@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.},
}

@article {pmid42579492,
year = {2026},
author = {Wang, S and Zhao, S and Daniels, A and Naaman, E and Gardner, A and Smith, LEH and Cepko, CL},
title = {AAV-NRF2 protects retinal and choroidal vasculature in a GDF15-dependent manner in an oxidative damage model of AMD.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {33},
pages = {e2616985123},
doi = {10.1073/pnas.2616985123},
pmid = {42579492},
issn = {1091-6490},
support = {NA//Howard Hughes Medical Institute (HHMI)/ ; },
mesh = {Animals ; *NF-E2-Related Factor 2/genetics/metabolism ; *Dependovirus/genetics ; *Oxidative Stress ; Mice ; *Choroid/blood supply/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/genetics/therapy ; Retinal Pigment Epithelium/metabolism/pathology ; Disease Models, Animal ; *Growth Differentiation Factor 15/metabolism/genetics ; *Retinal Vessels/metabolism/pathology ; },
abstract = {Oxidative stress is proposed to be a driver of age-related diseases. Age-related macular degeneration (AMD) is one such disease, where the retinal pigment epithelium (RPE) is affected early in the disease. Vasculature damage also occurs, sometimes preceding RPE damage. To model some aspects of dry AMD, we used the NaIO3 mouse model of oxidative damage. Disruption of the deep retinal vascular plexus, disorganization and death of capillaries within the choriocapillaris, and marked electroretinographic decline were observed. Adeno-associated virus (AAV) overexpressing the transcription factor, NRF2, which induces antioxidation enzymes and represses inflammation, was tested for protection of damage. The BEST1 promoter limited expression to the RPE. The RPE, photoreceptors, and vascular architecture in both retinal and choroidal compartments were protected. Conditioned medium from RPE-choroid explants, infected by AAV8/BEST1-NRF2, was sufficient to transfer partial protection in vivo, suggesting that NRF2 induces a protective secreted factor(s). Analysis of RNA-seq data nominated growth differentiation factor 15 (GDF15) as a candidate secreted mediator. Injection of recombinant GDF15 reproduced key protective phenotypes in vivo, whereas Gdf15 deficiency attenuated NRF2-mediated rescue. Pharmacologic inhibition of TGF-β receptor signaling diminished NRF2-induced protection, supporting involvement of this signaling pathway. In a laser-induced choroidal neovascularization model, intravitreal GDF15 injection reduced fluorescein leakage and lesion size. These findings support a model in which NRF2 activation in the RPE induces expression of GDF15, which is capable of protecting the RPE, photoreceptors, and the retinal and choroidal vasculature. NRF2 and GDF15 have therapeutic potential for ocular diseases, as well as for other diseases with vascular pathology.},
}

Animals
*NF-E2-Related Factor 2/genetics/metabolism
*Dependovirus/genetics
*Oxidative Stress
Mice
*Choroid/blood supply/metabolism/pathology
*Macular Degeneration/metabolism/pathology/genetics/therapy
Retinal Pigment Epithelium/metabolism/pathology
Disease Models, Animal
*Growth Differentiation Factor 15/metabolism/genetics
*Retinal Vessels/metabolism/pathology

@article {pmid42579523,
year = {2026},
author = {Kim, JH},
title = {Persistent subretinal fluid in neovascular AMD: clinical significance and implications for treatment.},
journal = {Expert opinion on biological therapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14712598.2026.2718366},
pmid = {42579523},
issn = {1744-7682},
abstract = {INTRODUCTION: In neovascular age-related macular degeneration (AMD), complete resolution of retinal fluid has traditionally been regarded as the hallmark of successful treatment, yet accumulating evidence suggests that residual subretinal fluid (SRF) may not be uniformly harmful. In this report, the cumulative evidence supporting and qualifying an 'SRF-tolerating' treatment approach is summarized.

AREAS COVERED: Relevant articles were identified through a search of the PubMed/MEDLINE database until April 2026, using terms including 'subretinal fluid,' 'intraretinal fluid,' 'neovascular AMD,' and 'anti-vascular endothelial growth factor.' The report discusses post hoc analyses of major clinical trials (CATT, VIEW, HARBOR, ARIES, and In-Eye), the randomized FLUID study, real-world cohorts, and a recent meta-analysis, covering the association of residual SRF with visual acuity and macular atrophy, contrasting evidence linking large-volume, fluctuating, or prolonged SRF with poorer outcomes, and the distinct behavior of SRF in type 3 macular neovascularization.

EXPERT OPINION: The impact of persistent SRF on outcomes has not yet been fully established, and its clinical significance is likely to depend on its volume, location, stability, duration, and the underlying lesion subtype. An SRF-tolerating approach may be considered in selected patients, but strict monitoring of fluid status and visual acuity are required to prevent undertreatment.},
}

@article {pmid42579800,
year = {2026},
author = {Shi, L and Cherukaraveedu, D and Cho, H and Ri, K and Zhou, L and Cao, Y and Kale, N and Xu, Z and Liyanage, W and Kannan, RM and Duh, EJ},
title = {Mononuclear phagocyte-specific cGAS/STING targeting suppresses experimental choroidal neovascularization.},
journal = {JCI insight},
volume = {11},
number = {15},
pages = {},
pmid = {42579800},
issn = {2379-3708},
mesh = {Animals ; *Choroidal Neovascularization/pathology/metabolism/drug therapy ; Mice ; STING Protein ; Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase ; *Membrane Proteins/metabolism/antagonists & inhibitors ; *Nucleotidyltransferases/metabolism/antagonists & inhibitors ; cGAS-STING Signaling Pathway ; Disease Models, Animal ; Mice, Inbred C57BL ; Macrophages/metabolism ; Humans ; Male ; Female ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of blindness and is characterized by pathologic angiogenesis, specifically choroidal neovascularization (CNV). Mononuclear phagocytes (MPs), including infiltrating systemic monocyte-derived macrophages and retinal microglia, play critical roles in promoting CNV. The cGAS/STING pathway is increasingly implicated in multiple neuronal and systemic diseases and recently in ocular neovascularization. Given its roles across multiple cell types and the absence of MP-targeted therapies, we investigated the MP-specific role of cGAS/STING and a strategy for its selective targeting. In the laser-induced CNV mouse model, cGAS/STING was predominantly expressed in MPs. To enable selective targeting, we used a hydroxyl dendrimer (HD) previously shown to target MPs. HD conjugated to Cy3 selectively localized to MPs in laser CNV. HD conjugated to the STING inhibitor SN-011 (HD-SN-011) effectively inhibited cGAS/STING activation in cultured MPs. In the laser-CNV model, HD-SN-011 significantly reduced CNV leakage and lesion size, both important clinical endpoints in nAMD. RiboTag profiling confirmed selective suppression of cGAS/STING signaling and inflammatory gene expression in MPs. Together, our results implicate the specific importance of MP cGAS/STING signaling in CNV and provide proof of concept for specific modulation of STING in MPs as a therapy for nAMD.},
}

Animals
*Choroidal Neovascularization/pathology/metabolism/drug therapy
Mice
STING Protein
Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
*Membrane Proteins/metabolism/antagonists & inhibitors
*Nucleotidyltransferases/metabolism/antagonists & inhibitors
cGAS-STING Signaling Pathway
Disease Models, Animal
Mice, Inbred C57BL
Macrophages/metabolism
Humans
Male
Female

@article {pmid42579803,
year = {2026},
author = {Moza, H and Jansen, E and Zackery, O and Henry, T},
title = {Isolated Ocular Relapse Following Prolonged Remission in Primary Central Nervous System Lymphoma: A Case Report.},
journal = {Journal of investigative medicine high impact case reports},
volume = {14},
number = {},
pages = {23247096261475139},
pmid = {42579803},
issn = {2324-7096},
mesh = {Humans ; Female ; Aged ; Methotrexate/administration & dosage/therapeutic use ; Rituximab/therapeutic use/administration & dosage ; *Central Nervous System Neoplasms/drug therapy/pathology ; Remission Induction ; Magnetic Resonance Imaging ; Neoplasm Recurrence, Local ; *Eye Neoplasms/drug therapy/secondary ; },
abstract = {Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma most commonly involving the brain and leptomeninges. While high-dose methotrexate (HD-MTX)-based therapy has improved outcomes, relapse remains common and typically occurs within the CNS. Isolated ocular relapse after prolonged CNS remission is uncommon and diagnostically challenging. We report the case of a 78-year-old woman diagnosed in 2020 with PCSNL presenting with subacute constitutional and neurologic symptoms found to have a right frontal periventricular mass. She achieved complete radiographic remission following induction with HD-MTX and rituximab and remained free of CNS disease for nearly five years on serial surveillance imaging. Beginning in 2023, she developed progressive unilateral visual decline that was initially attributed to age-related macular degeneration, with repeatedly negative MRI studies of the brain and orbits. In 2025, further ophthalmologic evaluation with an ocular oncologist revealed vitreous and retinal involvement confirming isolated ocular relapse in the absence of systemic recurrence. She was retreated with HD-MTX and rituximab, resulting in clinical and fundoscopic improvement. This case highlights a rare pattern of delayed isolated ocular relapse following long-term remission in PCNSL. It underscores the limitations of neuroimaging in detecting ocular disease and emphasizes the importance of continued ophthalmologic surveillance with those specifically trained in ocular oncology in patients with persistent visual symptoms. Guideline-consistent systemic retreatment may provide effective disease control even in late relapse, particularly in patients with prior methotrexate sensitivity.},
}

Humans
Female
Aged
Methotrexate/administration & dosage/therapeutic use
Rituximab/therapeutic use/administration & dosage
*Central Nervous System Neoplasms/drug therapy/pathology
Remission Induction
Magnetic Resonance Imaging
Neoplasm Recurrence, Local
*Eye Neoplasms/drug therapy/secondary

@article {pmid42570770,
year = {2026},
author = {Gu, X and Zhuang, A and Fan, J and Wen, X and Yang, L and Jia, R and Chai, P and Fan, X},
title = {Lactate signaling and lactylation in retina: From physiological Warburg effect to pathological metabolic reprogramming.},
journal = {Progress in retinal and eye research},
volume = {114},
number = {},
pages = {101509},
doi = {10.1016/j.preteyeres.2026.101509},
pmid = {42570770},
issn = {1873-1635},
abstract = {Lactate was once regarded merely as a byproduct of glycolysis, but is now recognized as a multifunctional metabolite that coordinates energy redistribution, intercellular communication, receptor-mediated signaling, and epigenetic regulation. In the retina, these functions are especially consequential because visual processing depends on a highly specialized and energetically demanding tissue, characterized by steep oxygen gradients, a dual vascular supply, and tightly integrated metabolic crosstalk among photoreceptors (PCs), Müller glia, the retinal pigment epithelium, vascular cells, and retinal ganglion cells. In this review, we synthesize current advances in lactate signaling and lactylation in the retina, and examine how their dysregulation contributes to neovascularization, inflammation, and neurodegeneration in disorders including diabetic retinopathy, age-related macular degeneration, autoimmune uveitis and glaucoma. Drawing from these metabolic insights, therapeutic interventions targeting lactate signaling and lactylation are discussed as potential approaches to mitigate retinal abnormalities. Collectively, this review highlights the central importance of lactate signaling and lactylation in retinal physiology and pathology, and provides a conceptual framework for developing metabolic interventions aimed at restoring retinal lactate homeostasis.},
}

@article {pmid42572660,
year = {2026},
author = {Duculescu, AI and Pirvulescu, R and Geamanu, A and Firinciogullari, E and Toma, E and Alexandrescu, C and Stanca, HT},
title = {Optical Coherence Tomography Angiography in Age-Related Macular Degeneration.},
journal = {Romanian journal of ophthalmology},
volume = {70},
number = {2},
pages = {191-198},
pmid = {42572660},
issn = {2501-2533},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Fluorescein Angiography/methods ; *Choroid/blood supply ; *Macular Degeneration/diagnosis/physiopathology ; Fundus Oculi ; Disease Progression ; *Retinal Vessels/diagnostic imaging/pathology ; },
abstract = {OBJECTIVE: To review and synthesize current evidence regarding the importance of optical coherence tomography angiography (OCTA) in the assessment of choriocapillaris alterations and macular neovascularization (MNV) across the spectrum of age-related macular degeneration (AMD), focusing on disease progression and clinical implications.

METHODS: Selective review of the specialized literature, concentrating on both qualitative and quantitative OCTA analyses of the retinal and choroidal microvasculature in AMD. We focused on measures related to choriocapillaris flow deficits, the morphology and maturity of MNV, and their associations with structural changes like drusen, geographic atrophy, and exudative conditions. The review included findings from both spectral-domain and swept-source OCTA systems.

RESULTS: OCTA enables non-invasive, depth-resolved visualization of choriocapillaris and MNV alterations throughout the progression of AMD. In the early and intermediate stages of AMD, localized choriocapillaris flow deficits are often observed beneath drusen and around lesion areas. In more advanced stages, there is significant choriocapillaris damage, especially near geographic atrophy and macular neovascularization. Quantitative OCTA biomarkers, such as density and flow deficit percentage, show strong correlations with disease stage, progression risk, and treatment response. Additionally, the maturity patterns of MNV identified through OCTA seem to affect the integrity of the surrounding choriocapillaris and the dynamics of atrophy.

DISCUSSION: The reviewed studies support a close relationship between choriocapillaris dysfunction, the development of macular neovascularization, and the progression of AMD. These findings reinforce the concept that vascular alterations play a central role throughout the disease spectrum and highlight the potential of OCTA to provide biomarkers that may improve prognostic assessment and treatment monitoring. However, further standardization of imaging protocols and quantitative analysis methods is needed before these biomarkers can be fully integrated into routine clinical practice.

CONCLUSIONS: OCTA has become a crucial imaging tool for understanding microvascular changes in AMD. The quantitative evaluation of the choriocapillaris and detailed analysis of MNV morphology offer important insights into disease mechanisms, progression risk, and treatment monitoring. Incorporating OCTA-derived biomarkers into routine clinical practice could improve personalized management strategies for patients across the spectrum of AMD.},
}

Humans
*Tomography, Optical Coherence/methods
*Fluorescein Angiography/methods
*Choroid/blood supply
*Macular Degeneration/diagnosis/physiopathology
Fundus Oculi
Disease Progression
*Retinal Vessels/diagnostic imaging/pathology

@article {pmid42573803,
year = {2026},
author = {Hu, L and Cao, H and Ma, X},
title = {Neovascular age-related macular degeneration trial innovation remains vascular endothelial growth factor-centred despite therapeutic diversification.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42573803},
issn = {1435-702X},
support = {81271022//National Natural Science Foundation of China/ ; },
}

@article {pmid42575302,
year = {2026},
author = {Matar, K and Delaney, A and Indurkar, A and Amine, R and Budrevich, J and Tang, A and Hu, M and Yu, HJ and Reese, J and Srivastava, SK and Wykoff, CC and Ehlers, JP},
title = {Assessment of Ellipsoid Zone Integrity and Other Quantitative OCT Biomarkers for Intermediate AMD Progression to Atrophy.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.08.005},
pmid = {42575302},
issn = {1549-4713},
abstract = {PURPOSE: To evaluate the association between baseline optical coherence tomography (OCT) biomarkers and 2-year disease progression from intermediate age-related macular degeneration (iAMD) to advanced atrophic AMD, defined by OCT, with emphasis on ellipsoid zone (EZ) attenuation/loss and other quantitative structural features.

DESIGN: Retrospective cohort study.

PARTICIPANTS: 502 eyes with iAMD and no evidence of atrophy (i.e., RPE loss with associated outer retinal atrophy) or exudation at baseline, each with 2-year follow-up OCT imaging.

METHODS: Baseline and 2-year spectral-domain OCT scans were analyzed using a validated, machine learning-enhanced multilayer segmentation platform with subsequent certified reader review and correction. Quantitative OCT parameters included EZ-RPE thickness, partial and total EZ attenuation, drusen volume, hyperreflective foci (HRF) count, total RPE loss, and outer nuclear layer-RPE (ONL-RPE) thickness. Fully automated deep-learning models quantified hypertransmission and EZ at-risk (i.e., a model developed to identify areas of abnormal EZ-RPE thinning in the absence of RPE loss). A random forest classifier was trained using baseline features, with performance assessed using 5-fold stratified cross-validation.

MAIN OUTCOME MEASURES: Development of OCT-defined advanced atrophic AMD defined by total RPE loss with associated outer retinal atrophy with an area ≥0.05 mm[2] (i.e., cRORA equivalent) at 2 years and baseline OCT biomarkers associated with progression.

RESULTS: Eyes that developed advanced atrophic AMD showed significantly greater partial and total EZ attenuation, reduced EZ-RPE and ONL-RPE thickness, higher drusen volume, and greater HRF counts than non-converters (all p<0.05). Deep-learning-derived EZ at-risk and hypertransmission metrics were also significantly higher in converters. The cross-validated predictive model incorporating all baseline features achieved a mean area-under-the-ROC curve (AUC) of 0.85 ± 0.02. EZ integrity metrics and HRF count ranked as the most influential predictors of progression.

CONCLUSIONS: Quantitative OCT biomarkers, particularly EZ integrity measures and HRF count, are strongly associated with 2-year progression to advanced atrophic AMD in iAMD. These findings support the role of quantitative EZ integrity metrics and hyperreflective foci features for early disease risk stratification and may inform the design of prevention-focused or early-intervention clinical trials aimed at delaying the onset of atrophic changes.},
}

@article {pmid42575959,
year = {2026},
author = {Sun, G and Zeraatkar, D and Man, REK and Ghadimi, M and Pedro Lima, J and Sivaprasad, S and Borrelli, E and Steel, DH and Guymer, RH and Wong, TY and Wykoff, CC and Ma, J and Chaudhary, V},
title = {Correction: Vision-related quality of life in non-neovascular age-related macular degeneration: a protocol for systematic review and meta-analysis.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41433-026-04787-5},
pmid = {42575959},
issn = {1476-5454},
}

@article {pmid42576020,
year = {2026},
author = {Lee, WA and Tsai, DH and Lai, EC},
title = {Real-world safety of aflibercept 8 mg in neovascular age-related macular degeneration.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42576020},
issn = {1432-1912},
abstract = {Aflibercept 8 mg is a higher-dose intravitreal anti-vascular endothelial growth factor formulation developed to extend treatment intervals in neovascular age-related macular degeneration (nAMD). Although pivotal trial data have supported its ocular safety profile, real-world evidence regarding intraocular inflammation (IOI) after aflibercept 8 mg remains limited. This study evaluated the real-world patient-level risk of newly coded IOI following aflibercept 8 mg initiation among patients with nAMD in a large multi-institutional electronic health record network. We conducted a retrospective cohort study using the TriNetX U.S. Collaborative Network. Patients with nAMD who received aflibercept 8 mg were identified using RxNorm code 1,232,150 with a strength restriction of 114.3 mg/mL and were required to have a prior or concurrent diagnosis of unspecified macular degeneration, exudative age-related macular degeneration, or retinal neovascularization. The index date was defined as the first recorded administration of aflibercept 8 mg. Newly coded IOI was assessed from 1 to 365 days after the index date and defined as acute or subacute iridocyclitis, retinal vasculitis, unspecified iridocyclitis, or posterior cyclitis. Patients with any component IOI diagnosis before the outcome window were excluded from the risk analysis. The mean age was 77.7 ± 10.1 years; 59.6% of patients were female, and 83.4% were White. After excluding patients with pre-existing IOI, 1,670 patients were eligible for outcome analysis. During the 365-day follow-up, 29 patients had newly coded IOI, corresponding to an observed patient-level risk of 1.74% (95% CI, 1.17%-2.48%). The mean follow-up was 281.5 ± 124.6 days, with a median of 365 days and an interquartile range of 162 days. Kaplan-Meier analysis showed an IOI-free survival probability of 97.89% at 365 days, corresponding to a Kaplan-Meier-estimated cumulative incidence of 2.11% (95% CI, 1.47%-3.04%). The low frequency of newly coded IOI provides preliminary descriptive reassurance. However, the absence of an active comparator, potential outcome misclassification, and the limited event count preclude definitive conclusions regarding comparative ocular safety.},
}

