysosomes/metabolism
*Signal Transduction
*Calcium Channels/metabolism/genetics
*Endothelial Cells/metabolism/pathology
Mice
Mice, Knockout

@article {pmid42585000,
year = {2026},
author = {Colasanti, JJ and Santeford, A and Lin, JB and Terao, R and Lee, TJ and Apte, RS},
title = {MicroRNA-34a suppresses KLF2 to promote pathological angiogenesis through the CXCR4/CXCL12 pathway in age-related macular degeneration.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {33},
pages = {e2524037123},
doi = {10.1073/pnas.2524037123},
pmid = {42585000},
issn = {1091-6490},
support = {EY019287//HHS | National Institutes of Health (NIH)/ ; EY02687//HHS | National Institutes of Health (NIH)/ ; 1T32GM197740-1//HHS | National Institutes of Health (NIH)/ ; F30DK130282//HHS | National Institutes of Health (NIH)/ ; T32GM07200//HHS | National Institutes of Health (NIH)/ ; },
mesh = {*MicroRNAs/genetics/metabolism ; Animals ; *Kruppel-Like Transcription Factors/metabolism/genetics ; *Macular Degeneration/genetics/metabolism/pathology ; Mice ; Humans ; *Choroidal Neovascularization/genetics/metabolism/pathology ; *Receptors, CXCR4/metabolism/genetics ; *Chemokine CXCL12/metabolism/genetics ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism/genetics ; Mice, Inbred C57BL ; Disease Models, Animal ; *Neovascularization, Pathologic/genetics/metabolism ; Male ; },
abstract = {Age-related macular degeneration (AMD), characterized by pathologic choroidal neovascularization (CNV), is a leading cause of vision loss in the elderly. Vascular endothelial growth factor A (VEGFa) antagonists can prevent acute vision loss, but high treatment burden and loss of efficacy with chronic therapy highlight the need to explore alternative mechanisms. Recently, microRNA-34a (miR-34a) has emerged as a key regulator in aging and age-related diseases, but its role in neovascular AMD is unclear. In an injury-induced murine CNV model, we found miR-34a promoted pathological angiogenesis, without altering expression of Vegfa or its receptor Kdr, the canonical regulators of CNV. Mechanistically, miR-34a directly targets and inhibits the transcription factor KLF2, thereby upregulating the proangiogenic factors CXCR4 and CXCL12. Finally, we show miR-34a exacerbates CNV in aged mice and is expressed in CNV lesions excised from wet AMD patients. These findings establish a causal link between the age-related miR-34a and neovascularization in AMD.},
}

*MicroRNAs/genetics/metabolism
Animals
*Kruppel-Like Transcription Factors/metabolism/genetics
*Macular Degeneration/genetics/metabolism/pathology
Mice
Humans
*Choroidal Neovascularization/genetics/metabolism/pathology
*Receptors, CXCR4/metabolism/genetics
*Chemokine CXCL12/metabolism/genetics
Signal Transduction
Vascular Endothelial Growth Factor A/metabolism/genetics
Mice, Inbred C57BL
Disease Models, Animal
*Neovascularization, Pathologic/genetics/metabolism
Male

@article {pmid42586246,
year = {2026},
author = {Manjunatha, HJ and Mahalingappa, G and Varadaraju, SR and Manjunath, SH and Prashantha, K and Damle, A and Lee, C and Kumar, A},
title = {From Food to Function: Nutraceutical-Based Modulation of Mitochondrial, Inflammatory, and Epigenetic Networks in Retinal Neurodegeneration.},
journal = {Ageing research reviews},
volume = {},
number = {},
pages = {103288},
doi = {10.1016/j.arr.2026.103288},
pmid = {42586246},
issn = {1872-9649},
abstract = {Retinal neurodegenerative diseases, such as age-related macular degeneration, diabetic retinopathy, glaucoma, and inherited retinal dystrophies, are major causes of irreversible vision loss worldwide. Although they originate from different causes, these disorders increasingly appear to share a network of cellular stress pathways, including impaired mitochondrial function, oxidative stress, endoplasmic reticulum proteostasis collapse, chronic neuroinflammation, epigenetic dysregulation, and activation of regulated cell death pathways. The interactions among these processes create an integrated stress network that gradually disrupts retinal homeostasis and promotes neuronal degeneration, which explains the failure of therapies targeting single molecular pathways. Nutraceutical compounds found in food are gaining interest as potential agents to support retinal health because many exhibit pleiotropic biological activities that influence mitochondrial function, inflammatory signaling, antioxidant defenses, and transcriptional regulation. Herein, we consolidate knowledge of the molecular mechanisms underlying retinal neurodegeneration and how major classes of nutraceuticals (polyphenols, carotenoids, omega-3 fatty acids, and metabolic modulators) may interact with these pathways. We also discuss key translational challenges in developing therapies, including poor bioavailability and differences between human phenotypes and model systems. Additionally, we highlight emerging concepts such as microbiome-dependent metabolism of nutraceuticals, personalized nutrition strategies, and advanced ocular drug-delivery technologies. Collectively, these findings support a systems-level framework in which selected nutraceuticals may influence multiple nodes of retinal stress biology, although clinical validation remains limited.},
}