@article {pmid42567877,
year = {2026},
author = {Sivaprasad, S and Stewart, MW and Wykoff, CC and Eichenbaum, D and Korobelnik, JF and Lanzetta, P and Chaudhary, V and Cheung, CMG and Gale, R and Munk, MR and Sakamoto, T and Stahl, A and Zarranz-Ventura, J and Wong, TY and Holz, FG and Loewenstein, A},
title = {Aflibercept 8 mg in neovascular age-related macular degeneration and diabetic macular oedema: Translating clinical trials into clinical practice.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42567877},
issn = {1476-5454},
abstract = {Provide expert-informed guidance on the integration of aflibercept 8 mg into routine clinical care for patients with neovascular age-related macular degeneration (nAMD) and diabetic macular oedema (DMO), based on clinical trial and real-world evidence. Sixteen retina specialists ('experts') met during the Association for Research in Vision and Ophthalmology (ARVO) annual meeting in May 2025 to discuss the clinical use of aflibercept 8 mg. A post-meeting online platform was used to collect additional independent input. Agreement was captured using binary responses and categorised as: all agreed (100%), majority agreed (≥ 75%), most agreed (50-74%), or non-consensus (≤ 50%). All experts agreed that aflibercept 8 mg may be considered as a first-line treatment in treatment-naïve patients with nAMD and DMO, and switching to aflibercept 8 mg can be considered for previously treated patients. The majority of experts agreed that switching patients with well-controlled disease on shorter or intermediate dosing intervals may enable further interval extension while maintaining disease control, and switching patients with poorly controlled disease may optimise anatomical outcomes and improve stability. Most experts agreed that three initial monthly loading doses are appropriate in newly diagnosed patients. No consensus was reached on optimal dosing-decision strategies after switching in patients with poorly controlled disease, nor on the timing of initial interval modification during treatment initiation. These expert opinions, informed by available, emerging clinical evidence and real-world clinical experience, support aflibercept 8 mg as a first-line and switch option for nAMD and DMO, using personalised treatment approaches for both treatment-naïve and previously treated patients.},
}

@article {pmid42568574,
year = {2026},
author = {Lewis-Luján, LM and Iloki Lewis, AP and Guerrero Magaña, DE and Alvarez Chavez, CR and Osadchuk, MA and Trushin, MV and Galvez Ruiz, JC and Vargas Durazo, JT and Perez Martinez, CJ and Trujillo López, S and Iloki-Assanga, SB},
title = {Marine nutraceuticals from Mexican Pacific Sargassum targeting oxidative stress and inflammation in age-related macular degeneration.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1888072},
pmid = {42568574},
issn = {2296-861X},
abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal neurodegenerative disease characterized by oxidative stress, chronic inflammation, retinal pigment epithelium (RPE) dysfunction, and progressive central vision loss. Marine-derived bioactive compounds from Mexican Pacific Sargassum species have emerged as promising nutraceutical candidates due to their antioxidant, anti-inflammatory, and cytoprotective properties. This narrative review critically examines the nutritional composition and pharmacologically relevant bioactive constituents of Mexican Pacific Sargassum, with emphasis on fucoxanthin, fucoidans, phlorotannins, and polyunsaturated fatty acids. Particular attention is given to their molecular mechanisms of action in AMD-related pathways, including modulation of oxidative stress, Nrf2/HO-1 signaling, NF-κB-mediated inflammation, VEGF-associated angiogenesis, mitochondrial dysfunction, and apoptosis in retinal cells. Current evidence from preclinical retinal models suggests that these compounds may exert protective effects against AMD progression through multipronged regulation of redox and inflammatory pathways. Additionally, major translational challenges related to bioavailability, extraction standardization, safety, and the absence of AMD-specific clinical trials are critically discussed. Overall, Mexican Pacific Sargassum represents a promising yet underexplored source of marine bioactives with potential applications in the development of nutraceutical strategies targeting retinal degeneration and AMD.},
}

@article {pmid42569289,
year = {2026},
author = {Ehrenzeller, C and MacLaren, RE},
title = {Interactions Between Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101287},
pmid = {42569289},
issn = {2666-9145},
abstract = {CLINICAL RELEVANCE: Age-related macular degeneration (AMD) remains the leading cause of irreversible blindness in Western populations, with no approved therapies for the dry form characterized by drusen accumulation and retinal pigment epithelium atrophy. This review examines extracellular matrix alterations in Bruch's membrane by comparing healthy aging, AMD pathogenesis, and Doyne Honeycomb Retinal Dystrophy-a monogenic disorder that serves as a surrogate model for AMD due to similar phenotypic manifestations.

METHODS: We focus on the critical interactions between epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1), matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases-3, and complement factors. We explore their roles in extracellular matrix homeostasis disruption. In healthy aging, oxidative stress and inefficient waste removal drive gradual matrix remodeling and low-grade inflammation. Age-related macular degeneration results from polygenic risk variants in complement and extracellular matrix genes, combined with environmental stressors, leading to accelerated matrix dysfunction and chronic complement activation. In Doyne Honeycomb Retinal Dystrophy, the EFEMP1 R345W mutation causes rapid disease progression through impaired protein secretion, abnormal matrix accumulation, and complement dysregulation.

RESULTS: Our analysis reveals that EFEMP1-tissue inhibitor of metalloproteinases-3 complexation may represent a critical threshold in drusen formation across both conditions, AMD and Doyne Honeycomb Retinal Dystrophy.

CONCLUSION: While AMD pathogenesis unfolds over decades through cumulative insults, the EFEMP1 mutation compresses similar pathological changes into 30 to 40 years, suggesting this mutation acts as a major hazard for matrix homeostasis disruption. Understanding these shared mechanisms provides insights into therapeutic targets, including complement inhibition, MMP modulation, and EFEMP1-directed interventions. We propose continued investigation of Doyne Honeycomb Retinal Dystrophy as a valuable model for identifying AMD treatments.

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

@article {pmid42569388,
year = {2026},
author = {Bodmer, NS and Guezelguen, M and Huber, L and Howell, J and Faes, L and Bachmann, LM and Fu, DJ and Spooner, K and Sivaprasad, S and Schmid, MK},
title = {Vision-Related Patient-Reported Outcomes in Randomized Controlled Trials of Age-Related Macular Degeneration: A Systematic Review.},
journal = {Ophthalmology science},
volume = {6},
number = {9},
pages = {101308},
pmid = {42569388},
issn = {2666-9145},
abstract = {TOPIC: This systematic review examined how vision-related patient-reported outcome measures (PROMs) were selected, operationalized, and reported at baseline in randomized controlled trials (RCTs) enrolling patients across the spectrum of age-related macular degeneration (AMD).

CLINICAL RELEVANCE: Age-related macular degeneration is a major cause of visual disability, and visual acuity alone does not fully capture its effects on everyday functioning and quality of life. Inconsistent selection and incomplete reporting of PROMs may limit interpretation, comparison across trials, and evidence synthesis.

METHODS: A systematic search of Medical Literature Analysis and Retrieval System Online, Embase, Web of Science Core Collection, and Scopus was conducted from database inception to September 27, 2023, supplemented by a targeted update for relevant 2024 and 2025 publications. Eligible studies were RCTs enrolling ≥20 participants with AMD and reporting both baseline visual acuity and baseline vision-related PROM data. Data on PROM instrument selection, scoring, baseline distributions, laterality context, and subgroup reporting were extracted and synthesized descriptively.

RESULTS: Thirty-eight RCTs met the inclusion criteria, spanning early through late-stage AMD. Across included trials, 11 distinct PROM instruments were reported. The National Eye Institute Visual Function Questionnaire family predominated (78.9%), with the National Eye Institute Visual Function Questionnaire‑25 being the most commonly used version (n = 17). Baseline patient-reported functional status varied by disease stage: early and intermediate AMD cohorts reported higher scores (75.3-89.1), whereas trials enrolling neovascular AMD patients showed lower and more heterogeneous scores (59.1-77.9). Subscale and domain reporting was inconsistent, with many trials presenting only composite scores or a limited subset of subscales. Baseline PROM results were not reported by subgroup, preventing comparisons across patient populations. Reporting of visual function was incomplete with only 13% of studies reporting both better-seeing and worse-seeing eyes.

CONCLUSION: The interpretive value of PROMs in AMD trials is constrained by inconsistent baseline reporting and limited reporting of both-eye and binocular acuity needed to contextualize patient-level function. Enhanced consistency in stage-appropriate PROM selection and routine reporting of baseline distributions are essential to support patient-centered evaluation and evidence synthesis in AMD research.

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

@article {pmid42570084,
year = {2026},
author = {Ahuja, AS and Vasu, P and Wagner, IV and Hwang, TS and Dorairaj, SK and Young, BK},
title = {Racial and ethnic disparities in faricimab injections: a propensity matched cohort study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42570084},
issn = {1435-702X},
abstract = {PURPOSE: To evaluate potential racial and ethnic disparities in the utilization of faricimab-svoa in the management of macular edema (ME) and neovascular age-related macular degeneration (nAMD).

METHODS: A retrospective cohort study using the TriNetX database analyzed patients diagnosed with nAMD, type 2 diabetes with diabetic macular edema (DME), or retinal vein occlusion macular edema (RVO ME), grouped by Hispanic ethnicity, African American (AA) race, and non-Hispanic, non-AA controls. Propensity score matching was conducted for age, gender, diabetes mellitus, essential hypertension, obesity, ischemic heart disease, and atherosclerotic heart disease. The primary outcome was faricimab-svoa injection incidence at any time point after diagnosis. Odds ratios (ORs) were calculated between cohorts.

RESULTS: Of 49,568 AA patients (mean [SD] age at injection, 68.3 [14.4] years; 58.5% women) with a diagnosis of nAMD or ME, 55 received faricimab injection (OR 0.162; 95% CI, 0.122-0.215) compared to 338 in the control group of the same size. A similar relationship was noted for Hispanic patients (mean [SD] age at injection, 66.6 [13.5] years; 50.1% women) who received the injection (25 of 13,520) compared to non-Hispanic patients (91 of 13,520) (OR 0.273; 95% CI, 0.176-0.426).

CONCLUSION: Faricimab is underutilized in the management of ME and nAMD in patients with AA race and Hispanic ethnicity compared to propensity score matched controls.},
}

@article {pmid42567397,
year = {2026},
author = {Wang, Y and Luo, T and Li, C and Zhou, L and Lin, H and Yang, MM},
title = {Cellular senescence in posterior segment neovascular diseases: A proposed feed-forward amplification model.},
journal = {Experimental eye research},
volume = {272},
number = {},
pages = {111189},
doi = {10.1016/j.exer.2026.111189},
pmid = {42567397},
issn = {1096-0007},
abstract = {Neovascular age-related macular degeneration (nAMD) and proliferative diabetic retinopathy (PDR) continue to be significant contributors to permanent visual impairment. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has substantially improved disease management, recurrent neovascularization, persistent leakage, incomplete treatment response, subretinal fibrosis in nAMD, and fibrovascular membrane formation or tractional complications in PDR indicate that disease progression involves mechanisms beyond VEGF signaling alone. Cellular senescence-a stress-induced condition marked by persistent cell-cycle arrest, altered stress responses, and context-dependent senescence-associated secretory phenotype (SASP) activity-has been identified as a potential pathogenic amplifier in posterior-segment neovascular diseases. Chronic oxidative stress, hyperglycemia, hypoxia, metabolic dysfunction, and inflammation in the retina and choroid may induce senescence-associated or senescence-like remodeling in retinal pigment epithelial cells, Müller glia, endothelial cells, and pericytes. Nonetheless, conclusive evidence of bona fide cellular senescence in human ocular tissues remains scarce and varies markedly across cell types and disease contexts. This review integrates direct experimental evidence, marker-based observations, and inferred mechanistic insights to delineate a proposed, evidence-based senescence-associated feed-forward amplification model. In this model, chronic pathological stress may initiate or reinforce senescence-related programs, whereas SASP factors, extracellular vesicles, and immune microenvironment remodeling may further amplify angiogenic, inflammatory, vascular, and fibrotic dysfunction. Importantly, this model should be interpreted as a hypothesis-generating, non-exclusive framework rather than a fully established causal pathway. We also compare disease-specific features of nAMD and PDR, discuss methodological challenges in defining retinal senescence, and evaluate the translational potential and safety concerns of senolytics and SASP-modulating strategies as adjuncts to anti-VEGF therapy. Rather than presenting cellular senescence as a fully established causal driver, this review frames senescence-associated remodeling as a context-dependent, evidence-stratified amplifying component within this proposed feed-forward framework.},
}

@article {pmid42561799,
year = {2026},
author = {Xu, Y and Xu, M and Qie, J and Yu, B and He, X and Zhou, Y and Zhang, L and Jin, Q and Ye, J and Han, H},
title = {A boronate-phenolic network nanoplatform carrying dimethyl itaconate for ameliorating neovascular age-related macular degeneration.},
journal = {Biomaterials},
volume = {337},
number = {},
pages = {124528},
doi = {10.1016/j.biomaterials.2026.124528},
pmid = {42561799},
issn = {1878-5905},
abstract = {Age-related macular degeneration (AMD), particularly its neovascular form driven by choroidal neovascularization (CNV), remains leading cause of irreversible blindness worldwide. Current anti-vascular endothelial growth factor (VEGF) therapy offers limited efficacy, indicating that monotherapies targeting the downstream VEGF pathway cannot meet clinical needs, thus highlighting the demand for upstream and multifunctional therapeutic strategies. In this study, a boronate-phenolic network was constructed by cross-linking antioxidant tannic acid (TA) with ((1,3,5-Triazine-2,4,6-triyl)tris(benzene-4,1-diyl))triboronic acid (TBPT), in the presence of polyethylene glycol (PEG) for stabilization. Anti-inflammatory dimethyl itaconate (DMI) was further encapsulated, resulting in DTTP nanoparticles. With this multifunctional design, DTTP effectively promoted ROS elimination and mitochondrial protection, reestablished glutathione homeostasis, and downregulated genes involved in pyroptotic and inflammatory pathways. In a laser-induced CNV mouse model, intravitreal DTTP exhibited robust therapeutic efficacy with a favorable safety profile, achieving a 71.8% reduction in neovascularization and a 57.4% reduction in vascular leakage, with aflibercept serving as a clinically relevant benchmark. Collectively, DTTP represents a promising multifunctional nanotherapeutic for the management of neovascular AMD (nAMD).},
}

@article {pmid42562233,
year = {2026},
author = {Narayan, A and Issa, PC and Yusuf, IH and MacLaren, RE},
title = {CDHR1-associated retinal degeneration: Clinical phenotypes and therapeutic approaches.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101508},
doi = {10.1016/j.preteyeres.2026.101508},
pmid = {42562233},
issn = {1873-1635},
abstract = {CDHR1 is a recently identified cause of autosomal recessive retinal degeneration manifesting as three distinct clinical phenotypes: macular dystrophy, cone-rod dystrophy or retinitis pigmentosa. In this review, we summarise the discovery and characterisation of CDHR1, clinical phenotypes, natural history and therapeutic approaches including gene supplementation and CRISPR gene editing. CDHR1 is a non-classical cadherin that is highly expressed in cone and rod photoreceptors and is essential for the higher-order organisation of the functionally critical outer segments. Promising pre-clinical data show that AAV gene supplementation therapy delivered by subretinal injection can lead to long-term morphological, structural, functional and behavioural improvements in the Cdhr1 knockout mouse model. Notably, CDHR1 supplementation restored full-length photoreceptor outer segments that are usually shortened and disorganised in disease models and prolonged photoreceptor survival - key mechanisms for the functional and behavioural rescue effects that were observed. The disease is likely to be underdiagnosed because CDHR1-associated macular dystrophy - likely to be the most common disease phenotype - is most often caused by a 'silent' nucleotide substitution that has previously been overlooked by genetic testing. Since the macular dystrophy phenotype has phenotypic similarities to advanced dry age-related macular degeneration (AMD), misdiagnoses are common. CDHR1-associated macular dystrophy also shares phenotypic features with a variety of monogenic masquerades such as ABCA4, PRPH2 and GUCY2D-associated macular dystrophies; we present a flowchart to guide the clinical distinction of these disorders which is now critical for patients as their treatments diverge. AAV gene therapy may be beneficial across the CDHR1 disease spectrum - including those with hypomorphic variants associated with macular dystrophy or retinitis pigmentosa. The coding sequence fits into AAV and with the macular dystrophy phenotype, there is a large time window for potential intervention and a large treatable population. Hence clinical trials are anticipated. It is therefore important that patients with CDHR1-associated retinal degeneration are accurately phenotyped and genetically confirmed to support the application of CDHR1 gene therapy.},
}

@article {pmid42562278,
year = {2026},
author = {Zhuang, X and Olivieri, C and Neri, G and Ricardi, F and Monici, G and Viggiano, P and Boscia, F and Pauleikhoff, D and Sadda, S and Sarraf, D and Staurenghi, G and Reibaldi, M and Borrelli, E},
title = {Macular atrophy in neovascular age-related macular degeneration: Prevalence, risk factors, imaging features, and clinical implications.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.08.002},
pmid = {42562278},
issn = {1879-3304},
abstract = {Macular atrophy (MA) is a major cause of long-term visual decline in neovascular age-related macular degeneration (nAMD), despite the ability of anti-vascular endothelial growth factor (anti-VEGF) therapy to control exudation. We summarize current evidence on the definition, epidemiology, risk factors, imaging features, and functional consequences of MA in nAMD. Optical coherence tomography (OCT) has improved the identification of atrophic changes and supports distinguishing complete retinal pigment epithelium and outer retinal atrophy from fibro-atrophy, a proposed OCT-based category in which outer retinal and RPE loss occur beneath hyperreflective or fibrotic tissue that makes choroidal hypertransmission absent or unassessable. In treated eyes, long-term studies show that MA becomes increasingly common over time and is a major factor limiting durable visual benefit, yet epidemiologic estimates remain difficult to compare because MA definitions, imaging modalities, lesion-size thresholds, and terminology varies substantially across studies. Important risk factors include older age, poor baseline visual acuity, type 3 macular neovascularization, intraretinal fluid, subretinal hyperreflective material, and early atrophic signs on baseline imaging, whereas type 1 neovascularization may be associated with slower atrophy progression. Once established, MA substantially affects visual function, not only reducing visual acuity, but also impairing reading speed and other visual functions. A major unresolved controversy is whether cumulative anti-VEGF exposure contributes independently to MA, rather than reflecting more severe or recurrent exudative disease. Future progress will depend on standardized definitions, multimodal imaging, and predictive models to guide personalized management and develop therapies targeting atrophy.},
}

@article {pmid42566331,
year = {2026},
author = {Simond, B and Fenniri, I and Chirpaz, N and Elbany, S and Rocher, A and Gilli, C and Chacun, S and Voirin, N and Burillon, C and Matagrin, B and Dot, C},
title = {Evaluation of treatment interval extension and short-term stability after switching to faricimab in neovascular AMD, a mid-term observational study.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1},
doi = {10.1159/oph/aeeag007},
pmid = {42566331},
issn = {1423-0267},
abstract = {INTRODUCTION: The SHIFT-HB study (SwitcH Faricimab Treatment in High Burden patients) aimed to evaluate the anatomical and functional outcomes -and the short-term stability of extended dosing intervals- after switching to faricimab in high treatment burden (HB) neovascular age-related macular degeneration (nAMD) previously treated with first-generation anti-VEGF agents. The primary aim was to assess treatment interval changes after 6 intravitreal injections (IVI) and the persistence of interval gains between the 5th and 6th faricimab IVI.

METHODS: Single-center, retrospective real-world study (November 2023-November 2024; tertiary center Edouard Herriot Hospital, Lyon). Eligible eyes had nAMD requiring ≤8-weeks intervals despite ≥6 prior aflibercept or ranibizumab injections. After the switch, all eyes received ≥6 faricimab IVIs under a proactive Treat-and-Extend regimen. Short-term stability was defined, among eyes with any interval gain, as a prescribed interval at V6 identical to or longer than that at realized at V5.

RESULTS: 190 eyes from 158 patients (mean age 81 ± 7.5 years; 57.9% female) were included. The mean pre-switch interval was 4.9 ± 1.2 weeks and increased to 6.7 weeks after 6 faricimab IVIs (p=5.85x10-20). Interval increased in 61.6% of eyes; among these, 45% gained ≥ 3 weeks (range +3 to +8). Short-term stability between V5 and V6 occurred in 82.3% of responders. The maximum interval was first achieved at V6 in 52.1% of responder eyes. Among eyes with paired baseline and V6 measurements, best corrected visual acuity remained stable (69.2 vs 71.2 ETDRS letters; p=0.67), while central retinal thickness (CRT) decreased (303.1 µm to 287.2 µm; p=9.98x10-4). Intraocular inflammation occurred in 7 eyes (3.7%; 0.61% of injections) and led to drug discontinuation.

CONCLUSION: In real world HB nAMD, switching to faricimab enabled a significant extension of injection intervals in nearly two-thirds of eyes while maintaining vision and improving OCT anatomy, supporting faricimab as a strategy to reduce treatment burden in this difficult to treat population.},
}

@article {pmid42566756,
year = {2026},
author = {Sassi, H and Miere, A and Oubraham, H and Kaoudio, D and Ionita, D and El Filali, M and Bourroubey, A and Wang, X and Jung, C and Souied, E},
title = {OUTCOMES AND HEALING PROCESS OF RETINAL PIGMENT EPITHELIAL TEARS IN AMD PATIENTS: A 5-YEAR RETROSPECTIVE OBSERVATIONAL CASE SERIES.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004960},
pmid = {42566756},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the incidence of retinal pigment epithelium (RPE) remodeling after RPE tears in age-related macular degeneration (AMD) and assess its association with visual outcomes over a 5-year follow-up.

METHODS: This retrospective observational study reviewed AMD eyes with RPE tears and a minimum follow-up of 5 years. Changes in best-corrected visual acuity (BCVA) were recorded, and the presence and delay to development of tear-associated retinal pigment epithelial proliferation (TARP) were evaluated.

RESULTS: Twenty-six eyes from 23 patients were included. Mean age was 80.08 ± 6.67 years. Baseline BCVA was 0.83 ± 0.52 logMAR (Snellen equivalent 20/125), and final BCVA declined to 1.05 ± 0.54 logMAR (20/200) (p = 0.028). Mean follow-up was 6.25 ± 1.25 years. Both the greatest linear diameter and the area of RPE loss increased significantly from baseline to year 5 (p = 0.012 and p = 0.009, respectively). TARP was observed in 54.2% of eyes at 5 years, with a mean onset of 293 ± 258 days. Final BCVA was significantly worse in eyes with subretinal hemorrhage (p = 0.02), while the presence of TARP was not associated with visual outcome (p = 0.21). At 5 years, BCVA declined in both groups (with and without TARP), with no significant difference (p = 0.21).

CONCLUSIONS: Approximately half of the eyes with RPE tears developed TARP, typically within the first year. TARP did not confer a visual benefit. These findings suggest that anatomical remodeling of RPE tears may occur without translating into improved visual outcomes.},
}

@article {pmid42558742,
year = {2026},
author = {Mou, H and Zhang, CJ},
title = {Association between frailty and incidence of AMD among middle-aged and older people: evidence from the UK Biobank.},
journal = {Frontiers in aging},
volume = {7},
number = {},
pages = {1838979},
pmid = {42558742},
issn = {2673-6217},
abstract = {BACKGROUND: To explore the association between age-related macular degeneration (AMD) and frailty and the link between frailty and neurological aging diseases in AMD patients.

METHODS: This study included 354,334 individuals aged ≥40 years without AMD at baseline from the UK Biobank. Frailty was assessed using the Fried phenotype. Cox proportional hazard models were used to analyze the association between frailty and AMD incidence. Logistic regression models were used to examine the link between frailty and nervous system-related diseases among AMD patients.

RESULTS: Frailty was associated with AMD incidence (hazard ratio [HR] 1.36 [95% confidence interval [95% CI] 1.29-1.44] for prefrailty; HR 2.12 [95% CI 1.86-2.42] for frailty). All five frailty components were associated with AMD: weight loss (HR 1.11 [95% CI 1.03-1.20]), exhaustion (HR 1.13 [95% CI 1.03-1.23]), low physical activity (HR 1.12 [95% CI 1.01-1.23]), low grip strength (HR 1.23 [95% CI 1.14-1.32]), and slow walking pace (HR 1.23 [95% CI 1.12-1.35]). Additionally, among AMD patients, frailty was linked to neurodegenerative diseases (odds ratio [OR] 3.09 [95% CI 1.58-6.07]), neurovascular diseases (OR 3.77 [95% CI 2.16-6.60]), and mental diseases (OR 2.09 [95% CI 1.12-3.93]).

CONCLUSION: Frailty is a significant risk factor for AMD incidence, with all five components showing a positive association with AMD. Furthermore, frailty is linked to neural system-related diseases in AMD patients. Early detection and intervention for frailty may help prevent or delay AMD onset.},
}

@article {pmid42560008,
year = {2026},
author = {Larsen, PP and Linard, M and Schweitzer, C and Delyfer, MN and Korobelnik, JF and Helmer, C and Delcourt, C},
title = {Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {14},
doi = {10.1167/iovs.67.10.14},
pmid = {42560008},
issn = {1552-5783},
mesh = {Humans ; *Macular Degeneration/etiology ; *Diabetic Retinopathy/etiology ; *Endotoxemia/complications ; Animals ; *Glaucoma/etiology ; Lipopolysaccharides ; Oxidative Stress ; },
abstract = {Lipopolysaccharide (LPS), a component of Gram-negative bacteria, is a potent activator of the innate immune system and has been implicated in the pathogenesis of eye diseases, including age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), and diabetic retinopathy (DR). LPS enters systemic circulation through bacterial lysis or active secretion, leading to endotoxemia-either acute or chronic. Chronic endotoxemia, often resulting from gut dysbiosis, may link microbial imbalances to eye diseases. Indeed, chronic LPS exposure may contribute to both systemic and local inflammation. Within the retina, it activates resident immune and structural cells triggering pro-inflammatory cytokine production, oxidative stress, complement cascade activation, and inflammasome activation. These immune cascades compromise blood-retinal barrier integrity, increase vascular leakage, and impair neuronal viability. LPS exposure can stimulate the secretion of pro-angiogenic factors, promoting the development of neovascularization within the retina. Furthermore, the aging retina may be particularly vulnerable to LPS-mediated damage due to an increased exposure to LPS (linked to microbial dysbiosis and alterations of both intestinal and blood-retinal barriers) as well as a reduced capacity for repair. Although direct human evidence remains limited, emerging experimental data support a mechanistic role for LPS in AMD, glaucoma, and DR. This review emphasizes that addressing the impact of chronic endotoxemia represents a promising avenue for both understanding and treating eye diseases. Continued investigation into the multifaceted roles of LPS may yield innovative biomarkers and therapeutic targets to slow or prevent neurodegenerative, vascular, and inflammatory processes underlying conditions such as AMD, glaucoma, and DR.},
}

Humans
*Macular Degeneration/etiology
*Diabetic Retinopathy/etiology
*Endotoxemia/complications
Animals
*Glaucoma/etiology
Lipopolysaccharides
Oxidative Stress

@article {pmid42560501,
year = {2026},
author = {Özkaya, D and Nazıroğlu, M},
title = {Psalmotoxin-1, a novel TRPM2 channel antagonist, reduces age-related macular degeneration-caused mitochondrial oxidative damage and apoptosis in human retinal pigment epithelial (ARPE-19) cells.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42560501},
issn = {1435-702X},
support = {2024-05//BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry LTD, Isparta, Türkiye/ ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) develops as a result of mitochondrial reactive oxygen species (mitROS) and apoptosis caused by increased Ca[2+] influx via the overstimulation of transient receptor potential melastatin 2 (TRPM2). Psalmotoxin-1 (PSTX) has acid-sensing ion channel (ASIC) inhibitor and antioxidant actions in several cells. PSTX has been shown to modulate hypoxia-induced oxidative cytotoxicity and cell death in mouse eye cells by inhibiting ASIC-mediated Ca[2+] influx; however, this mechanism does not apply to AMD. In this study, we investigated how PSTX inhibits TRPM2 to protect human retinal pigment epithelium - 19 (ARPE-19) cells against mitROS damage and apoptosis caused by sodium iodate (SoI).

MATERIALS AND METHODS: Control (CONT), 20 nM PSTX for 24 h, 10 mM SoI for 24 h, SoI + PSTX, and SoI + TRPM2 antagonist (25 µM N-(p-amylcinnamoyl) anthranilic acid, ACA) groups were induced in the ARPE-19 cells.

RESULTS: The ADP-ribose-induced TRPM2 current density, Fe[2+], and H2O2-induced cytosolic Ca[2+] concentrations were elevated by the SoI treatment. Additionally, its treatment increased the markers of apoptosis, caspases (caspase-3, -8, and - 9), oxidative stress, and mitochondrial membrane dysfunction while lowering glutathione (GSH), glutathione peroxidase (GSH-Px), and cell viability number. GSH, GSH-Px, and cell viability were enhanced, whereas oxidative stress and cell death indicators were decreased via TRPM2 inhibition by the treatments of PSTX and ACA.

CONCLUSION: The results of the preliminary study indicated that PSTX incubation blocked TRPM2-mediated Ca[2+] signaling, reducing AMD-induced mitochondrial oxidant injury and cell death. PSTX, a new TRPM2 antagonist, may be utilized to treat oxidative stress and aberrant Ca[2+] influx induced by AMD.},
}

@article {pmid42560951,
year = {2026},
author = {, },
title = {Expression of Concern: Serum lipids mediate the association of per- and polyfluoroalkyl substances exposure and age-related macular degeneration.},
journal = {PloS one},
volume = {21},
number = {8},
pages = {e0355440},
pmid = {42560951},
issn = {1932-6203},
}

@article {pmid42549264,
year = {2026},
author = {Yılmaz, AC and Mutlu, FM},
title = {Prevalence of Occult Macular Pathologies Detected by Optical Coherence Tomography in Patients Scheduled for Cataract Surgery.},
journal = {Beyoglu eye journal},
volume = {11},
number = {2},
pages = {95-102},
pmid = {42549264},
issn = {2587-0394},
abstract = {OBJECTIVES: To investigate the prevalence of macular pathologies detectable only by optical coherence tomography (OCT) and not suspected on fundoscopic examination before cataract surgery in a large series of Turkish patients and to determine associated risk factors.

METHODS: Medical records of patients who underwent cataract surgery, had normal fundoscopic findings during preoperative evaluation, and underwent macular OCT were retrospectively reviewed for demographic data, ophthalmological findings, and systemic examination results. Patients were divided into normal and abnormal OCT groups according to their macular OCT results. Patients in the abnormal OCT group were further analyzed for the prevalence of OCT-detected occult macular pathologies and associated risk factors.

RESULTS: Data from 1.091 eyes were included in the study. Macular pathology was detected on OCT in 9.2% of patients. Among these patients, 40 (40%) had age-related macular degeneration, 31 (31%) had epiretinal membrane, 11 (11%) had vitreomacular traction, 8 (8%) had lamellar macular hole, 5 (5%) had diabetic macular edema, and 5 (5%) had macular pseudohole. The mean age of patients with occult macular pathology was significantly higher than that of patients with normal OCT findings (p=0.001). 78.0% of patients with retinal pathology were 70 years of age or older. Advanced age was identified as the most important predictor of occult macular pathology (OR: 1.086, p=0.001).

CONCLUSION: Reliance solely on fundoscopic examination would result in approximately 1 in 10 eyes with occult macular pathology being overlooked. OCT screening should be considered prior to cataract surgery, particularly in elderly patients.},
}

@article {pmid42549279,
year = {2026},
author = {Cheong, KX and Lan, W and Hoang, QV and Saw, SM},
title = {The prevalence, progression, and visual loss associated with myopic macular degeneration in Asia.},
journal = {Taiwan journal of ophthalmology},
volume = {16},
number = {2},
pages = {272-284},
pmid = {42549279},
issn = {2211-5072},
abstract = {This systematic review examines the epidemiology, natural history, and visual outcomes of myopic macular degeneration (MMD) in Asia. MMD is irreversible, may affect both eyes, and may occur during a person's productive years, making it a significant public health concern. Population-based studies report a wide variation in MMD prevalence, ranging from 0.24% in rural India to 4.5% in mainland China. MMD is etiologically heterogeneous, with its prevalence associated with a more negative spherical equivalent (SE), longer axial length (AL), older age, and a lower education level. The development of MMD is likely nonlinear, with the prevalence of MMD increasing markedly once specific thresholds in age (60-70 years), SE (-6 to - 7 diopters), and AL (about 26 mm) are exceeded. The 5-year, 6-year, and 12-year incidence of MMD is up to 1.1%, 1.2%, and 10.3% respectively. The 10-year progression rate of MMD may reach 35.5%, often involving the development or worsening of chorioretinal atrophy. MMD is associated with significant visual impairment (VI) and blindness, with a decrease in best corrected visual acuity (BCVA) ranging from one to 13 lines. Among individuals with MMD, up to 54.5% experience VI, and up to 14.9% develop blindness in the better eye. Up to 36.4%, 21.6%, 12.3%, and 4.5% of individuals with MMD have unilateral VI, bilateral VI, unilateral blindness, and bilateral blindness, respectively. BCVA loss increases with MMD severity. These findings underscore the urgent need for public health strategies to address the growing burden of MMD in Asia's aging and increasingly myopic populations.},
}

@article {pmid42549844,
year = {2026},
author = {Yu, RMC and Oguz, G and Fu, NY and Shihabuddeen, WA and Cheung, C and Wang, X and Wong, TY and Cheung, CMG and Ramasamy, A and Yanagi, Y},
title = {Caveola and Its Resident Proteins, Caveolin-1 and -2, Play Critical Roles in the Pathogenesis of nAMD and PCV.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {10},
pages = {10},
doi = {10.1167/iovs.67.10.10},
pmid = {42549844},
issn = {1552-5783},
mesh = {Humans ; *Caveolin 1/genetics/physiology/biosynthesis ; *Polypoidal Choroidal Vasculopathy/metabolism/genetics ; *Caveolin 2/genetics/physiology/biosynthesis ; *Caveolae/metabolism ; Female ; Human Umbilical Vein Endothelial Cells/metabolism ; *Macular Degeneration/metabolism/genetics ; Male ; Gene Expression Regulation/physiology ; Cytokines/metabolism ; Monocytes/metabolism ; Leukocytes, Mononuclear/metabolism ; Aged ; },
abstract = {PURPOSE: The purpose of this study was to investigate cellular and molecular mechanisms underlying neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) via single-cell RNA sequencing (scRNA-seq), then focusing on caveolae-resident proteins based on identified negatively enriched caveolae via Gene Set Enrichment Analysis (GSEA).

METHODS: Peripheral blood mononuclear cells (PBMCs) from patients with nAMD/PCV (n = 10) and healthy controls (n = 9) were collected. A total of 22,593 high-quality monocytes were analyzed for differentially expressed genes (DEGs) and GSEA. The key finding of negatively enriched caveola was recapitulated by in vitro mRNA transfections in THP-1 monocytes and human umbilical vein endothelial cells (HUVECs), followed by validation using qPCR. Functional assays and cytokine profiling were also performed.

RESULTS: A total of 122 significant pathways was identified from WikiPathways, Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology. GSEA revealed significant negative enrichment of caveola in classical monocytes of PCV (NES = -1.769, P = 0.001, q = 0.026). Cytokine/chemokine profiling revealed that Caveolin (CAV)1/2-overexpressing monocytes secreted markedly higher levels of several proinflammatory mediators, including IL-1β, IL-2, IL-8, IL-17, TNF-α, PDGF-BB, and MIP-1α/β. CAV1 or CAV2 overexpression in THP-1 cells increased monocyte adhesion but inhibited transendothelial migration. In HUVECs, their overexpression induced moderate cytokine profiles, including downregulation of RANTES (CCL5), IL-10, and VEGF, and upregulation of IL-6 and MIP-1α. CAV1/2 overexpression also significantly inhibited tube formation, whereas knockdown of CAV1 or CAV2 enhanced tube formation.

CONCLUSIONS: Caveolins appear to contribute to the pathogenesis of nAMD and PCV as modulators of inflammation and vascular function. Enhanced CAV1/2 expression in endothelial cells attenuates angiogenic activity, indicating a potential therapeutic strategy.},
}

Humans
*Caveolin 1/genetics/physiology/biosynthesis
*Polypoidal Choroidal Vasculopathy/metabolism/genetics
*Caveolin 2/genetics/physiology/biosynthesis
*Caveolae/metabolism
Female
Human Umbilical Vein Endothelial Cells/metabolism
*Macular Degeneration/metabolism/genetics
Male
Gene Expression Regulation/physiology
Cytokines/metabolism
Monocytes/metabolism
Leukocytes, Mononuclear/metabolism
Aged

@article {pmid42552269,
year = {2026},
author = {Sumer, F and Toren, M and Asan, B and Solak, M and Coskuner, N and Ozkan, B and Karabas, VL and Demirel, S and Ozdemir, H},
title = {Comparative Evaluation of Deep Generative Models for Predicting 12-Month Neovascular AMD Progression Using OCT and Fundus Photography.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
pmid = {42552269},
issn = {2948-2933},
abstract = {The purpose of this study is to systematically compare six deep generative models for predicting long-term anatomic progression of neovascular age-related macular degeneration (nAMD) from pretreatment retinal imaging. We retrospectively analyzed OCT and fundus images from 85 treatment-naïve eyes initiating anti-VEGF therapy for nAMD. Five GAN-based architectures (BiCycleGAN, CycleGAN, Pix2pixHD, CycleGAN-Turbo, Pix2pix-Turbo) and one diffusion-based model (Stable Diffusion Img2Img) were trained separately for each modality to generate synthetic projections at 3, 6, and 12 months. Quantitative performance was assessed using structural similarity index (SSIM), peak signal-to-noise ratio (PSNR), mean squared error (MSE), and root mean squared error (RMSE). Clinical realism was evaluated through a visual Turing test by five blinded expert graders. Pix2pixHD consistently achieved the highest image-quality metrics across all models, modalities, and time points. For OCT, they are SSIM 0.84 and PSNR 27.2 dB (3 months) and SSIM 0.83 and PSNR 25.8 dB (12 months). For fundus photographs, they are SSIM 0.80 and PSNR 26.0 dB (3 months) and SSIM 0.80 and PSNR 24.7 dB (12 months). In the visual Turing test, experts correctly identified synthetic images in 58% of cases (chance level, 50%), with OCT images showing near-chance discriminability (52%) compared to fundus photographs (64%). This study provides the first systematic comparison of multiple generative architectures for long-term nAMD progression prediction. Pix2pixHD achieved the highest fidelity, generating synthetic images whose realism was frequently, though not reliably, distinguished by observers (58%, not significantly different from chance; p = 0.13), particularly for OCT. These findings support the potential of deep generative models for AI-driven decision support in personalized retinal care. This work bridges the gap between computational science and clinical ophthalmology by demonstrating that deep generative models can transform pretreatment retinal images into clinically realistic predictions of disease progression. By enabling visualization of anticipated anatomical outcomes before treatment initiation, these tools have the potential to transition nAMD management from reactive to proactive paradigms, supporting individualized patient counseling, risk stratification, and evidence-based treatment planning at the point of care.},
}

@article {pmid42552408,
year = {2026},
author = {Zhuang, X and Ulla, L and Foti, C and Cariola, R and Neri, G and Olivieri, C and Parisi, G and Petrillo, F and Marolo, P and Reibaldi, M and Borrelli, E},
title = {Real-world comparative effectiveness of faricimab versus aflibercept 2 mg in treatment-naïve exudative neovascular AMD patients treated with a treat-and-extend regimen.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42552408},
issn = {1476-5454},
abstract = {PURPOSE: To compare the real-world effectiveness of faricimab versus aflibercept 2 mg in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

METHODS: We analysed treatment-naïve nAMD patients aged ≥50 years initiating intravitreal anti-VEGF therapy between March 2024 and September 2024. Patients received either faricimab or aflibercept 2 mg. Inverse probability of treatment weighting was used to minimise selection bias. Primary outcomes were best-corrected visual acuity (BCVA) changes from baseline to post-loading phase and 1-year follow-up. Secondary outcomes included anatomic resolution of intraretinal fluid (IRF), subretinal fluid (SRF), and subretinal hyperreflective material (SHRM), treatment burden, and safety.

RESULTS: A total of 172 patients were included (86 faricimab, 86 aflibercept). Baseline characteristics were well-balanced between groups. The faricimab regimen was associated with greater BCVA improvement compared with aflibercept at post-loading phase (adjusted mean difference -0.075 logMAR; 95% confidence interval [CI], -0.130 to -0.020; P = 0.008) and at 1 year (-0.073 logMAR; 95% CI, -0.128 to -0.018; P = 0.011). Patients receiving faricimab achieved significantly higher rates of SRF resolution (odds ratio 2.446; 95% CI, 1.012 to 5.912; P = 0.047). The faricimab group was associated with fewer injections from the post-loading phase to 1 year (median 3 vs. 4; P < 0.001) and lower therapy switching rates (7.9% vs. 25.6%; P = 0.003).