@article {pmid42586515,
year = {2026},
author = {Feo, A and Quarta, A and Ramtohul, P and Faes, L and Corradetti, G and Cabral, D and Butterfield, SD and Forte, P and Eshkoly-Lior, T and Popovic, MM and Romano, MR and Banaee, T and Agarwal, A and Freund, KB and Sadda, SR and Sarraf, D},
title = {Is extensive macular atrophy with pseudodrusen a variant of age-related macular degeneration? New insights from the first multiethnic, multicentreU.S. cohort.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2026.07.008},
pmid = {42586515},
issn = {1715-3360},
abstract = {OBJECTIVE: To characterize the long-term clinical and multimodal imaging (MMI) features of extensive macular atrophy with pseudodrusen (EMAP) in a U.S.

DESIGN: Multicentre retrospective case series.

PARTICIPANTS: Patients diagnosed with EMAP between 2015 and 2025.

METHODS: Clinical records and MMI-including colour fundus photography, fundus autofluorescence, OCT, and OCT angiography-were reviewed at baseline and last follow-up.

RESULTS: Fifteen patients (30 eyes) were included, with longitudinal MMI analysis available in 11 patients (22 eyes). Median age at referral was 72 years (range, 40-76 years), and median baseline visual acuity was 0.3 logMAR (20/40). All eyes demonstrated diffuse pseudodrusen-like deposits and retinal pigment epithelium-Bruch membrane separation consistent with basal laminar deposits. Four eyes (13.3%) showed no macular atrophy at baseline, suggesting an early disease stage (stage 0). Peripheral retinal degeneration was identified in approximately 50% of eyes, and macular neovascularization developed in 25%, including 2 eyes (6.7%) with type 3 macular neovascularization. Median visual acuity declined to 0.54 logMAR (20/70) at final follow-up (P < 0.001), and 27% met criteria for U.S. legal blindness. Disease progression was observed in 59% after a median follow-up of 47.5 months (range, 4-114 months).

CONCLUSIONS: EMAP may represent a high-risk variant of age-related macular degeneration characterized by rapid progression to geographic atrophy. Critical diagnostic features include pseudodrusen-like deposits and basal laminar deposits, whereas a vertical pattern of atrophy represents the typical outcome. Atrophy may be absent in early disease stages. Genetic validation and consideration for inclusion in future atrophic AMD interventional trials are warranted.},
}

@article {pmid42586882,
year = {2026},
author = {Guang, X and Zhang, G and Wang, Y and Chai, H},
title = {Comment on "DAPL1 deficiency impairs autophagy in retinal pigment epithelium to drive age-dependent retinal pathologies".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.08.005},
pmid = {42586882},
issn = {0929-6646},
}

@article {pmid42588090,
year = {2026},
author = {Łapińska, J and Kasperczuk, K and Koba, A and Kiełczyńska, E and Forma, A and Dolar-Szczasny, J and Rejdak, R and Flieger, J and Teresiński, G and Baj, J},
title = {Bioactive Properties of Carotenoids in Ocular Diseases: Antioxidant, Anti-Inflammatory, and Neuroprotective Effects.},
journal = {Nutrients},
volume = {18},
number = {15},
pages = {},
doi = {10.3390/nu18152467},
pmid = {42588090},
issn = {2072-6643},
mesh = {Humans ; *Antioxidants/pharmacology/therapeutic use ; *Neuroprotective Agents/pharmacology/therapeutic use ; *Carotenoids/pharmacology/therapeutic use ; *Anti-Inflammatory Agents/pharmacology/therapeutic use ; *Eye Diseases/drug therapy ; Animals ; Oxidative Stress/drug effects ; Dietary Supplements ; },
abstract = {Ocular diseases are a significant public health problem worldwide and represent one of the leading causes of disability. The prevalence of visual impairment is steadily increasing, largely driven by the ageing population. Oxidative stress, chronic inflammation and neurodegenerative processes underlie the pathogenesis of many eye diseases, including age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and cataracts, contributing to progressive vision loss and functional impairment. Carotenoids such as lutein, zeaxanthin, meso-zeaxanthin, β-carotene, lycopene, and astaxanthin exhibit multidirectional biological effects, including antioxidant, anti-inflammatory, and neuroprotective properties. These compounds are selectively accumulated in the tissues of the eye, especially in the retina and macula, where they neutralise reactive oxygen species, modulate inflammatory pathways, stabilise mitochondrial function and support the survival and function of retinal ganglion cells and photoreceptors. The aim of our review was to provide a comprehensive review of current data regarding the mechanisms of action of carotenoids and their potential clinical significance in the prevention and treatment of retinal, optic nerve, lens, and eye surface diseases, including dry eye syndrome and Meibomian gland dysfunction. We identified results of available experimental and clinical research and outlined that an adequate supply of carotenoids in the diet or in the form of supplementation may support the protection of eye structures against oxidative and inflammatory damage, improve visual performance and potentially slow disease progression. However, high-quality prospective clinical trials are necessary to conclusively assess their therapeutic efficacy and establish evidence-based recommendations for clinical practice.},
}