CONCLUSIONS: In treatment-naïve nAMD patients, faricimab achieved greater visual acuity gains, enhanced anatomic outcomes, and reduced treatment burden compared with aflibercept. However, these findings should be interpreted in light of the non-randomised design, different loading regimens, and potential differences in early treatment exposure.},
}

@article {pmid42554417,
year = {2026},
author = {Ford, LM and Occelli, LM and Enfield, ME and Benjamin, NA and Sun, K and Pasmanter, N and Petersen-Jones, SM},
title = {Functional and Structural Characterization of a Large Animal Model of RDH5-Associated Retinopathy.},
journal = {Translational vision science & technology},
volume = {15},
number = {8},
pages = {2},
doi = {10.1167/tvst.15.8.2},
pmid = {42554417},
issn = {2164-2591},
mesh = {Animals ; Disease Models, Animal ; Cats ; *Alcohol Oxidoreductases/genetics/metabolism ; Electroretinography ; Tomography, Optical Coherence ; Ophthalmoscopy ; Retinal Cone Photoreceptor Cells ; Retinal Rod Photoreceptor Cells ; Immunohistochemistry ; Mutation, Missense ; Humans ; Retinal Diseases ; },
abstract = {PURPOSE: Inherited retinal diseases are a group of hereditary diseases that cause variable levels of blindness and affect a multitude of adults and children. One such disease is fundus albipunctatus (FA). FA is caused by autosomal recessive retinol dehydrogenase 5 (RDH5) mutations and results in rod dysfunction leading to night blindness and, in a subset of patients, macular degeneration (MD). We previously reported a spontaneous feline model of FA due to an RDH5 missense mutation. The affected cats showed rod dysfunction and a proportion developed degeneration of the area centralis (AC), equivalent to MD in humans.

METHODS: We used fundus confocal scanning laser ophthalmoscopy and spectral-domain optical coherence tomography imaging, six different electroretinography protocols, immunohistochemistry, and histology/transmission electron microscopy to further characterize this large-animal cat model.

RESULTS: In addition to rod dysfunction, cone recovery from intense stimulation was impaired. For RDH5-/- cats that developed AC degeneration, an initial elongation of rod outer segments with disorganization of the distal tips was initially detected in the AC and visual streak, suggestive of impaired shedding/phagocytosis. With progression, photoreceptors degenerated in the AC, matching the MD seen in some human patients.

CONCLUSIONS: The RDH5-/- cat model recapitulates features of both rod and cone dysfunction seen in human patients with RDH5 mutations.

TRANSLATIONAL RELEVANCE: The RDH5-/- cat model offers a unique opportunity to further understand the mechanisms of RDH5-associated retinopathies and to investigate potential therapeutic approaches.},
}

Animals
Disease Models, Animal
Cats
*Alcohol Oxidoreductases/genetics/metabolism
Electroretinography
Tomography, Optical Coherence
Ophthalmoscopy
Retinal Cone Photoreceptor Cells
Retinal Rod Photoreceptor Cells
Immunohistochemistry
Mutation, Missense
Humans
Retinal Diseases

@article {pmid42555638,
year = {2026},
author = {Liu, X and Tang, D and Zhang, J and Li, T and Huang, J and Qu, J and Ruan, Y and Chai, H and Chi, ZL},
title = {3D epigenomic landscape of the human retinal pigment epithelium.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {32},
pages = {e2526200123},
doi = {10.1073/pnas.2526200123},
pmid = {42555638},
issn = {1091-6490},
support = {82271114//MOST | National Natural Science Foundation of China (NSFC)/ ; 32250710678//MOST | National Natural Science Foundation of China (NSFC)/ ; 32400426//MOST | National Natural Science Foundation of China (NSFC)/ ; LZ22H120001//MOST | NSFC | NSFC-Zhejiang Joint Fund | | Natural Science Foundation of Zhejiang Province (ZJNSF)/ ; KYYW202227//Wenzhou Medical University (WMU)/ ; YNZD1201901//Eye Hospital Wenzhou Medical University/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/cytology ; *Epigenomics/methods ; Induced Pluripotent Stem Cells/metabolism/cytology ; Cell Differentiation ; Chromatin/metabolism/genetics ; Extracellular Matrix/metabolism ; Cell Line ; *Epigenesis, Genetic ; },
abstract = {The retinal pigment epithelium (RPE) is crucial for visual function, and its dysfunction contributes to retinal diseases such as age-related macular degeneration. Despite the translational potential of iPSC-derived RPE (iPSC-RPE) in cell replacement therapy, the functional visual gains achieved to date are modest. A key challenge is that the molecular and epigenomic signatures underlying functional RPE are yet to be fully elucidated. By integrating multiomics data, we systematically benchmarked the 3D epigenomic landscapes of primary human RPE (hRPE), iPSC-RPE, and the immortalized ARPE-19 cell line. Our analysis reveals that iPSC-RPE exhibits a mixed molecular state. iPSC-RPE recapitulates hRPE-like transcription and chromatin looping, but its histone modification states remain incompletely matured, and its chromatin accessibility and higher-order chromatin organization do not fully converge to hRPE. Furthermore, we found that hRPE exhibits strong extracellular matrix (ECM) organization driven by enhancer-mediated long-range chromatin interactions and enriched RUNX1 motifs, while iPSC-RPE retains key developmental-related transcriptional signatures, marked by factors such as HAND1, OTX2, and PAX6. These findings establish a multiomics benchmark for RPE maturity, pinpoint key regulatory nodes like ECM organization and RUNX1 for therapeutic targeting, and provide a roadmap for optimizing differentiation protocols and scaffold design in retinal regenerative medicine.},
}

Humans
*Retinal Pigment Epithelium/metabolism/cytology
*Epigenomics/methods
Induced Pluripotent Stem Cells/metabolism/cytology
Cell Differentiation
Chromatin/metabolism/genetics
Extracellular Matrix/metabolism
Cell Line
*Epigenesis, Genetic

@article {pmid42556322,
year = {2026},
author = {Pizzato, HA and Bhattacharya, D},
title = {Guiding pluripotent stem cell therapies past the immune system.},
journal = {Stem cells translational medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.1093/stcltm/szag051},
pmid = {42556322},
issn = {2157-6580},
support = {R41AI191979/NH/NIH HHS/United States ; R41AI192172/NH/NIH HHS/United States ; },
mesh = {Humans ; *Pluripotent Stem Cells/immunology/transplantation ; Animals ; *Diabetes Mellitus, Type 1/therapy/immunology ; *Stem Cell Transplantation/methods ; *Graft Rejection/immunology/prevention & control ; *Immune System ; },
abstract = {Pluripotent stem cell (PSC)-based therapies hold the potential to unlock cures for numerous diseases, including, but not limited to, Parkinson's disease, macular degeneration, heart failure, type 1 diabetes, and cancer. Yet as protocols to differentiate PSCs into therapeutically useful cell types have progressed rapidly, immunological rejection remains a major barrier that may limit the widespread use of such PSC-based therapies. In recent years, strategies to genetically modify PSCs to prevent immunological rejection of the downstream cell product have become a point of emphasis. Here, we provide an immunological perspective on these strategies, discussing the breadth of rejection mechanisms that have been uncovered through decades of research and the relative simplicity of designing PSC immune evasion strategies to circumvent these mechanisms. We focus in particular on how these strategies apply to the treatment of type 1 diabetes.},
}

Humans
*Pluripotent Stem Cells/immunology/transplantation
Animals
*Diabetes Mellitus, Type 1/therapy/immunology
*Stem Cell Transplantation/methods
*Graft Rejection/immunology/prevention & control
*Immune System

@article {pmid42556705,
year = {2026},
author = {Holekamp, NM and Ivanova, S},
title = {The Perfusion-Based Model of AMD: Moving Towards a Unifying Hypothesis.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101507},
doi = {10.1016/j.preteyeres.2026.101507},
pmid = {42556705},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) is a complex disease wherein age, genetics, and environment play a role. How each of these factors contribute to the overall disease initiation and progression remains largely unelucidated. A renewed examination of the existing literature regarding the blood supply to the outer retina may provide novel insights. Hypoxia in the retinal pigment epithelium (RPE) can produce features of AMD, including photoreceptor degeneration. In the macula, the choriocapillaris has unique features making it susceptible to hypoperfusion, producing low-grade ischemia and chronic tissue hypoxia. The choriocapillaris experiences vascular loss and decreased blood flow early in AMD. Genetic risk, when viewed through a new lens, points to vascular insult as central to AMD pathophysiology. Complement-related risk genes are active in the vasculature, from large tributary vessels to small vessels of the choriocapillaris. HtrA serine peptidase 1 (HTRA1) is associated with cerebral small vessel disease and localizes to the choriocapillaris in AMD. Ageing can be interpreted as inevitable atherosclerosis from large to small vessels of the cerebral system. Western diets, smoking, and a rising prevalence of metabolic syndrome in people over age 60 are confirmed to accelerate both atherosclerosis and AMD. A perfusion-based model for complement-related, soft drusen-associated AMD is proposed while also explaining a second phenotype of non-complement related subretinal drusenoid deposit-associated AMD. Common to both phenotypes of AMD is chronic hypoperfusion causing decreased oxygen exchange and waste removal at the neurovascular unit of the choriocapillaris, RPE, and photoreceptors. Understanding AMD as an end-organ vascular disease may move us towards a unifying hypothesis.},
}

@article {pmid42556869,
year = {2026},
author = {Wilkinson, E and Beresford, S and Mushtaq, B and Salvatore, S and Sivaprasad, S and Brown, K and Carter, JS and Singh, J and Schrire, T and Chase, TJG},
title = {Optimising the patient pathway for macular conditions requiring intravitreal injections.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {3},
pages = {},
doi = {10.1136/bmjophth-2025-002663},
pmid = {42556869},
issn = {2397-3269},
mesh = {Humans ; Intravitreal Injections ; *Angiogenesis Inhibitors/administration & dosage ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Retinal Vein Occlusion/drug therapy ; Macular Edema/drug therapy ; *Macular Degeneration/drug therapy ; *Critical Pathways ; },
abstract = {Macular disease is the leading cause of vision loss in the United Kingdom, affecting nearly 1.5 million people. Vascular endothelial growth factor (VEGF) has a major role in the onset and progression of vision-threatening macular conditions such as neovascular age-related macular degeneration, diabetic macular oedema and retinal vein occlusion. Anti-VEGF treatments, given by intravitreal injection, can prevent vision loss and may improve vision but must be started quickly before sight loss is irreversible. Informed by an observational study using Hospital Episode Statistics and the Emergency Care Data Set in England and a Costed Integrated Patient Scenario, we identify issues within the current pathway in England. Our key recommendations to optimise care and improve patient outcomes include: (1) increasing public awareness of macular disease to reduce late presentation; (2) ensuring the right patients are seen in the right place at the right time by improving quality and priority of optometrist referrals and by specialists directing patients with conditions such as diabetes and hypertension to community optometrists in the first instance; (3) planning for current and future demand and capacity using innovative solutions to manage expected increases in medical retina conditions and (4) ensuring patient-centred care. Our evidence should encourage National Health Service organisations at all levels to review macular disease pathways to address immediate issues and plan for the future. A shift in care delivery is needed, embracing scalable sustainable solutions, earlier diagnosis and treatment, improved access to more durable therapies, wider adoption of digital technologies and care closer to home.},
}

Humans
Intravitreal Injections
*Angiogenesis Inhibitors/administration & dosage
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Retinal Vein Occlusion/drug therapy
Macular Edema/drug therapy
*Macular Degeneration/drug therapy
*Critical Pathways

@article {pmid42557039,
year = {2026},
author = {Lin, Z and Wang, S and You, R and Wang, L and Abdullahi, MA and Du, W and Xu, X and Lu, F and Zhang, S and Liang, Y},
title = {Integrating opportunistic ocular diseases screening into general health examination in Chinese: a multicentre study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329267},
pmid = {42557039},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: Cost-effective screening models for ocular diseases in large populations remain a critical challenge for blindness prevention. Our preliminary study demonstrated the feasibility of opportunistic glaucoma screening integrated into general health examinations. This study aimed to evaluate the efficacy of this model for fundus disease screening in a multicentre, large-sample Chinese population.

METHODS: This study was conducted in five health examination centres from four provinces of China. Chinese participants aged ≥18 years undergoing routine health examinations were invited to complete bilateral presenting visual acuity and non-mydriatic fundus photography. Fundus photography was assessed by two experienced graders. Proportion of fundus diseases/changes were calculated. Costs for the screening were also assessed.

RESULTS: A total of 63 935 eligible participants (age 45.4±14.0 years, 51.3% men) were enrolled. The top five diseases/changes were non-macular drusen (8.80%), macular degeneration (6.30%), glaucoma suspect (5.54%), epiretinal membrane (3.92%) and diabetic retinopathy (3.89%). The proportion of low vision and blindness in the total population was 5.85% and 0.15%, respectively. The top five diseases/changes with vision impairment were retinitis pigmentosa (18.18%), myopic retinopathy (16.52%), macular hole (11.76%), non-glaucomatous optic neuropathy (7.25%) and glaucomatous optic neuropathy (6.37%). The unit cost of screening a single case and an ocular disease suspect was US$22.2 (US$15.7 to US$26.7) and US$83.2 (US$58.7 to US$99.9), respectively.

CONCLUSIONS: This health examination centre-based screening model is feasible, effective and affordable for detecting multiple fundus diseases in large populations. As the model is promoted and its coverage expands, screening costs may be further reduced.},
}

@article {pmid42557420,
year = {2026},
author = {Velez-Montoya, R and Cruz-Gonzalez, A and Pedraza-Rivera, G and García-Albisua, AM and Ureña-Tejeda, KM and Rosales-Díaz, R and Lucero-De la Rosa, X and Pineda-Pérez, JE and Hernández-Castellanos, S and Guevara-Flores, K and Ramirez-Estudillo, A and Campos-Wolter, CI and Marte-Ramirez, VA and Ledesma-Gil, G and Navas, A and González-Cortés, JH and Mohamed-Noriega, K and Ramos-Betancourt, N},
title = {Ocular surface and meibomian gland changes following repeated exposure to 5% povidone-iodine during intravitreal injections.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42557420},
issn = {1476-5454},
abstract = {BACKGROUND: To evaluate the impact of repeated exposure to 5 percent povidone iodine on meibomian gland atrophy in eyes receiving intravitreal injections.

METHODS: Patients undergoing intravitreal injections with a standardised protocol that included 5% povidone-iodine instillation in one eye were prospectively enroled. Eligible patients had received their last injection within the previous 12 weeks. Patients were stratified according to the number of prior injections. Those with systemic conditions or medications affecting ocular surface parameters were excluded. Assessments included Keratograph 5 M meibography, slit lamp examination, and Schirmer testing at baseline, one hour, and seven days after injection. Meibomian gland atrophy was quantified using ImageJ software. Statistical analysis included repeated-measures ANOVA, regression modelling, and interobserver agreement.

RESULTS: A total of 143 patients with a mean age of 69 years were included. Age-related macular degeneration was the predominant diagnosis, and treat and extend was the most common protocol. In the study eye, tear meniscus height, bulbar hyperaemia, and Schirmer scores increased, while tear breakup time decreased at one hour post-injection. These changes were most evident in patients with fewer than five or more than thirteen prior injections and resolved by day seven. Meibography revealed reduced gland atrophy, especially in the inferior eyelid. Regression analysis showed a small but significant inverse association between injection number and gland atrophy.

CONCLUSIONS: Patients with more intravitreal injections and greater exposure to 5% povidone-iodine showed less meibomian gland atrophy, particularly in the inferior eyelid, along with improved ocular surface parameters.},
}

@article {pmid42558051,
year = {2026},
author = {Mohapatra, D and Corson, TW},
title = {Diagnostic and therapeutic potential of carbon nanodots for ocular disease.},
journal = {Nanomedicine (London, England)},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/17435889.2026.2712542},
pmid = {42558051},
issn = {1748-6963},
abstract = {Conventional therapeutics (eye drops, injectables, ointments, gels) for ocular diseases face several challenges, including low ocular permeability, rapid clearance, low bioavailability, and off-target effects due to complex anatomical barriers and physiological ocular events. Nanomedicine can avoid some challenges of conventional delivery systems by offering prolonged ocular retention, site-specific targeted drug delivery, low toxicity, improved bioavailability, and therapeutic activity. Further, theranostic nanomedicines offer the advantages of diagnostic and therapeutic features during treatment. Carbon dots (CDs), also known as carbon nanodots (CNDs) or carbon quantum dots (CQDs), are ultra-low-sized, zero-dimensional nanomaterials with a diameter below 10 nm, and have received attention due to their excellent fluorescence, tunable emission, biocompatibility, aqueous solubility, surface functionalization ability, stability, safety, and cost-effectiveness. A growing number of studies explore the therapeutic, diagnostic, or theranostic use of CDs for ocular applications, demonstrating real-time monitoring of disease progression and treatment efficacy in ocular disease models. CDs have been explored for ocular drug delivery, fluorescent angiography, ocular bioimaging, and treatment in models of various ocular diseases, including bacterial keratitis, glaucoma, vitreous opacification, and neovascular age-related macular degeneration (nAMD). In this special report, the potential of CDs for ophthalmic applications is reviewed based on publications over the last decade.},
}

@article {pmid42546222,
year = {2026},
author = {Pyatova, Y and Zhang, B and Misawa, M and Markowitz, SN and Sen, A and Appel, L and Cheung, K and Nasir, P and Tchao, D and Garcia-Giler, E and Daibert-Nido, M and Reber, M},
title = {A Visual Telerehabilitation Program in Virtual Reality for Age-Related Macular Degeneration: Randomized Feasibility and Proof-of-Concept Trial.},
journal = {JMIR rehabilitation and assistive technologies},
volume = {13},
number = {},
pages = {e87596},
pmid = {42546222},
issn = {2369-2529},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) causes progressive central vision loss in older adults. Low-vision rehabilitation can improve functional vision by training the use of a preferred retinal locus, commonly through clinic-based biofeedback training (BFT). However, repeated supervised rehabilitation is burdensome, and functional gains may be difficult to sustain without home practice. Stand-alone virtual reality (VR) may enable home-based, remotely monitored visual stimulation, but feasibility, safety, and usability in older adults with AMD remain insufficiently characterized.

OBJECTIVE: This study aimed to evaluate the feasibility and safety of adding home-based VR 3D single-object tracking (3D-SOT-VR) to conventional BFT in older adults with dry AMD in a parallel, randomized, single-blind (to assessors), controlled, formative trial and to generate exploratory functional hypotheses for a future trial.

METHODS: Adults with dry AMD were recruited at the Low Vision Clinic, Toronto Western Hospital, University Health Network, Toronto, Ontario, Canada, from September 2021 to October 2023. Participants were randomized to BFT once weekly for 4 weeks (BFT group) or BFT plus home-based 3D-SOT-VR (BFT-VR group) every other day for 4 weeks. Experimental intervention consisted of tracking a single object among distractors moving at different speeds in a 3D virtual space in a VR headset. Primary feasibility and safety outcomes included recruitment, adoption, adherence, compliance, intervention completion, remote data transfer, usability, and VR-induced symptoms and effects. Secondary outcomes included visual acuity, contrast sensitivity, fixation stability, retinal sensitivity, reading speed, and low-vision quality of life. Exploratory outcomes assessed performance at 3D-SOT-VR and usage. Analyses were descriptive and exploratory, with CIs and denominators reported to reflect limited precision and missingness.

RESULTS: Fourteen individuals were randomized (BFT, n=6; BFT-VR, n=8), below the planned sample size of 32. Recruitment was not achieved because of COVID-19-related interruptions and reduced onsite access. Eleven individuals were analyzed for the primary outcome (BFT n=6, BFT-VR n=5). Intervention completion was 100% in the BFT arm and 75% in the BFT-VR arm, below the prespecified BFT-VR threshold. Among participants who used VR, adherence to scheduled home sessions was acceptable, completed VR-session files were transmitted without loss, and no participant met the predefined cybersickness stopping rule. One BFT-VR participant discontinued because headset weight caused neck fatigue. Group-level visual outcomes did not provide significant effectiveness. Reading speed showed a clinically meaningful individual-level improvement in the BFT-VR arm and correlated with VR-task performance. The findings were not clearly durable at follow-up.

CONCLUSIONS: This pilot study provides formative evidence that clinic-based BFT combined with home-based, remotely monitored VR visual stimulation can be implemented safely in older adults with dry AMD, while identifying major contextual feasibility barriers. The intervention is innovative because it extends low-vision rehabilitation into the home using a connected device and objective performance monitoring. Recruitment, retention, missing data handling, and sustainability of functional gains must be addressed before effectiveness testing.},
}

@article {pmid42546865,
year = {2026},
author = {Jonas, JB and Jonas, RA and Wang, YX and Panda-Jonas, S},
title = {Central Retinal Vessel Trunk Dragging in Highly Myopic Eyes.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.07.058},
pmid = {42546865},
issn = {1879-1891},
abstract = {PURPOSE: To assess occurrence and associations of central retinal vessel trunk (CRVT) dragging.

DESIGN: Retrospective, population-based cohort study.

METHODS: Using optical coherence tomographic images of the optic disc and macula, taken in the participants of the Beijing Eye Study, we assessed the prevalence of CRVT-dragging, defined as an optic disc tissue prominence at the inferior, superior and nasal, but not the temporal, optic disc border.

RESULTS: The study included 3336 individuals (3336 eyes) (mean age:64.2±9.6 years; axial length:23.4±1.2mm (range:20.16-30.88mm). CRVT dragging prevalence increased from 0/3046 (0%) to 9/173 (5.2%;95%CI:2,9), 9/74 (12.2%;95%CI:5,20), 6/25 (24.0%;95%CI:6,42) and to 13/18 (72.2%;95%CI:49,95) in eyes with an axial length of ≤25.0mm, 25.01mm-26.0mm, 26.01mm-27.0mm, 27.01mm-28.0mm, and >28.0mm, respectively. Higher CRVT dragging prevalence was associated (multivariable analysis) with longer optic disc-fovea distance (OR:5.82;95%CI:2.23,15.2;P<0.001) and higher prevalence of parapapillary retinoschisis (OR:8.61;95%CI:2.43,30.5;P<0.001), with adjusting for longer axial length (OR:1.95;95%CI:1.25,3.05;P=0.003) and older age (OR:1.08;95%CI:1.02,1.14;P=0.008). In eyes with an axial length of ≥25.0 mm, CRVT dragging prevalence increased 5.69-fold (95% CI:2.30,14.1) for each mm increase in fovea-disc distance. These relationships were complemented by univariate associations between CRVT dragging prevalence and temporal retinal vessel straightening, smaller angle kappa, higher myopic macular degeneration stage and prevalence, and larger parapapillary beta zone and gamma zone.

CONCLUSIONS: CRVT-dragging as a common feature in highly myopic eyes may etiologically be explained by the myopic axial elongation-related increase in the fovea-disc distance. Influencing the three-dimensional appearance of the optic nerve head, CRVT dragging may be of importance for the morphological diagnosis of optic neuropathies in highly myopic eyes.},
}

@article {pmid42547533,
year = {2026},
author = {Chauhan, MZ and Muayad, J and Karimaghaei, C and Karimaghaei, S and Sallam, AB},
title = {Large-scale analysis of risk factors for developing retinal vein occlusion in the fellow eye.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42547533},
issn = {1476-5454},
abstract = {BACKGROUND/OBJECTIVES: The main objective was to elucidate the associations for developing a fellow-eye retinal vein occlusion (RVO) after a patient experiences a first-time unilateral RVO event.

SUBJECTS/METHODS: Large, multicenter, retrospective study using the global TriNetX database. We included patients newly diagnosed with unilateral RVO from 1 January 2015 to 1 January 2025. We estimated the incidence of fellow-eye RVO using Kaplan-Meier survival analysis, compared baseline demographic and medical characteristics between groups with and without progression to bilateral RVO and calculated hazard ratios with 95% confidence intervals for fellow-eye RVO based on various systemic and ocular comorbidities.

RESULTS: 437 of 22,969 patients (1.90%) developed RVO in the fellow eye. Patients with fellow-eye RVO had higher rates of primary open-angle glaucoma (POAG; 22% vs. 17%, p = 0.006), dry age-related macular degeneration (AMD; 15% vs. 12%, p = 0.008) and anemia (39% vs. 31%, p = 0.0001). They also were more likely to self-identify as Black/African American (21% vs. 17%, p = 0.03) and less likely to be White (50% vs. 58%, p = 0.0008). No significant difference was identified between mean age, sex, or rates of traditional cardiovascular risk factors across these two groups. There was a 1.41- (95% CI 1.03-1.94), 1.46- (95% CI 1.02-2.10) and 1.84-fold (95% CI 1.38-2.47) increased hazard of developing bilateral sequential RVO with baseline POAG, dry AMD and anemia, respectively.

CONCLUSION: The presence of primary open-angle glaucoma, dry age-related macular degeneration and anemia is significantly associated with fellow-eye RVO and may help prognosticate the development of progressive disease in patients with unilateral RVO.},
}

@article {pmid42540322,
year = {2026},
author = {Mohapatra, D and Seo, SY and Corson, TW},
title = {Development and characterization of a topical ferrochelatase inhibitor nanoemulsion for choroidal neovascularization therapy.},
journal = {International journal of pharmaceutics: X},
volume = {12},
number = {},
pages = {100619},
pmid = {42540322},
issn = {2590-1567},
abstract = {Choroidal neovascularization (CNV) is a hallmark of neovascular age-related macular degeneration (nAMD). We previously identified the heme synthesis enzyme ferrochelatase (FECH) as a promising therapeutic target. This study aimed to develop and characterize topical ophthalmic nanoemulsions (NEs) of a novel FECH inhibitor, SH-17023, for CNV therapy, to avoid the intravitreal injections needed for standard-of-care anti-vascular endothelial growth factor (anti-VEGF) biologics. SH-17023-loaded NEs were prepared by spontaneous emulsification and optimized using D-optimal mixture design-based Quality-by-Design to obtain nanometric globule size (Zavg), low polydispersity index (PDI), and highest drug loading capacity (% LC). Therapeutic efficacy was assessed in the laser-induced CNV (L-CNV) mouse model with fundus imaging, optical coherence tomography (OCT), fluorescein angiography, and ex vivo vasculature staining. The optimized formulation was transparent with a globule size of 32.832 ± 2.125 nm, PDI 0.201 ± 0.003, spherical morphology, and LC of 7.436 ± 0.035%. It showed zeta potential of -29.2 ± 0.45 mV, sustained drug release, and robust accelerated and kinetic stability. Attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray diffraction revealed excellent drug-excipient compatibility. Ex vivo goat cornea permeation of NEs showed significantly higher drug transport (permeability coefficient (Kp) = 0.050 ± 0.012 h[-1].cm[-2], steady-state flux (Jss) = 37.51 ± 9.29 μg.h[-1].cm[-2]) than the drug in solution (Kp = 0.002 ± 0.0004 h[-1].cm[-2] and Jss = 1.575 ± 0.488 μg.h[-1].cm[-2]) with an enhancement ratio of 23.815. Optimized NEs significantly reduced L-CNV assessed by OCT and ex vivo staining by >45% compared to blank NEs, without ocular irritation or toxicity, indicating their promise for nAMD therapy.},
}

@article {pmid42541268,
year = {2026},
author = {Vingopoulos, F and Stevanovic, M and Razavi, P and Romano, F and Ding, X and Rodriquez, J and Baldwin, G and Choi, H and Katz, R and Husain, D and Kim, LA and Miller, JW and Vavvas, DG and Miller, JB},
title = {Geographic Atrophy Size Progression Correlates Better with Longitudinal Changes in Quantitative Contrast Sensitivity than Visual Acuity.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101206},
pmid = {42541268},
issn = {2666-9145},
abstract = {PURPOSE: Investigate the cross-sectional and longitudinal correlations between total geographic atrophy (GA) size and quantitative contrast sensitivity function (qCSF).

DESIGN: Prospective, cross-sectional, and longitudinal observational study between November 2018 and March 2023 at Massachusetts Eye and Ear.

SUBJECTS: A total of 83 foveal involving GA eyes cross-sectionally and 30 foveal involving GA eyes longitudinally.

METHODS: Contrast sensitivity (CS) was measured with the qCSF device along with same day spectral-domain OCT and fundus autofluorescence (FAF). Geographic atrophy was defined as hypoautofluorescent lesions on FAF corresponding to complete retinal pigment epithelium and outer retinal atrophy on spectral-domain OCT. Total GA size was measured on FAF using the semiautomatic Heidelberg Region Finder tool. Mixed-effects multivariate regression models were performed to evaluate correlations between GA size, qCSF metrics, and visual acuity (VA).

MAIN OUTCOME MEASURES: Total GA size, longitudinal changes in total GA size, qCSF outcomes (area under the logarithm of contrast sensitivity function [AULCSF], low contrast VA [LCVA], CS thresholds at 1-18 cycles per degree [cpd]), and longitudinal changes in qCSF outcomes.

RESULTS: Cross-sectionally (n = 83), total GA was associated with multiple qCSF outcomes including AULCSF and CS thresholds at 1, 1.5, 3, 6, and 12 cpd (β = -0.23 to -0.39, all P < 0.05), but was not associated with VA (β = 0.08, P = 0.47). At 17.2 months follow-up (range: 6-37) (n = 30), an average increase of 1 mm[2] in total GA size was associated with a nonstatistically significant decrease of 0.01 in VA (P = 0.88), but a statistically significant decrease in CS (-0.05 for AUCLSF, -0.05 for LCVA, -0.04 for 1 cpd, -0.05 for 1.5 cpd, and -0.06 for 3 cpd, all P < 0.05). Standardized regression coefficients suggest that the statistically significant decrease in CS metrics per mm[2] of GA size increase are 11-fold to 20-fold bigger compared to the nonstatistically significant decrease in VA (-0.33 to -0.62 for qCSF versus -0.03 for VA).

CONCLUSIONS: Total GA and longitudinal change in GA size were found to be associated with significant changes in qCSF CS, but not with VA or change in VA. Contrast sensitivity seems to be a better functional endpoint to measure treatment effects in GA.

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

@article {pmid42544414,
year = {2026},
author = {Sevugamurthi, K and Sivashanmugam, P and Jaju, S and Janani, PS and Sakthivel, V and Kumar, N and Elamurugan, V and Pandian, J and Amarakoon, S and Berendschot, TTJM and Narendran, S},
title = {Evaluating the impact of blue-filtering intraocular lenses on macular oxidative stress: A comparative analysis of 8-hydroxy-2'-deoxyguanosine levels in the retinal tissue of donor eyes.},
journal = {Indian journal of ophthalmology},
volume = {74},
number = {Suppl 2},
pages = {S215-S220},
doi = {10.4103/IJO.IJO_3121_25},
pmid = {42544414},
issn = {1998-3689},
mesh = {Humans ; *Oxidative Stress ; Male ; Female ; *8-Hydroxy-2'-Deoxyguanosine/metabolism ; Cross-Sectional Studies ; *Tissue Donors ; Middle Aged ; *Lenses, Intraocular ; Aged ; *Retinal Pigment Epithelium/metabolism ; Enzyme-Linked Immunosorbent Assay ; Blue Light ; *Macula Lutea/metabolism/pathology ; *Deoxyguanosine/analogs & derivatives/metabolism ; Adult ; Biomarkers/metabolism ; },
abstract = {PURPOSE: To evaluate the impact of blue-filtering intraocular lenses (BFIOLs) on retinal oxidative stress by comparing 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in the macular retina and submacular retinal pigment epithelium (RPE) of donor eyes with BFIOLs and non-BFIOLs.

DESIGN: Cross-sectional laboratory study using postmortem human donor eyes.

METHODS: Fifty-eight eyes from 39 donors were categorized as BFIOL (n = 16), non-BFIOL (n = 24), or phakic (n = 18). Macular retina and submacular RPE were dissected, genomic DNA extracted, and 8-OHdG quantified using ELISA. 8-OHdG levels were compared across lens groups, and associations with age and sex were examined.

RESULTS: Submacular RPE had higher 8-OHdG levels than the macular retina (0.95 vs 0.44 ng/mL; P < 0.0001). No significant differences in 8-OHdG were observed between BFIOL and non-BFIOL eyes in either tissue (all P ≥ 0.09). Age was not associated with 8-OHdG, whereas male donors showed higher RPE 8-OHdG levels than female donors (P = 0.03).

CONCLUSIONS: Macular retinal and RPE 8-OHdG levels did not differ significantly by IOL type. These biochemical observations, considered alongside existing clinical data, suggest that any retinal protective effect of BFIOLs on oxidative DNA damage is likely to be modest.},
}

Humans
*Oxidative Stress
Male
Female
*8-Hydroxy-2'-Deoxyguanosine/metabolism
Cross-Sectional Studies
*Tissue Donors
Middle Aged
*Lenses, Intraocular
Aged
*Retinal Pigment Epithelium/metabolism
Enzyme-Linked Immunosorbent Assay
Blue Light
*Macula Lutea/metabolism/pathology
*Deoxyguanosine/analogs & derivatives/metabolism
Adult
Biomarkers/metabolism

@article {pmid42544785,
year = {2026},
author = {Sutinen, P and Hecht, I and Tuuminen, R},
title = {Early high-dose aflibercept 8 mg clinical outcomes in wet age-related macular degeneration patients resistant to aflibercept 2 mg or faricimab.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70213},
pmid = {42544785},
issn = {1755-3768},
}

@article {pmid42537924,
year = {2026},
author = {Xu, S and Zhuo, Q and Li, J and Li, B and Zhu, W and Xue, Y and Zhang, S and Zhao, C},
title = {EV30 suppresses choroidal neovascularization associated with modulation of the mTOR/NF-κB/p38 MAPK signaling pathway.},
journal = {Microvascular research},
volume = {},
number = {},
pages = {104992},
doi = {10.1016/j.mvr.2026.104992},
pmid = {42537924},
issn = {1095-9319},
abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of irreversible vision loss characterized by pathological choroidal neovascularization (CNV). While anti-VEGF therapies are the standard of care, limitations such as treatment resistance and side effects necessitate novel therapeutic agents. This study evaluates the therapeutic efficacy and mechanism of EV30, a novel pterostilbene derivative, in suppressing CNV. EV30 was synthesized based on the pterostilbene template. In vitro, the effects of EV30 on human umbilical vein endothelial cells (HUVECs) proliferation, migration, and tube formation were assessed using Cell Counting Kit-8 (CCK-8), scratch wound, and tube formation assays, respectively. Mechanistic pathways were investigated via Western blotting and RT-qPCR. In vivo, a laser-induced CNV mouse model was treated with intravitreal EV30. Efficacy was evaluated utilizing fundus photography, fluorescein angiography (FFA), optical coherence tomography (OCT), and choroidal flat mounts (IB4 staining). Finally, biosafety was assessed through histology (H&E), electroretinography (ERG), and blood analysis. EV30 demonstrated potent anti-angiogenic properties in vitro, significantly inhibiting HUVEC proliferation, migration, and tube formation in a dose- and time-dependent manner. EV30 reduced vascular endothelial growth factor A (VEGFA) expression and modulated the phosphorylation status of proteins associated with the mTOR/NF-κB/p38 MAPK signaling pathway. In the laser-induced CNV model, EV30 effectively reduced lesion area and vascular leakage comparable to bevacizumab. Furthermore, ERG analysis revealed that EV30 partially preserved retinal electrophysiological function, as indicated by improved scotopic a-wave amplitudes, suggesting functional protection of the retina in the CNV model. EV30 exerted anti-angiogenic effects and was associated with modulation of mTOR/NF-κB/p38 MAPK signaling activity. Together, these findings suggest that EV30 represents a potential therapeutic candidate for CNV by suppressing pathological angiogenesis and modulating inflammation-associated signaling pathways.},
}

@article {pmid42537985,
year = {2026},
author = {Li, X and Gui, F and Zheng, Z and Shi, K},
title = {Cell-state-resolved transcriptomic analysis reveals macrophage-centered pyroptosis-related inflammatory programs in age-related macular degeneration.},
journal = {SLAS technology},
volume = {},
number = {},
pages = {100456},
doi = {10.1016/j.slast.2026.100456},
pmid = {42537985},
issn = {2472-6311},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is accompanied by inflammatory changes in the retinal pigment epithelium/choroid complex, but the cellular sources of pyroptosis-related transcriptional programs in human AMD tissue remain unclear. This study profiled these programs at single-cell resolution and explored candidate regulatory molecules.

METHODS: We analyzed the human retinal pigment epithelium (RPE)/choroid single-cell RNA-sequencing dataset GSE135922 to define cell clusters, pyroptosis-related genes, and regulons. AUCell was applied to estimate pyroptosis-related signature activity in individual cell types. The macrophage cluster with the highest score was examined by pathway enrichment, subclustering, and Monocle 2 pseudo-time analysis, and SCENIC-based regulon analysis was used to infer candidate transcriptional regulators. Pyroptosis-related genes and transcription factors were also evaluated in T-cell, endothelial-cell, and fibroblast subclusters. Bulk RNA sequencing and immunofluorescence in a laser-induced choroidal neovascularization (CNV) mouse model were used for supportive evidence.

RESULTS: Across human RPE/choroid cell clusters, 60 cluster-specific pyroptosis-related marker genes were detected. At the cell-type ranking level, macrophages, T cells, endothelial cells, and fibroblasts showed relatively higher pyroptosis-related signature activity across clusters, with the highest signal in Macrophages-2 and lower activity in RPE cells. Marker genes of Macrophages-2 were enriched in immune and inflammatory pathways, including complement and coagulation cascades, NOD-like receptor signaling, and NF-κB signaling. Pseudo-time analysis resolved Macrophages-2 into divergent trajectories, and NLRP3 was enriched in one post-branch state, consistent with macrophage state heterogeneity rather than uniform activation. IRF1, STAT3, and NEAT1 recurred in cell-type-specific analyses, and Irf1/Stat3 protein signals were higher in CNV lesions.

CONCLUSION: These findings indicate a macrophage-centered, cell-state-specific pattern of pyroptosis-related inflammatory remodeling in AMD. Branch-associated NLRP3 inflammasome signatures, together with IRF1, STAT3, and NEAT1, define candidate molecular features that warrant further mechanistic evaluation.},
}

@article {pmid42538141,
year = {2026},
author = {Meng, J and Zhang, Y and Pei, Y and Kang, C and Cheng, K and Qi, J and He, W and Zhang, K and Lu, Y and Zhu, X},
title = {Transcranial magnetic stimulation as a novel therapeutic approach for severe retinal degenerative diseases: a pilot study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329114},
pmid = {42538141},
issn = {1468-2079},
abstract = {BACKGROUND: Retinal degenerative diseases, including myopic macular degeneration (MMD) and retinitis pigmentosa (RP), lead to irreversible vision impairment, with limited treatment options. Transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique for rehabilitation, may hold potential for vision restoration. The pilot study explored whether TMS is associated with short-term functional visual improvements in patients with severe retinal degenerative diseases.

METHODS: This prospective, non-randomised, parallel-arm pilot study enrolled 98 patients with bilateral severe MMD or RP. Participants received either five consecutive days of theta-burst TMS or conventional conservative care. Primary outcomes were changes in best-corrected visual acuity (BCVA) and visual field from baseline to 4-week follow-up. Contrast sensitivity, macular sensitivity, fixation stability, Visual Function Index-14 (VF-14) and Visual Functioning Questionnaire-25 (VFQ-25) questionnaires were also evaluated. A subset of participants underwent resting-state functional magnetic resonance imaging (fMRI) to explore cortical functional changes.

RESULTS: The study analysed 174 eyes from 88 patients (mean age: 60.3±9.1 years; 52% female). Compared with controls, the TMS group showed greater improvements in BCVA (MMD: 0.22±0.28 logarithm of the minimum angle of resolution (logMAR); RP: 0.24±0.21 logMAR) and VF mean defect (MMD: 1.96±2.09 dB; RP: 1.08±1.28 dB). Contrast sensitivity, macular sensitivity and fixation stability also showed short-term gains. Patient-reported outcomes improved in several functional domains. fMRI demonstrated increased activity and functional connectivity in visual-related cortical regions following TMS.

CONCLUSIONS: In this exploratory pilot study, TMS treatment was associated with short-term functional visual improvements and cortical modulation in individuals with severe retinal degenerative diseases. These findings are hypothesis-generating and warrant validation through larger, randomised, masked clinical trials with longer follow-up.},
}

@article {pmid42538387,
year = {2026},
author = {She, W and She, M and Sun, T},
title = {Comment on: 'Systemic prostacyclin analogues in pulmonary hypertension are associated with reduced risk of age-related macular degeneration: a cohort study'.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42538387},
issn = {1476-5454},
}

@article {pmid42539849,
year = {2026},
author = {Malmin, A and Olsen, MVT and Thomseth, VM and Kjellevold Haugen, IB and Utheim, TP and Forsaa, VA},
title = {Long-term Impact of Intravitreal Injections on the ocular surface; a 2-year follow-up study.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1829818},
pmid = {42539849},
issn = {2674-0826},
abstract = {BACKGROUND: Intravitreal injection (IVI) therapy is the most frequently performed intraocular procedure worldwide, with topical povidone-iodine (PVP-I) as the standard pre-injection antiseptic. However, PVP-I has been shown to exert cytotoxic effects on the ocular surface. The purpose of this study was to evaluate the impact of two years of serial anti-vascular endothelial growth factor (VEGF) IVI on ocular surface parameters.

METHODS: Patients with neovascular age-related macular degeneration (nAMD) receiving unilateral intravitreal anti-VEGF injections were examined at two time points, separated by a two-year interval. An aseptic protocol with PVP-I was applied prior to each injection. Tear meniscus height (TMH), bulbar redness (BR), and meibomian gland (MG) loss were assessed using the Oculus Keratograph 5M, with the fellow eye serving as control. For statistical analysis, the related-samples Wilcoxon signed-rank test was applied to non-normally distributed data, and the paired-sample Student's t-test to normally distributed data.