Humans
*Antioxidants/pharmacology/therapeutic use
*Neuroprotective Agents/pharmacology/therapeutic use
*Carotenoids/pharmacology/therapeutic use
*Anti-Inflammatory Agents/pharmacology/therapeutic use
*Eye Diseases/drug therapy
Animals
Oxidative Stress/drug effects
Dietary Supplements

@article {pmid42589986,
year = {2026},
author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S},
title = {Association of Vortex Vein Morphology with Punctate Hyperfluorescence on ICGA in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {15},
number = {15},
pages = {},
doi = {10.3390/jcm15155882},
pmid = {42589986},
issn = {2077-0383},
abstract = {Background/Objectives: Punctate hyperfluorescence (PH) on indocyanine green angiography (ICGA) is frequently observed in pachychoroid disease. However, the spatial relationship between PH lesions and vortex vein abnormalities remains unclear. This study quantified PH distribution in fellow eyes of patients with unilateral neovascular age-related macular degeneration (nAMD) and examined its association with vortex vein asymmetry and watershed-zone status. Methods: This retrospective observational study included 58 fellow eyes with PH from patients with unilateral nAMD. PH lesions were quantified on late-phase ICGA images using ImageJ software. Vortex vein distribution was classified as symmetric, superior-dominant, or inferior-dominant. Eyes were also classified by the presence of a horizontal watershed zone. PH distribution was compared by vortex vein morphology. Results: A watershed zone was absent in 14 eyes (24.1%). Vortex vein distribution was asymmetric in 27 eyes (46.6%), including 17 (29.3%) superior-dominant and 10 (17.2%) inferior-dominant. Overall, 3401 PH lesions were detected. Eyes without a watershed zone had significantly more PH lesions than those with a watershed zone (p = 0.002). The proportion of superior-region PH lesions differed significantly by vertical vortex vein predominance, with preferential distribution on the dominant side (p < 0.001). Although PH distribution did not differ significantly among the four quadrants overall, 30 eyes (51.7%) had >50% of PH lesions clustered in a single quadrant. Conclusions: PH lesions were preferentially distributed on the dominant side of vortex vein asymmetry, and eyes without a watershed zone had more PH lesions. These findings indicate that PH distribution and lesion burden are associated with vortex vein morphology and watershed-zone status and may reflect underlying alterations in choroidal venous drainage.},
}

@article {pmid42590230,
year = {2026},
author = {Kashiwagi, K and Fukuba, S and Kasai, H and Fukuda, Y and Hosoda, S and Tanabe, N},
title = {Patient-Reported Visual Function and Vision-Related Quality of Life Across Ophthalmic Diseases: An Exploratory Cross-Sectional Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {15},
pages = {},
doi = {10.3390/jcm15156128},
pmid = {42590230},
issn = {2077-0383},
abstract = {Background/Objectives: Patient-reported outcomes (PROs) provide information on subjective visual function that is not fully captured by conventional clinical measures. This exploratory cross-sectional study evaluated item-level responses to an original 11-item questionnaire and their association with vision-related quality of life across ophthalmic diseases. Methods: A total of 262 participants, including patients with glaucoma, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, cataract, and individuals with long-standing severe visual impairment, completed the questionnaire and the National Eye Institute Visual Function Questionnaire-25 (VFQ-25). Associations with age, disease category, and better-eye visual acuity were examined using correlation analyses, multivariable regression, and ordinal logistic models. Results: Perceived change in vision after treatment or disease management (A6) showed the most consistent item-level associations. A6 remained associated with age after adjustment for disease category and visual acuity (β = -0.030, p < 0.001), whereas visual acuity was not associated with questionnaire domains. A6 was negatively correlated with the VFQ-25 composite score (r = -0.693, p < 0.001) and remained associated with this score in multivariable analysis (β = -0.230, p < 0.001). Conclusions: Item-level PRO responses varied across clinical backgrounds and were not adequately explained by visual acuity alone. These findings suggest that patient-perceived visual change after treatment or disease management may provide complementary information on vision-related quality of life. Further studies using validated instruments and disease-specific severity measures are needed.},
}