RESULTS: Sixty patients (mean age, 78.6 ± 8.5 years; range, 55-96) were included. Between examinations, patients received a mean of 15.5 ± 6.5 IVI (range, 5-30). A significant increase in mean BR was observed in untreated fellow eyes compared with baseline measurements (1.68 ± 0.47 vs. 1.41 ± 0.46; p < 0.001). At follow-up, BR was significantly higher in fellow eyes than in treated eyes (p < 0.001), and this difference had increased over the study period. Median TMH increased significantly in untreated eyes (0.42 mm [IQR, 0.28-0.57] vs. 0.31 mm [IQR, 0.23-0.47]; p = 0.003), whereas the increase in treated eyes was not significant (p = 0.74). At follow-up, mean TMH did not differ significantly between treated and fellow eyes (p = 0.15). Both treated and untreated eyes showed significant MG loss after two years of serial IVI; however, no significant differences in mean MG loss were detected between eyes in either the upper or lower eyelid at follow-up.

CONCLUSIONS: Eyes receiving repeated intravitreal anti-VEGF injections with preoperative PVP-I antisepsis were significantly less hyperemic than fellow untreated eyes, and this difference increased over two years of continued treatment. Potential mechanisms include a beneficial alteration of the ocular surface microbiome by PVP-I or an antiangiogenic effect of anti-VEGF therapy.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04458012, identifier NCT04458012.},
}

@article {pmid42536333,
year = {2026},
author = {Hashiya, N and Maruko, I and Tanaka, K and Honjo, J and Miyara, Y and Watanabe, Y and Maruko, R and Nakai, A and Wakatsuki, Y and Itagaki, K and Maehira, M and Terao, N and Kataoka, K and Okada, AA and Koizumi, H and Mukai, R and Sekiryu, T and Mori, R and , },
title = {Six-month outcomes with a reduced two-injection induction (2+TAE) regimen of aflibercept 8 mg in treatment-naive neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42536333},
issn = {1613-2246},
abstract = {PURPOSE: To evaluate 6-month outcomes of aflibercept 8 mg administered with two monthly injections followed by a treat-and-extend (TAE) regimen in treatment-naïve neovascular age-related macular degeneration (nAMD).

STUDY DESIGN: Multicenter retrospective study.

METHODS: This study included 107 treatment-naïve eyes with nAMD, of which 91 eyes of 90 patients (mean age, 74.7 ± 9.4 years) followed for 6 months were analyzed. All eyes received two consecutive monthly injections of aflibercept 8 mg (induction), followed by TAE. Best-corrected visual acuity (BCVA, logMAR), optical coherence tomography (OCT)-based anatomical outcomes, and adverse events were assessed.

RESULTS: Sixteen eyes were excluded, mainly due to being lost-to-follow-up or having had treatment changed to an alternative drug. No serious adverse events were observed. Mean BCVA improved from 0.43 ± 0.36 at baseline to 0.37 ± 0.42 at 6 months (P = 0.032). Retinal thickness, pigment epithelial detachment height, and subfoveal choroidal thickness significantly improved (all P < 0.05). The mean number of injections over 6 months was 3.4 ± 0.5, and the mean treatment interval at the end of 6 months was 11.6 ± 2.2 weeks. A dry macula was achieved in 70.3% of eyes, with a higher rate in eyes achieving a dry macula after a two-injection induction than in those requiring a three-injection induction (80.0% vs 51.6%, P < 0.01).

CONCLUSIONS: Eyes achieving a dry macula after two injections had higher 6-month dry rates than those requiring a third injection. Early treatment response may help predict treatment burden and guide individualized management strategies.},
}

@article {pmid42536362,
year = {2026},
author = {Chujo, S and Baek, J and Uji, A and Quarta, A and Chung, YC and Kwak, H and Soylu, C and Abbasgholizadeh, R and Alhelaly, M and Rattu, R and Huang, J and Corradetti, G and Velaga, S and Nittala, MG and Sadda, SR},
title = {Quantitative Evaluation of Geographic Atrophy Progression Using Geographic Atrophy Lesion Front Displacement.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {8},
pages = {64},
doi = {10.1167/iovs.67.8.64},
pmid = {42536362},
issn = {1552-5783},
mesh = {*Geographic Atrophy/diagnosis ; Humans ; Disease Progression ; Retrospective Studies ; Fluorescein Angiography/methods ; Female ; Male ; Aged ; Follow-Up Studies ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: To evaluate the temporal behavior and relative variability of a margin-based metric, lesion front displacement, for quantifying geographic atrophy (GA) progression secondary to age-related macular degeneration and to compare its performance with conventional metrics.

METHODS: This retrospective longitudinal analysis included 103 untreated fellow eyes from the MAHALO clinical trial with GA and 18-month follow-up. Fundus autofluorescence images were obtained at baseline and 6, 12, and 18 months. Five progression metrics were calculated: total area change, square root area change, total perimeter change, perimeter-adjusted growth rate (λ'PA), and lesion front displacement. Linearity was assessed using simple linear regression and the Harvey-Collier test. Variability was evaluated using standard deviation, variance ratios, and the Fligner-Killeen test.

RESULTS: Linearity was rejected for area and square root area change but not for lesion front displacement, perimeter change, or λ'PA. Lesion front displacement showed a relatively higher coefficient of determination (R2 = 0.504), whereas area (0.116), square root area (0.104), perimeter (0.001), and λ'PA (0.018) exhibited lower goodness of fit to a linear model. Lesion front displacement demonstrated lower dispersion across follow-up intervals. Variance ratio analysis indicated greater variability for all comparator metrics. Variability was significantly lower for lesion front displacement than for perimeter change and λ'PA at 12 and 18 months (P < 0.05).

CONCLUSIONS: Lesion front displacement demonstrated more consistent linear approximation and lower variability compared with several conventional GA progression metrics. This margin-based approach may serve as a complementary metric for longitudinal assessment of GA progression.},
}

*Geographic Atrophy/diagnosis
Humans
Disease Progression
Retrospective Studies
Fluorescein Angiography/methods
Female
Male
Aged
Follow-Up Studies
Tomography, Optical Coherence/methods

@article {pmid42536670,
year = {2026},
author = {Cardaras, A and Kim, S and Yuan, Y and Livnat, I and Yanagihara, RT and Saul, R and De Oca, GM and Zheng, K and Browne, AW},
title = {A computer vision-based approach for automatically extracting data from bar chart raster images to facilitate meta-analysis of biomedical literature.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0347081},
pmid = {42536670},
issn = {1932-6203},
mesh = {Convolutional Neural Networks ; *Image Processing, Computer-Assisted/methods ; Humans ; Macular Degeneration ; Algorithms ; Publications ; },
abstract = {Although bar charts are widely used in scientific publications, their rasterized format within Portable Document Format (PDF) files complicates automated data extraction, hindering large-scale evidence synthesis and meta-analysis. To address this, we developed and evaluated an automated pipeline for extracting quantitative data from bar charts embedded in the biomedical literature. The four-stage pipeline comprises (1) image extraction and panel segmentation, (2) optical character recognition (OCR)-based text detection, (3) image disassembly to identify chart components, and (4) data reconstruction using numeric parsing and axis-based interpolation. The system combines edge detection, morphological operations, and convolutional neural network (CNN)-based figure classification using a transfer-learned Inception v3 model. Performance was validated on randomized controlled trials in age-related macular degeneration, with manually annotated values from a semi-automated labeling tool as the reference standard, and agreement was assessed using Bland-Altman analysis. Across 28 bar charts from ten publications, the pipeline correctly recognized 92.9% (95% confidence interval [CI], 77.4-98.0) of figure types, 96.0% (95% CI, 94.2-97.3) of text blocks, and 79.1% (95% CI, 74.7-83.0) of bars. For numerical reconstruction, 81.2% (95% CI, 76.3-85.2) of bar values fell within ±5% of the reference standard, 63.0% (95% CI, 57.3-68.3) within ±2%, and 48.6% (95% CI, 43.0-54.3) within ±1%. Bland-Altman analysis showed a small negative bias of -0.18 (95% CI, -0.34 to -0.02), with 94.9% of differences within the limits of agreement. Most outliers arose from OCR digit misclassification or ambiguous bar boundaries. This proof-of-concept study demonstrates the feasibility of automated data extraction from bar charts using a hybrid approach that combines image-processing heuristics with CNN-based classification. Although currently limited to bar charts and a single clinical domain, the pipeline represents a step toward scalable, end-to-end systems for automated evidence extraction to support meta-analyses across the biomedical literature.},
}

Convolutional Neural Networks
*Image Processing, Computer-Assisted/methods
Humans
Macular Degeneration
Algorithms
Publications

@article {pmid42527415,
year = {2026},
author = {Bhuiyan, A and Govindaiah, A and Otero-Marquez, O and Fabczak-Kubicka, A and Bhuiyan, T and Tai, K and Deobhakta, A and Smith, T},
title = {A prospective study for validating an automated AI-based system for detecting age-related macular degeneration in clinical settings.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42527415},
issn = {2045-2322},
support = {R44EY031202/NH/NIH HHS/United States ; },
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; Female ; Aged ; Male ; Prospective Studies ; *Artificial Intelligence ; Sensitivity and Specificity ; Middle Aged ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early detection is essential for implementing preventative measures that can slow or stop the progression of late AMD. This study evaluates the performance of an AI-based system designed to detect referable AMD, defined as more than early AMD (mteAMD), in adults over 50 who have not been previously diagnosed. Using color fundus photographs, we recruited 845 subjects from three primary care and three general ophthalmology clinics in New York City. Non-dilated images of both eyes were taken, and for validation, dilated images were reviewed by three ophthalmologists who classified the cases as no AMD, early, intermediate, or late AMD. The system's performance was assessed on both a per-patient and per-eye basis, comparing its results to expert gradings using metrics such as AUC, sensitivity, specificity, positive predictive value, and negative predictive value. For identifying mteAMD at the subject level, the AI system achieved an AUC of 0.92, with a sensitivity of 90.27% and specificity of 83.36%, demonstrating its strong potential for early diagnosis and screening of AMD in real-world clinical settings.},
}

Humans
*Macular Degeneration/diagnosis/diagnostic imaging
Female
Aged
Male
Prospective Studies
*Artificial Intelligence
Sensitivity and Specificity
Middle Aged
Aged, 80 and over

@article {pmid42528138,
year = {2026},
author = {Zeng, Y and Zhang, T and Cornish, E and Lee, SR and Yam, M and Eminhizer, M and Zeng, J and Zhang, J and Zeng, S and Arafah, ADB and Wei, X and Yang, J and Zhu, M and Chang, A and Zhang, M and Du, J and Zhu, L and Gillies, MC},
title = {Dysregulated Proline Metabolism Contributes to Retinal Fibrosis in Neovascular AMD: Therapeutic Potential of Prolyl-4-Hydroxylase Inhibition.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.07.044},
pmid = {42528138},
issn = {1525-0024},
abstract = {Subretinal fibrosis, a major cause of irreversible vision loss in neovascular age-related macular degeneration (nAMD), is driven by excessive deposition of extracellular matrix such as collagens. While proline metabolism is known to play a critical role in collagen biosynthesis and fibrosis, its involvement in subretinal fibrosis remains unclear. Here, we characterized the progression of fibrovascular lesions in JR5558 mice, observing significant molecular alterations as early as 4 weeks of age and phenotypic changes by 8 weeks. Transcriptomic and metabolomic analyses revealed elevated levels of 4-hydroxyproline, an essential component of collagen, alongside significant alterations of other fibrosis-related pathways. P4HA1, a catalytic subunit of prolyl-4-hydroxylase essential for 4-hydroxyproline biosynthesis, was prominently expressed in fibrotic lesions in retinas of JR5558, laser-induced murine models and human eyes with nAMD. Targeting P4HA1 with the small-molecule inhibitor diethyl pythiDC significantly attenuated fibrovascular lesion expansion in the JR5558 mouse model and reduced collagen turnover in human retinal pigment epithelium cells. Treatment responses in JR5558 mice were lesion-cluster dependent, with the combination of diethyl pythiDC with aflibercept showing selective antifibrotic benefit in moderate lesion cluster. These findings support a potential role of proline metabolism, particularly proline hydroxylation, in subretinal fibrosis. Inhibiting P4HA1 with diethyl pythiDC inhibited fibrosis in the models we studied, highlighting a potential therapeutic strategy.},
}

@article {pmid42528715,
year = {2026},
author = {Matsuki, T and Akiyama, K and Watanabe, K and Noda, T and Sasaki, M},
title = {Early retinal volume changes after switching to brolucizumab in refractory neovascular age-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1872499},
pmid = {42528715},
issn = {2674-0826},
abstract = {BACKGROUND: This retrospective observational study primarily focused on the evaluation of early anatomical changes and intraocular inflammation (IOI) following the switch to intravitreal injection of brolucizumab (IVBr) in patients with neovascular age-related macular degeneration (nAMD) who were refractory to aflibercept or ranibizumab and unable to extend injection interval beyond 10 weeks while resolving retinal fluids.

RESULTS: Data from 23 patients were analyzed. Switch to brolucizumab resulted in rapid decreases in central foveal retinal thickness (CRT) (247 (130) to 227 (94)) μm, P < 0.001), pigment epithelial detachment volume (0.18 (0.47) to 0.11 (0.19) mm³, P = 0.04) and central choroidal thickness (159 (118) to 168 (78) μm, P = 0.018), although decrease in central retinal volume (CRV) (9.80 (1.40) to 9.70 (1.30) mm³, P = 0.111) was not significant.Three eyes exhibited IOI, observed on post-injection day 2 after the second IVBr. Two eyes exhibited only mild anterior chamber inflammation, while one eye exhibited vasculitis obliterans. While CRT decreased, CRV increased in all three eyes.As a post-hoc analysis, CRV in eyes without IOI exhibited significant decrease (9.90 (1.45) to 9.70 (1.20) mm³, P = 0.002).

CONCLUSION: Switch to brolucizumab therapy resulted in early anatomical changes. An increase in CRV despite improvement in central foveal parameters may represent a potential warning sign of brolucizumab-associated IOI and warrants further prospective validation.},
}

@article {pmid42529820,
year = {2026},
author = {Kheirkhah, A and Oszvar-Kozma, M and Lamina, C and Stark, KJ and Afonyushkin, T and Zimmermann, ME and Brandl, C and Heid, IM and Kronenberg, F and Binder, CJ},
title = {Circulating IgM Antibody Levels Against Oxidation-Specific Epitopes and Their Association With Age-Related Macular Degeneration.},
journal = {Arteriosclerosis, thrombosis, and vascular biology},
volume = {},
number = {},
pages = {},
doi = {10.1161/ATVBAHA.126.324949},
pmid = {42529820},
issn = {1524-4636},
abstract = {BACKGROUND: Cardiovascular disease (CVD) is associated with age-related macular degeneration (AMD), suggesting shared pathogenic pathways. Natural IgM antibodies targeting oxidation-specific epitopes (OSEs) are well characterized in CVD and may contribute to AMD. To date, no observational study has assessed the association between OSE-IgM and AMD, including among individuals with concomitant CVD. Here, we investigate this relationship in large population-based cross-sectional data of old-aged individuals.

METHODS: We measured IgM antibodies against phosphocholine-modified BSA (PC), MDA-LDL (malondialdehyde-modified low-density lipoprotein), and CuOx-LDL (copper-oxidized LDL) in up to 2264 participants with and without AMD of the AugUR study (Age-Related Diseases: Understanding Genetic and Nongenetic Influences-a Study at the University of Regensburg; 627 cases, 1637 controls; age, 70-95 years). Antibody levels were inverse-normalized, and multinomial mixed regression analyses were performed to evaluate their associations with different AMD stages.

RESULTS: Women exhibited significantly higher levels of all 3 OSE-IgM compared with men. Elevated levels of IgM against PC were associated with 12% decreased odds (odds ratio, 0.88 [95% CI, 0.80-0.97]; P=0.01) for any AMD. When we investigated OSE-IgM associations with different stages of AMD (early AMD, late AMD), we found that all 3 OSE-IgM were associated with ≈20% lower odds for late AMD, but none with early AMD. Associations of OSE-IgM with late AMD were stronger in men than in women. Of the participants, 490 individuals had documented CVD. A significant interaction was observed between levels of PC IgM and CVD status in their associations with early AMD (P=0.049). In a subset of participants with CVD, PC IgM levels were associated with 34% decreased odds (odds ratio, 0.66 [95% CI, 0.51-0.86]; P=0.002) for early AMD.

CONCLUSIONS: This study identifies an inverse association between IgM antibodies targeting PC, MDA-LDL, and CuOx-LDL and late AMD, but not with early AMD. However, in the early stage of AMD, an association with PC IgM is only observed when the participants had documented CVD. These findings may suggest a possible protective role of OSE-IgM antibodies in AMD pathogenesis and progression.},
}

@article {pmid42530462,
year = {2026},
author = {Baddar, D and Fouad, Y and Salem, NO and Feo, A and Nowara, M and Sarraf, D},
title = {Type 4 macular neovascularization in eyes with diabetic retinopathy.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004948},
pmid = {42530462},
issn = {1539-2864},
abstract = {PURPOSE: To report recently described type 4 macular neovascularization (T4MNV) in eyes with diabetic retinopathy (DR).

METHODS: A retrospective analysis including nine eyes with DR (and without any features of age related macular degeneration or AMD) that displayed T4MNV with optical coherence tomography (OCT) and OCT angiography (OCTA).

RESULTS: The mean age of the patients was 64 years, and the mean duration of diabetes mellitus was 20 years. All patients displayed unilateral T4MNV with an average visual acuity of 20/500 in the affected eye. Seven of the nine patients (77.8%) were diagnosed with proliferative DR, and the remaining exhibited severe non-proliferative DR. Central posterior hyaloid fibrosis was detected in 7/9 eyes (77.8%) and showed flow on OCTA in 4/9 eyes (44.4%). All 9 eyes showed subretinal hyperreflective material (SHRM) on OCT corresponding to Type 2 (and Type 1) MNV on OCT and OCTA. Drusen were not detected in any of the 9 affected or fellow eyes.

CONCLUSION: T4MNV can occur in eyes with long-standing DR without signs of AMD. It is possible that early identification of T2MNV and timely anti-VEGF intervention may potentially mitigate progression to T4MNV, but this requires validation with prospective analysis. Early recognition of T4MNV imaging features is important in counseling patients about the poor visual prognosis.},
}

@article {pmid42530765,
year = {2026},
author = {Wang, L and Guo, ZY and Hu, FX and Zhang, CY and Yuan, Y and Zhou, BQ and Peng, YT and Pang, L and Wang, Y},
title = {Correction: Next-generation sequencing reveals aqueous MicroRNA and piRNA signatures in age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
doi = {10.1007/s11010-026-05681-0},
pmid = {42530765},
issn = {1573-4919},
}

@article {pmid42530827,
year = {2026},
author = {Lee, J},
title = {Beyond Typical AMD: A Vodcast Exploring the Clinical and Therapeutic Landscape of PCV.},
journal = {Advances in therapy},
volume = {},
number = {},
pages = {},
pmid = {42530827},
issn = {1865-8652},
abstract = {Polypoidal choroidal vasculopathy (PCV) is a vascular disease of the choroid characterized by polypoidal lesions and a branching vascular network, leading to recurrent exudation and hemorrhage. It is a major cause of visual disability and is particularly prevalent in Asian populations. PCV is similar to neovascular age-related macular degeneration (nAMD) in morphological characteristics but is increasingly recognized as part of the pachychoroid disease spectrum, although consensus has yet to be reached. Despite overlapping features with nAMD, PCV demonstrates distinct pathophysiology and treatment response, necessitating accurate differentiation for management optimization. Diagnosis relies on multimodal imaging, with indocyanine green angiography (ICGA) as the gold standard, supported by optical coherence tomography (OCT) and OCT angiography. Anti-vascular endothelial growth factor (VEGF) therapy is the mainstay of treatment; however, responses are heterogeneous and are often suboptimal or incomplete. Long-term outcomes are frequently influenced by complications such as hemorrhage, fibrosis, and atrophy, highlighting the need for durable disease control. Advances in imaging and a better understanding of pachychoroid biology are enabling more personalized, activity-guided treatment strategies, with the potential to improve long-term outcomes and reduce treatment burden. In this vodcast, Professor Junyeop Lee discusses the key clinical and pathological features of PCV, how it differs from nAMD, and why it remains challenging to diagnose and manage. The discussion also explores evolving diagnostic approaches, current treatment strategies, and emerging directions in PCV care. Vodcast available for this article. Supplementary file1 (MP4 279147 KB).},
}

@article {pmid42533499,
year = {2026},
author = {Liu, Z and Li, H and Wang, C and Wang, T and Jiao, X},
title = {Beyond Glycemic Control: Metformin's Multi-Target Role in Preventing and Treating Major Ocular Pathologies.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683261474426},
doi = {10.1177/10807683261474426},
pmid = {42533499},
issn = {1557-7732},
abstract = {Metformin, a first-line therapy for type 2 diabetes, is increasingly recognized as a pleiotropic agent with potential relevance to ocular disease beyond glycemic control. Accumulating epidemiological evidence suggests that metformin exposure may be associated with reduced risk or slower progression of diabetic retinopathy, primary open-angle glaucoma, and age-related macular degeneration, while emerging data also implicate possible benefits in dry eye disease, uveitis, retinal vascular disorders, inherited retinal degeneration, and cataract. Mechanistically, metformin may modulate multiple disease-relevant pathways, including AMPK-mTOR signaling, autophagy, mitochondrial homeostasis, NRF2-mediated antioxidant defense, NF-κB/PARP-related inflammation, VEGF-driven angiogenesis, TXNIP-associated neurodegeneration, and TGF-β-dependent fibrosis. However, current evidence remains insufficient to support metformin as an established ophthalmic therapy. Most clinical data are observational and susceptible to confounding by diabetes severity, comorbidities, treatment indication, and survival bias; randomized evidence is limited, and the METforMIN trial did not significantly slow geographic atrophy progression. In addition, many preclinical studies use concentrations exceeding clinically achievable systemic exposure, whereas ocular pharmacokinetics, tissue bioavailability, transporter dependence, and dose-toxicity relationships remain poorly defined. Signals of dose-dependent risk, including high-intensity exposure in diabetic retinopathy and stress responses in meibomian gland epithelial cells, further underscore the need for caution. Future studies should prioritize prospective ocular endpoints, measured intraocular drug concentrations, target-engagement biomarkers, transporter-informed delivery strategies, and rigorous dose-ranging safety assessments.},
}

@article {pmid42534250,
year = {2026},
author = {Contreras-Salinas, H and Vázquez-Beltrán, JC and García-Sánchez, G and Quirarte-Justo, S and Gómez-Macías, SDC and Rodríguez-Herrera, LY},
title = {Disproportionality analysis of off-label intravitreal bevacizumab in the FDA Adverse Event Reporting System database.},
journal = {Therapeutic advances in drug safety},
volume = {17},
number = {},
pages = {20420986261462682},
pmid = {42534250},
issn = {2042-0986},
abstract = {BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor agent initially approved for cancer treatment, is widely used off-label in retinal vascular diseases; however, this use may carry safety risks, particularly when evidence from controlled clinical trials is limited. In this context, real-world evidence derived from large pharmacovigilance databases plays a critical role in evaluating its safety profile.

OBJECTIVES: Evaluate the safety profile of off-label intravitreal bevacizumab for the treatment of retinal vascular diseases using the FDA Adverse Event Reporting System (FAERS) database.

DESIGN: Disproportionality analysis using data mining of the FAERS database.

METHODS: Individual case safety reports (ICSRs) of intravitreal bevacizumab from Q1 2015 to Q2 2025 were extracted, and data mining methods (reporting odds ratio, proportional reporting ratio and Bayesian confidence propagation neural network) were applied to identify statistical disproportionality. In addition, a comparative risk analysis (odds ratio) was performed against ranibizumab.

RESULTS: Of the 1495 ICSRs (5232 adverse events (AEs)), 114 preferred terms were statistically significant in the disproportionality analyses; 52% were expected, 15% were related to lack of efficacy and 33% were unexpected. Furthermore, the comparative analysis suggests a higher risk of serious cardiovascular, ocular and systemic events with ranibizumab.

CONCLUSION: Most of the disproportionately reported AEs associated with bevacizumab were expected or related to product handling, underscoring the importance of using approved single-dose formulations. While this analysis suggests a lower risk of serious systemic AEs with bevacizumab than with ranibizumab, this finding should be interpreted with caution, as disproportionality analyses based on spontaneous reporting systems cannot confirm causal associations. Further evidence is needed to confirm the observed associations.},
}

@article {pmid42534283,
year = {2026},
author = {Ghorayeb, G and Ali, MH and Hadziahmetovic, M and Emerson, GG and Jumper, JM and Blim, JF and Lai, MM},
title = {OCT as a Dynamic Biomarker in Retinal Disease Management: Evidence, Decision Strategies, and Clinical Guidance for OCT Decision-Point Use.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261467124},
pmid = {42534283},
issn = {2474-1272},
abstract = {PURPOSE: To describe how optical coherence tomography (OCT) is used in retinal disease management to aid in decision-making, including whether to treat or observe, extend or shorten dosing intervals, switch therapy, and plan or assess surgical care.

METHODS: Pivotal randomized clinical trials and designs in neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and retinal vein occlusion (RVO) were reviewed to characterize how OCT is used within evidence-based retreatment and monitoring strategies, including newer faricimab and aflibercept 8 mg trial programs. These decision strategies were translated into scenario-based clinical guidance for real-world decision-point use.

RESULTS: Where randomized evidence is limited, particularly for selected surgical retina decision points, guidance reflects the authors' expert opinion as informed by available literature and common retina practice. OCT is used in trial protocols as an anatomic biomarker for nAMD, DME, and RVO to assess disease activity, treatment response and recurrence, and to determine individualized follow-up and retreatment intervals. OCT was often obtained at protocol visits during active therapy phases and at key reassessment points. When new symptoms, suspected recurrence, incomplete response, diagnostic uncertainty, or high-risk features are present, shorter assessment intervals may be appropriate.

CONCLUSIONS: OCT-guided, decision-linked monitoring is supported by contemporary randomized clinical trials as integral to the management of nAMD, DME, and RVO, while recognizing that OCT frequency is generally not randomized as an isolated variable. The risk of avoidable vision loss can be reduced with scenario-based retina clinical guidance that emphasizes OCT at clinical decision points, improving patient safety and enhancing individualized care.},
}

@article {pmid42534291,
year = {2026},
author = {Bhavsar, AP and Boucher, N and Fernando, R and Ishii, F and Sambhara, D},
title = {Examining Real-World Attrition Among Patients Undergoing Complement Inhibitor Intravitreal Therapy for Geographic Atrophy.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261467244},
pmid = {42534291},
issn = {2474-1272},
abstract = {PURPOSE: To identify characteristics of patients with geographic atrophy (GA) who received pegcetacoplan or avacincaptad pegol and discontinued treatment.

METHODS: Two complementary retrospective cohort studies of a large, geographically and demographically diverse, deidentified database were performed. One analysis assessed baseline characteristics. Eyes with 12 months of data were included in a subsequent analysis of follow-up changes/characteristics. Univariate and multivariate mixed-effects Cox proportional hazard and logistic regression models, respectively, were used to estimate the hazard ratio (HR) and odds ratio (OR) of attrition.

RESULTS: A total of 21 914 eyes were identified for the baseline analysis, 14 690 (67%) of which received pegcetacoplan and 7224 (33%) avacincaptad pegol. Mean (±SD) patient age was 82.1 ± 7.85 years. Treatment retention declined between 0 and 12 months. Baseline predictors of attrition were age older than 90 years (HR, 1.26; 95% CI, 1.03-1.55; P = .028), pegcetacoplan treatment (HR, 3.32; 95% CI, 2.92-3.76; P < .001), treated (HR, 1.56; 95% CI, 1.40-1.75; P < .001) and untreated (HR, 1.41; 95% CI, 1.21-1.64; P < .001) neovascular age-related macular degeneration (nAMD), visual acuity of less than 35 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (HR, 1.45; 95% CI, 1.25-1.67; P < .001), and subfoveal GA (HR, 1.15; 95% CI, 1.04-1.27; P = .007). Poor baseline visual acuity remained significant in the adjusted 12-month analysis. Significant predictors included new nAMD (OR, 3.02; 95% CI, 2.35-3.89; P < .001) and a loss of more than 5 ETDRS letters (OR, 1.36; 95% CI, 1.17-1.58; P < .001). nAMD treatment intervals of more than 6 weeks (OR, 0.59; 95% CI, 0.39-0.90; P = .014) and GA treatment intervals of 6 to 8 weeks (OR, 0.56; 95% CI, 0.43-0.74; P < .001) contributed to decreased odds of attrition.

CONCLUSIONS: Poor baseline vision and development of new nAMD are associated with patient attrition, and the combination of nAMD and GA and treatment burden challenges patient retention.},
}

@article {pmid42534447,
year = {2026},
author = {Zhang, X and Liu, H},
title = {SPI1 Promotes TNF-α-Induced Epithelial-Mesenchymal Transition-Like Changes in Retinal Pigment Epithelial Cells: Implications for the Pathogenesis of Age-Related Macular Degeneration.},
journal = {Journal of ophthalmology},
volume = {2026},
number = {},
pages = {8106992},
pmid = {42534447},
issn = {2090-004X},
abstract = {BACKGROUND/AIMS: Age-related macular degeneration (AMD) is a progressive degenerative disease of the retinal macula associated with aging, which is one of the main causes of vision loss in the elderly. This research aims to investigate the mechanism of SPI1 in EMT of RPE cells in AMD, providing new targets for AMD treatment.

METHODS: SPI1, ALKBH5, and NURR1 expression was assayed by RT-qPCR and Western blot in AMD patients and cell models. The relationship between SPI1 expression and clinical features of AMD patients was analyzed, and the correlations among SPI1, ALKBH5, and NURR1 were analyzed. The diagnostic value of SPI1 in AMD was verified via ROC curve. ROS levels were detected. N-cadherin and E-cadherin were detected by Western blot. Cell migration was detected by transwell assay. The binding of SPI1 to ALKBH5 in cells was verified. m6A levels on NURR1 were detected.

RESULTS: SPI1 and ALKBH5 were highly expressed, while NURR1 was lowly expressed in TNF-α-induced human RPE cells. SPI1 expression was correlated with age and staging of AMD patients. SPI1 expression exhibited a positive association with ALKBH5 expression, while showing a negative association with NURR1 expression. After downregulation of SPI1, N-cadherin was downregulated, E-cadherin was upregulated, ROS levels were decreased, and cell migration was reduced. SPI1 promoted ALKBH5 expression, and ALKBH5 downregulated NURR1 expression via m6A modification. ALKBH5 overexpression or NURR1 downregulation partially reversed the attenuating effect of SPI1 downregulation on EMT-like changes in RPE cells.

CONCLUSION: SPI1 stimulates EMT-like changes of RPE cells via the ALKBH5/NURR1 axis. This pathway may participate in AMD-related pathological processes.},
}

@article {pmid42534834,
year = {2026},
author = {Zhu, M and Yu, W},
title = {The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.},
journal = {Frontiers in aging neuroscience},
volume = {18},
number = {},
pages = {1817987},
pmid = {42534834},
issn = {1663-4365},
abstract = {Age-related macular degeneration (AMD) is a fundus oculi disease that progressively impairs the central vision of patients. To date, its pathogenesis has not been fully elucidated, and therapeutic options for dry AMD remain limited. Recently, chronic low-grade inflammation has been recognized as an important pathogenic factor in various neurodegenerative diseases, including AMD. The NLRP3 inflammasome, a key component of the innate immune system, has emerged as a critical integrator of retinal stress signals. This review first delineates the molecular architecture and activation modalities of the NLRP3 inflammasome, encompassing canonical, noncanonical, and alternative pathways, as well as its downstream cell death programs, with a particular focus on pyroptosis and PANoptosis. We describe how AMD-associated danger signals converge on NLRP3 inflammasome activation within distinct retinal cell populations and discuss how cell-type-specific NLRP3 responses differently shape retinal homeostasis, degeneration, and neovascularization. We further summarize current evidence indicating that the pathological consequences of NLRP3 activation vary across AMD progression, from amplification of chronic inflammation in early and intermediate AMD to promotion of retinal atrophy in geographic atrophy and angiogenic signaling in neovascular AMD. Finally, we evaluate emerging therapeutic strategies targeting the NLRP3 pathway and discuss the major translational challenges related to cell-type and disease-stage specificity, retinal delivery, and long-term safety. By integrating retinal triggers, cellular responses, senescence-associated inflammation, inflammatory cell death, disease phenotypes, and therapeutic opportunities into a unified framework, this review provides a comprehensive perspective on the role of NLRP3 inflammasome signaling in AMD pathogenesis and treatment.},
}

@article {pmid42521465,
year = {2026},
author = {Guo, X and Chen, Y and Xiong, R and Zhuo, S and Li, H and Zhu, Z and Zhu, Z and Zhang, L and Huang, W and Congdon, N and Wang, W},
title = {Persistence of severe global sex-based inequalities in the burden of visual impairment.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328771},
pmid = {42521465},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: Sex-based disparities in vision impairment are a major global health concern. This study quantifies these disparities across major blinding diseases and assesses their association with national-level gender inequality.

METHODS: In this repeated ecological analysis of Global Burden of Disease (GBD) 2023 data, we analysed sex-disaggregated age-standardised years lived with disability (YLD) rates and prevalence for major blinding diseases. Temporal trends were assessed using average annual per cent change (AAPC). Linear regression examined associations between sex differences and the Gender Development Index (GDI) and Gender Inequality Index (GII). Projections were performed using a Bayesian age-period-cohort model.

RESULTS: From 1990 to 2023, sex disparities persisted, with a higher AAPC in females than males (0.08% vs -0.06%). In 2023, females had higher YLD rates than males for blindness and vision loss (BVI) (300.9 vs 262.8 per 100 000; +14.5%), cataract (95.1 vs 75.0; +26.7%) and age-related macular degeneration (6.9 vs 5.8; +18.0%), while glaucoma was higher in males. The largest female excess for BVI was in South Asia (difference 69.9 per 100 000). Higher GII and lower GDI were significantly associated with larger sex disparities (β=34.3 per unit GII increase; β=-197.0 per unit GDI increase, all p<0.001). Without targeted intervention, disparities are projected to persist or widen by 2040.

CONCLUSION: Global sex disparities in vision impairment remained substantial from 1990 to 2023 and are projected to continue. The strong association with GDI and GII indicates these disparities are modifiable and linked to structural factors. Gender-sensitive policies are needed to achieve equity in eye health.},
}

@article {pmid42522009,
year = {2026},
author = {Tarhan, M and Jungk, NL and Brockmann, T and Meller, D and Hammer, M},
title = {Fluorescence lifetimes and choriocapillaris flow deficits in intermediate age-related macular degeneration: a cross-sectional study.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42522009},
issn = {1471-2415},
mesh = {Humans ; *Choroid/blood supply ; Female ; Cross-Sectional Studies ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Male ; *Regional Blood Flow/physiology ; Aged, 80 and over ; *Macular Degeneration/physiopathology/diagnosis ; Ophthalmoscopy/methods ; Aged ; Capillaries/physiopathology ; *Retinal Vessels/physiopathology ; },
abstract = {PURPOSE: To assess the association between retinal fluorescence lifetimes (τm) and choriocapillaris (CC) flow deficits (FD) in intermediate age-related macular degeneration (AMD).

METHODS: Twenty-six pseudophakic eyes with intermediate, non-exudative AMD (mean age 83 ± 5 years) underwent fluorescence lifetime imaging ophthalmoscopy (FLIO) and optical coherence tomography angiography (OCTA). Fluorescence lifetimes were recorded in short- and long-wavelength channels and analyzed across ETDRS subfields. CC flow deficits were quantified using local thresholding. Associations between τm and FD were evaluated using Spearman's rank correlation.

RESULTS: Mean τm values were consistently higher in the long-wavelength channel compared to the short-wavelength channel across all subfields. Mean CC FD increased from the outer ring (0.50 ± 0.07) to the central subfield (0.65 ± 0.11). Correlation coefficients between τm and FD ranged from - 0.07 to 0.37, with no statistically significant associations (all p > 0.05).

CONCLUSIONS: No statistically significant association was observed between fluorescence lifetimes and choriocapillaris flow deficits in this exploratory cohort. Although both biomarkers are known to be altered in AMD, the absence of evidence for a statistically significant spatial association suggests that FLIO and OCTA may reflect complementary aspects of disease pathology. Larger studies incorporating structural retinal biomarkers and longitudinal follow-up are warranted.

CLINICAL TRIAL REGISTRATION: Not applicable.},
}

Humans
*Choroid/blood supply
Female
Cross-Sectional Studies
Tomography, Optical Coherence/methods
Fluorescein Angiography/methods
Male
*Regional Blood Flow/physiology
Aged, 80 and over
*Macular Degeneration/physiopathology/diagnosis
Ophthalmoscopy/methods
Aged
Capillaries/physiopathology
*Retinal Vessels/physiopathology

@article {pmid42524100,
year = {2026},
author = {Liu, L and Cheng, L and Ren, Q and Chu, Z and Cheng, H},
title = {Selective reduction of the light peak-to-dark trough ratio in reticular macular disease: an electrooculography study.},
journal = {Frontiers in neuroscience},
volume = {20},
number = {},
pages = {1865041},
pmid = {42524100},
issn = {1662-4548},
abstract = {PURPOSE: To compare electrooculogram (EOG) parameters between eyes with reticular macular disease (RMD) and eyes with early-to-intermediate age-related macular degeneration (AMD) without reticular pseudodrusen (RPD), and to assess whether RMD is associated with generalized RPE-photoreceptor complex dysfunction.

METHODS: In this observational cross-sectional study, 42 eyes from 21 patients were analyzed (without-RPD group: 28 eyes; RMD group: 14 eyes). RMD was diagnosed using multimodal imaging (infrared reflectance and SD-OCT). EOGs were recorded with the RETI-port/scan 21 system according to ISCEV standards. Extracted parameters included dark trough (DT), light peak (LP), light rise time (Light Rise), and the LP:DT ratio. Group comparisons used the Wilcoxon rank-sum test. Linear regression evaluated the association between RMD and LP:DT ratio with and without adjustment for age.

RESULTS: Age did not differ between groups (median 69 vs. 72 years; P = 0.5). Absolute standing potentials were similar (DT: 598 vs. 681 μV, P = 0.2; LP: 1,092 vs. 1,150 μV, P = 0.8). Light rise time was also similar (8.00 [IQR 7.50-9.00] vs. 8.00 [IQR 7.00-9.00] min; P = 0.6). In contrast, the LP:DT ratio was significantly reduced in RMD (1.65 [1.50-1.80]) compared with without-RPD controls (1.90 [1.80-2.10]; P = 0.0043). RMD was independently associated with a lower LP:DT ratio (β = -0.25, 95% CI [-0.41 to -0.09]; P = 0.004).

CONCLUSION: Compared with AMD eyes without RPD, RMD eyes demonstrate a selectively reduced LP:DT ratio without a change in absolute standing potentials or light rise timing. This EOG pattern supports attenuated light response consistent with generalized dysfunction of the RPE-photoreceptor complex in RMD.},
}

@article {pmid42524714,
year = {2026},
author = {Birner, K and Frank-Publig, S and Mai, J and Eidenberger, A and Schrittwieser, J and Leitner-Barrios, G and Barasits, M and Gumpinger, M and Reiter, GS and Sacu, S and Schmidt-Erfurth, U},
title = {Systematic quantification of outer retinal morphology in three different SD-OCT devices in geographic atrophy.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70210},
pmid = {42524714},
issn = {1755-3768},
abstract = {PURPOSE: To define interdevice differences in quantitative outer retinal biomarkers across three spectral-domain (SD) optical coherence tomography (OCT) devices in geographic atrophy (GA).

METHODS: Patients with GA prospectively underwent imaging using Spectralis (Heidelberg Engineering), Cirrus (Zeiss) and Maestro (Topcon) OCT devices. Ellipsoid zone (EZ) and outer nuclear layer (ONL) thickness, as well as EZ and retinal pigment epithelium (RPE) loss, were automatically pre-segmented and manually corrected. Quantitative measurements were compared between OCT devices using anova or Friedman tests. Bland-Altman analysis determined mean differences and 95% limits of agreement (LoA).

RESULTS: A total of 7080 B-scans from 120 OCT volumes of 40 eyes were analysed. Mean patient age was 80 ± 7 years. Mean EZ thickness in the 6-mm macular cube was 34.8 ± 4.6, 33.4 ± 4.1 and 31.0 ± 4.8 μm for Spectralis, Cirrus and Maestro, respectively, while mean ONL thickness was 77.8 ± 9.2, 78.5 ± 9.4 and 75.8 ± 9.6 μm. Interdevice differences were significant for EZ and ONL-thickness (all p < 0.05). Mean EZ thickness bias ranged from 1.5 to 3.8 μm, with the widest LoA between Spectralis and Maestro. Mean ONL-thickness bias ranged from -0.7 to 2.7 μm, with the widest LoA between Cirrus and Maestro. EZ-loss and EZ/RPE-loss-area also differed significantly (both p < 0.01).