@article {pmid42576424,
year = {2026},
author = {Kim, BK and Min, J and Park, SH and Shin, S and Yu, S and Park, JE and Kim, S and Park, W and Ko, J and Kwon, S},
title = {Inhibition of VEGF-Induced Angiogenesis and Vascular Leakage by Bicistronic Co-Expression of Aflibercept and COMP-Ang1.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e71568},
doi = {10.1002/adhm.71568},
pmid = {42576424},
issn = {2192-2659},
support = {//National Research Foundation of Korea/ ; RS-2026-25498717//Ministry of Science and ICT/ ; RS-2023-00218543//Ministry of Science and ICT/ ; RS-2024-00512240//Korean ARPA-H/ ; //Korea Health Industry Development Institute/ ; //Ministry of Health and Welfare/ ; },
abstract = {Current anti-VEGF monotherapies for neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR) are limited by incomplete therapeutic responses, drug resistance, and the high burden of frequent intravitreal injections (IVTs). Although extensive research is underway to improve therapeutic outcomes, there remains a critical need for more effective strategies. To address this limitation, a bicistronic rAAV8 vector, Afb/cAng1, was developed to co-express aflibercept (Afb) and COMP-Ang1 (cAng1), simultaneously inhibiting VEGF signaling and activating the Tie2 pathway. In vitro characterization using conditioned medium containing secreted Afb/cAng1 showed that the treatment effectively suppresses VEGF-induced VEGFR2 phosphorylation to below basal levels while robustly activating Tie2. Consequently, the conditioned medium significantly inhibited endothelial cell migration and tube formation, and restored VE-cadherin expression compromised by VEGF stimulation or hyperglycemic conditions. Afb/cAng1 in a 3D angiogenesis-on-a-chip model reduces neovascular area and vascular permeability, showing superior efficacy compared to Afb (Eylea). In vivo choroidal neovascularization (CNV) analysis confirmed dose-dependent anti-angiogenic efficacy of rAAV8-Afb/cAng1, comparable to that of Eylea. These findings highlight Afb/cAng1 as a dual-targeting gene therapy strategy that concurrently suppresses pathological angiogenesis and promotes vascular stabilization through coordinated VEGF inhibition and Tie2 activation in AMD and DR.},
}

@article {pmid42576929,
year = {2026},
author = {Zheng, Z and Rong, G and Li, G and Zhai, Y and Liang, Y and Shi, M and Huang, J and Zhang, Y and Zhao, X and Zhuo, Q and Hong, J and Xia, W and Cheng, Y and Zhao, C},
title = {Supramolecular Nrf2-activating peptide nanotherapeutics enable deep retinal penetration and RPE targeting for dry age-related macular degeneration.},
journal = {Materials today. Bio},
volume = {40},
number = {},
pages = {103492},
pmid = {42576929},
issn = {2590-0064},
abstract = {Dry age-related macular degeneration (AMD) is a leading cause of blindness that currently lacks effective therapies. Restoring redox homeostasis in the retinal pigment epithelium (RPE) via the Keap1-Nrf2 axis offers a compelling precise therapeutic strategy. While peptide-based protein-protein interaction (PPI) inhibitors are highly specific for this axis, the delivery to the deep RPE layer remains a formidable challenge, typically restricted by electrostatic entrapment within the vitreous matrix or limited transretinal penetration. Herein, we developed a novel, mechanism-driven, supramolecular peptide nanotherapeutic (FNBP) engineered to bypass these barriers and reach the RPE layer. Driven by distinct fluorophilic self-assembly, FNBP spontaneously organizes into bio-inert nanostructures that evade vitreous adhesion and exhibit superior transretinal diffusivity and accumulation to the RPE layer. Upon RPE internalization, the assembly leverages its physicochemical properties to trigger efficient cytosolic release, allowing the payload to disrupt the Keap1-Nrf2 interaction, thereby enabling potent Nrf2 activation and restoring redox homeostasis. In a murine model of retinal degeneration, a single intravitreal injection provided sustained preservation of retinal integrity for 28 days, significantly outperforming conventional peptide formulations and clinical supplements. This work offers a precise, mechanism-based solution for RPE-targeted regulation therapies and establishes a paradigm for designing peptide nanotherapeutics that circumvent the intrinsic limitations of retinal drug delivery.},
}