CONCLUSION: Visualization and quantification of atrophic features at the level of the photoreceptors, including EZ thickness, EZ loss and ONL thickness, are influenced by the implemented OCT machine. Consistency in the OCT device during patient monitoring allows for the highest precision and eliminates interdevice differences in quantitative outcome measures.},
}

@article {pmid42525587,
year = {2026},
author = {Abdin, AD and Bedros, L and Kahlert, J and Munteanu, C and Mirsalehi, M and Langenbucher, A and Suffo, S and Seitz, B},
title = {Influence of Structural OCT Biomarkers on Functional Outcomes in Eyes With Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1},
doi = {10.1159/oph/aeeag005},
pmid = {42525587},
issn = {1423-0267},
abstract = {Purpose To investigate the effect of structural optical coherence tomography (OCT) biomarkers on the functional outcome in eyes with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (VEGF) therapy. Patients and Methods This retrospective study included 305 eyes of 254 patients with primary onset nAMD followed for 2 years. At baseline, several OCT structural biomarkers were assessed. We evaluated the interaction between the presence of all these biomarkers and the best corrected visual acuity (BCVA) in logMAR and the number of intravitreal injections, (IVI) administered over 2 years of treatment. Results The BCVA was 0.44±0.24 before treatment and 0.53±0.20 after 24 months (p=0.10). BCVA in logMAR after 2 years was significantly positively correlated with baseline presence of intraretinal fluid (IRF) (p <0.001), vitreomacular traction/adhesion (VMT/A) (p=0.04), photoreceptor layer damage (PRD) (p <0.001), and prechoroidal clefts (P=0.02). A significant positive correlation was found between the number of IVIs administered over 2 years and the presence of IRF (p=0.02) and subretinal hyperreflective material (SHRM) (p=0.03) at baseline. Conclusions The baseline presence of IRF, VMT/A, PRD, and prechoroidal clefts may be limit recovery of BCVA after 2 years of treatment. In addition, the presence of IRF and SHRM may be associated with a higher number of IVIs over 2 years of treatment.},
}

@article {pmid42526538,
year = {2026},
author = {Bantounou, MA and Emfietzoglou, M and Keenan, TDL and Baroutis, KG and Miller, JW and Vavvas, DG},
title = {Sustained High-Intensity Lipophilic Statin Use and Risk of Age-Related Macular Degeneration: A Target Trial Emulation.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.07.014},
pmid = {42526538},
issn = {2468-6530},
abstract = {OBJECTIVE: To evaluate whether sustained high-intensity lipophilic statin exposure is associated with reduced risk of incident nonexudative age-related macular degeneration (AMD) and progression from nonexudative to exudative AMD.

DESIGN: Target trial emulation retrospective cohort study.

PARTICIPANTS: Data were obtained from the Mass General Brigham database (2005-2025). For incident nonexudative AMD, hypertensive adults ≥55 years old were included if they were treated or untreated with high-intensity lipophilic statins (atorvastatin 40-80 mg or simvastatin 40-80 mg) within 2 years following the hypertension date. For progression to exudative AMD, adults ≥55 years old with hypertension and nonexudative AMD were included if they were treated or untreated within 1 year before the nonexudative AMD date.

METHODS: Sustained exposure was defined as ≥80% cumulative exposure during the exposure window. Exposed and unexposed individuals were propensity-score matched 1:1 on demographics, diabetes, obesity, healthcare utilization, calendar time. Subdistribution hazard ratios (sHR) accounting for the competing risk of death and inverse probability of censoring weighting (IPCW) hazard ratios (HR) were estimated for exposed vs. unexposed, adjusting for cardiovascular and chronic kidney disease. Sensitivity analyses included: positive-control (cataract), negative-control [posterior vitreous detachment (PVD)], any statin vs no exposure.

MAIN OUTCOME MEASURES: Incident clinically documented nonexudative AMD and progression to exudative AMD.

RESULTS: Over 2.8±1.8 years, 68/8,633 participants (0.79%) in the high-intensity lipophilic statin-exposed cohort and 88/8,633 (1.02%) in the unexposed cohort developed nonexudative AMD (sHR=0.53, 95%-CI, 0.38-0.74; P=0.0002; IPCW HR=0.53, 95%-CI, 0.37-0.76; P=0.0005). In the progression cohort, over 2.1±1.6 years, 66/1,082 high-intensity lipophilic statin-exposed participants (6.10%) and 85/1,082 unexposed participants (7.86%) progressed to exudative AMD (sHR=0.62, 95%-CI, 0.45-0.87; P=0.006; IPCW HR=0.61, 95%-CI, 0.43-0.87; P=0.006). Any statin use was not associated with AMD. For cataract, the sHR was 1.18 (95%-CI, 1.03-1.34; P=0.015), and the IPCW HR was 1.20 (95%-CI, 1.05-1.38; P=0.007). For PVD, the sHR was 1.00 (95%-CI, 0.81-1.22; P=0.96), and the IPCW HR was 1.00 (95%-CI, 0.81-1.24; P=0.99).

CONCLUSIONS: High-intensity lipophilic statin exposure was associated with lower clinically documented nonexudative AMD and progression to exudative AMD risk, whereas any statin exposure was not. These findings support regimen-specific statin effects on AMD risk. Confirmation in prospective studies and randomized trials with retinal outcomes is needed.},
}

@article {pmid42519412,
year = {2026},
author = {Chen, J and Tu, S and Zhu, Y and Li, Z and Chen, X and Shen, X and Deng, S and Zhuo, Y},
title = {Association between regular hypnotic use and age-related macular degeneration.},
journal = {Advances in ophthalmology practice and research},
volume = {6},
number = {3},
pages = {219-227},
pmid = {42519412},
issn = {2667-3762},
abstract = {BACKGROUND: Previous studies have confirmed the presence of benzodiazepine receptors in the retina, and exploratory research has suggested that the use of hypnotics may be linked to changes in retinal function and an increased risk of maculopathy. This indicates that regular use of hypnotic medications is likely associated with age-related macular degeneration (AMD). However, the precise relationship remains largely unclear. In this study, we aimed to investigate this association in the UK Biobank.

METHODS: Regular use of hypnotics, including benzodiazepines or Z-meds (non-benzodiazepine hypnotics such as zolpidem and zaleplon) were assessed at baseline. Nearest-neighbor propensity score matchings (PSM) were implemented to control for potential confounding variables. Cox proportional hazards regression with robust variance estimation was utilized to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for demographic, socioeconomic, systemic, and lifestyle variables. Sensitivity analyses were performed using traditional Cox proportional hazards regression on the original cohort, with additional subgroup analyses stratified by age group and sex.

RESULTS: Following the PSM procedure, 1899 benzodiazepine users and 7557 non-users were selected from the benzodiazepines cohort, and 321 Z-meds users and 1284 non-users were selected from the Z-meds cohort. A total of 262 participants in the benzodiazepines cohort developed incident AMD during follow-up after PSM, compared with 49 participants in the Z-meds cohort. Upon adjusting for covariates, the prolonged use of Z-meds was associated with an elevated AMD risk (HR: 2.15, 95% CI: 1.23-3.74, P=0.007), whereas no significant association was observed for the regular use of benzodiazepines (HR: 0.97, 95% CI: 0.73-1.30, P=0.854). Sensitivity analyses demonstrated consistent associations. Subgroup analyses also indicated consistent associations across various categories.

CONCLUSIONS: Prolonged use of Z-meds may elevate the risk of developing AMD. Given the increasing prescription of Z-meds for the treatment of insomnia, these findings underscore the necessity of considering potential ocular risks and requiring more frequent monitoring.},
}

@article {pmid42519923,
year = {2026},
author = {Gollamudi, S and Magdum, R and Bajpayee, P and Giri, N and Gupta, A and Lende, D},
title = {Clinical and Diagnostic Challenges of a Sporadic Adult-onset Vitelliform Macular Dystrophy.},
journal = {Annals of African medicine},
volume = {},
number = {},
pages = {},
doi = {10.4103/aam.aam_523_26},
pmid = {42519923},
issn = {0975-5764},
abstract = {Adult-onset vitelliform macular dystrophy (AVMD) is a relatively uncommon macular pattern dystrophy characterized by bilateral, symmetric, yellowish subretinal foveal lesions presenting in the fourth to sixth decades of life. It is frequently misdiagnosed as age-related macular degeneration or Best vitelliform macular dystrophy, making accurate diagnosis through multimodal imaging essential. We report a case of a 51-year-old male laundry worker who presented with bilateral gradual visual impairment and difficulty with near vision for 1 month. Best-corrected visual acuity was 6/6 in the right eye, whereas in the left eye, it was 6/36p-NI with appropriate correction. Anterior segment examination revealed bilateral posterior subcapsular cataracts and seborrheic blepharitis. Dilated fundus examination demonstrated multiple discrete yellowish subretinal deposits at the fovea in the right eye and a single, elevated, circular vitelliform lesion at the center of the macula in the left eye, with absent foveal reflex bilaterally. Fundus autofluorescence imaging confirmed focal hyperautofluorescence corresponding to the vitelliform deposits bilaterally. Structural optical coherence tomography (OCT) revealed dome-shaped subretinal hyperreflective material between the retinal pigment epithelium and photoreceptor layer in both eyes, consistent with Stage II vitelliform disease in the left eye and an earlier stage in the right eye. OCT angiography excluded choroidal neovascularization in both eyes. Karyotype report and Sanger sequencing show no chromosomal abnormality. A diagnosis of AVMD was established based on clinical and multimodal imaging findings. This case underscores the diagnostic value of multimodal imaging in establishing an accurate diagnosis of AVMD, a condition that carries a generally favorable prognosis when identified early and monitored appropriately. Clinician awareness of AVMD and its distinguishing imaging characteristics is critical to avoid misdiagnosis and ensure timely patient counseling and surveillance.},
}

@article {pmid42520050,
year = {2026},
author = {Öncül, H and Dağ, U and Alakuş, MF and Dertsiz Kozan, B and Savar Çağlayan, M},
title = {Association between ABO and Rh blood groups and subtypes of age-related macular degeneration: A cross-sectional study.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0354886},
pmid = {42520050},
issn = {1932-6203},
mesh = {Humans ; *ABO Blood-Group System ; Cross-Sectional Studies ; Female ; Male ; Aged ; *Macular Degeneration/blood ; *Rh-Hr Blood-Group System ; Risk Factors ; Middle Aged ; Odds Ratio ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment and is driven by complex genetic, inflammatory, and vascular mechanisms. ABO and Rh blood group antigens, which are expressed on vascular endothelium and involved in immune and hemostatic pathways, have been implicated in various systemic diseases; however, their potential association with AMD phenotypic variation remains unclear. In this cross-sectional study, 488 patients with clinically confirmed AMD from a tertiary referral center were included. AMD was classified as neovascular AMD (wet AMD) or nonneovascular AMD (dry AMD) based on multimodal imaging and standardized diagnostic criteria. ABO and Rh blood group data were obtained from medical records, and individuals with major known AMD risk factors, including smoking, alcohol consumption, and obesity, were excluded to reduce confounding. Associations between AMD subtypes and ABO blood groups and Rh factor were evaluated using the Pearson chi-square test, and crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The mean age of participants was 66.9 ± 4.7 years, and 273 patients (55.9%) had neovascular AMD. A statistically significant association was observed between ABO blood group distribution and AMD subtypes (χ[2] = 8.31, p = 0.040). A higher proportion of patients with neovascular AMD had blood group A, whereas blood group B was relatively more common among patients with nonneovascular AMD. However, individual pairwise crude odds ratio analyses did not demonstrate statistically significant associations for specific ABO blood groups. No association was observed for Rh status. These findings suggest a possible modest association between overall ABO blood group distribution and AMD phenotype; however, the clinical significance of this relationship remains uncertain, particularly in the absence of multivariable adjustment. Larger multicenter studies with comprehensive multivariable analyses are warranted.},
}

Humans
*ABO Blood-Group System
Cross-Sectional Studies
Female
Male
Aged
*Macular Degeneration/blood
*Rh-Hr Blood-Group System
Risk Factors
Middle Aged
Odds Ratio

@article {pmid42520059,
year = {2026},
author = {Lu, Z and Cao, H and Ma, C and Zheng, J and Ma, X},
title = {Mapping the Reliability-Readability Gap in the Education of Patients With Age-Related Macular Degeneration Across 6 Large Language Models: Comparative Evaluation Study.},
journal = {JMIR medical informatics},
volume = {14},
number = {},
pages = {e91016},
pmid = {42520059},
issn = {2291-9694},
mesh = {Large Language Models ; Humans ; *Macular Degeneration/therapy ; Reproducibility of Results ; *Patient Education as Topic/standards/methods ; *Comprehension ; },
abstract = {BACKGROUND: Artificial intelligence-generated health information is increasingly used by patients, but its reliability, visible transparency indicators, and readability remain uncertain in specialized ophthalmic conditions such as age-related macular degeneration (AMD).

OBJECTIVE: This study aimed to evaluate and compare the informational reliability, visible transparency indicators, overall quality, and readability of responses generated by 6 publicly accessible large language models (LLMs) to AMD-related patient-facing prompts under a zero-shot, single-turn prompting scenario.

METHODS: Thirty English-language AMD-related prompts were curated from Google Trends, the 2023 Chinese AMD guideline, and the 2025 American Academy of Ophthalmology Preferred Practice Pattern. Chinese guideline-derived prompts were translated and reviewed before model querying. Each finalized prompt was entered verbatim into ChatGPT-5.1-auto, DeepSeek-v3.2, Gemini-2.5-Flash-Thinking, Grok 4, Claude-Sonnet 4.5, and Qwen3-Max between October 10 and November 25, 2025. Two senior ophthalmologists (ZL and XM) blinded to model identity independently scored all responses using DISCERN, Ensuring Quality Information for Patients (EQIP), Global Quality Scale, and Journal of the American Medical Association benchmark criteria, with adjudication for disagreements. Readability was assessed using 6 standard formulas against a sixth-grade benchmark. Between-model differences were analyzed using Friedman tests with Holm-adjusted pairwise comparisons.

RESULTS: A total of 180 responses were analyzed. Interrater agreement was substantial to near-perfect across reliability instruments (κ=0.72-0.97). No model met the recommended sixth-grade readability target. Grok 4 achieved the highest scores on reliability-related instruments, including DISCERN (mean 46.40, SD 7.43) and EQIP (mean 74.33, SD 9.07), whereas DeepSeek-v3.2 generated the most readable responses, with the highest Flesch Reading Ease Score (mean 48.23, SD 9.16) and lowest Flesch-Kincaid Grade Level (mean 9.95, SD 1.87). Significant between-model differences were observed across all reliability and readability metrics (all P<.001).

CONCLUSIONS: Under zero-shot, single-turn prompting conditions, the evaluated public LLMs showed substantial model-dependent differences in AMD-related patient education quality and readability. No model met the sixth-grade readability benchmark, including those with comparatively stronger reliability performance. These findings support clinician oversight, readability optimization, and further evaluation before LLM-generated AMD information is used directly in patient-facing settings.},
}

Large Language Models
Humans
*Macular Degeneration/therapy
Reproducibility of Results
*Patient Education as Topic/standards/methods
*Comprehension

@article {pmid42521210,
year = {2026},
author = {Choi, S and Kim, J and Park, MS and Kwon, S and Cho, BJ},
title = {Real-World Treatment Outcome of Intravitreal Ranibizumab and Aflibercept in Pseudophakic Eyes with Neovascular Age-Related Macular Degeneration.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2026.0030},
pmid = {42521210},
issn = {2092-9382},
abstract = {PURPOSE: To evaluate the long-term real-world treatment outcome of intravitreal ranibizumab and aflibercept injections in pseudophakic eyes with neovascular age-related macular degeneration (nAMD), independently of the effect of cataract progression.

METHODS: Medical records of pseudophakic patients with nAMD who were treatment-naïve, underwent intravitreal injection of ranibizumab or aflibercept between March 2010 and August 2023, and then were followed up for at least 1 year were retrospectively reviewed. Demographic and clinical variables, including visual acuity (VA), central subfield thickness (CST), and total number of injections, were analyzed to assess the risk of poor treatment outcome.

RESULTS: A total of 93 treatment-naïve pseudophakic eyes from 93 patients were included, with 46 eyes receiving aflibercept injection. The mean VA improved from 51.0 letters at baseline to 57.4 letters at 3 months showing the greatest improvement, and then gradually declined to 53.0 letters, 52.9 letters, and 49.7 letters at 1, 2, and 5 years after the initiation of injections, respectively. In contrast, the mean CST significantly decreased from 351.2 ± 114.6 μm to 230.7 ± 93.5 μm at 3 months, followed by a mild increase to 271.8 ± 117.1 μm at 1 year, and remained stable at 271.4 ± 160.5 μm at 2 years. Thereafter, CST gradually decreased reaching 251.7 ± 125.2 μm by the fifth year. There were no statistically significant differences in VA or CST between the ranibizumab and aflibercept groups throughout the period. Factors associated with poor visual outcome defined as ≤ 35 letters at 3 years were solely limited to baseline VA.

CONCLUSIONS: For eyes with sustained long-term follow-up, the visual outcomes of pseudophakic patients with nAMD, unaffected by cataract progression, were maintained at a good level above baseline over 4 years after intravitreal injection in the real-world, while CST decreased consistently from 2 to 5 years after treatment.},
}

@article {pmid42427844,
year = {2026},
author = {Mohan, VB and Yucel, EI and Fine, I and Boynton, G},
title = {Using Virtual Patients to Predict Perceptual Outcomes for Optogenetic Sight Recovery Technologies.},
journal = {Research square},
volume = {},
number = {},
pages = {},
pmid = {42427844},
issn = {2693-5015},
abstract = {Optogenetics is emerging as a powerful approach for partial vision restoration, with at least three ongoing clinical trials in humans testing novel light-sensitive proteins (opsins) in patients with inherited retinal degenerative disorders. These therapies aim to restore light responsiveness by introducing opsins into surviving retinal cells, such as bipolar or ganglion cells, enabling them to generate neural activity in response to visual stimuli. One ongoing difficulty in selecting promising opsins for clinical development is that there is no way to predict patient perceptual outcomes from optogenetically evoked neural activity as measured ex vivo. Here, we introduce a virtual patient framework that quantitatively links the sensitivity and speed of opsin-mediated retinal responses to predicted patient outcomes, and show how this framework can predict temporal contrast sensitivity functions - a well-established measure of perceptual performance - from microbial opsin photocurrent responses. Our simulations demonstrate that opsin sensitivity and kinetics jointly determine perceptual outcomes, and that enhancing sensitivity at the expense of temporal resolution can degrade the perception of fast-moving stimuli. This computational platform provides a generalizable tool for comparing and selecting the most effective opsins for clinical translation, thereby guiding the design and optimization of next-generation sight restoration strategies.},
}

@article {pmid42504723,
year = {2026},
author = {XinYu, F and Yi, L and Liu, Z},
title = {Targeting of Nuclear Factor Erythroid 2-Related Factor 2 (NRF2) Signaling Pathway in Age-Related Eye Diseases: Molecular Mechanisms and Opportunities for therapy.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {8},
pages = {e70968},
pmid = {42504723},
issn = {1099-0461},
mesh = {Humans ; *NF-E2-Related Factor 2/metabolism ; *Signal Transduction/drug effects ; Animals ; *Eye Diseases/metabolism/therapy/drug therapy/pathology ; Oxidative Stress ; *Aging/metabolism/pathology ; Macular Degeneration/metabolism ; },
abstract = {Age-related eye diseases (AREDs), such as diabetic retinopathy (DR), cataract, glaucoma, age-related macular degeneration (AMD), presbyopia, and represent the primary sources of vision impairment globally. Numerous investigations have indicated that the onset and progression of these conditions are significantly linked to oxidative stress (OS) affecting the eye. The Keap1-Nrf2-ARE signaling pathway is a well-established mechanism that defends the body against OS and inflammation. This pathway is also implicated in the advancement of AREDs. However, the contribution of Nrf2 is likely to be disease-context dependent, and in multifactorial conditions such as glaucoma and dry eye disease, OS should be viewed as one interacting mechanism among several pathogenic processes rather than the sole or dominant driver. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) serves as a key modulator of numerous life processes, playing a critical role in antioxidant mechanisms, anti-inflammatory activities, antifibrotic responses, and cancer development. This review emphasizes the possible role of Nrf2 in the onset and progression of AREDs. Additionally, it explores various Nrf2 activators, encompassing noncoding RNAs and external substances, that regulate Nrf2 expression via distinct pathways within ocular disease models and eye cells, thereby safeguarding them from harmful alterations. However, most evidence supporting Nrf2-targeted interventions in age-related eye diseases remains preclinical, and important issues including disease-specific ocular delivery, target engagement in human tissues, long-term safety, and the potential risks of chronic Nrf2 activation must be addressed before clinical translation can be considered feasible. Consequently, Nrf2 may represent a significant target for the safeguarding of ocular cells against assorted stressors and the prevention of ocular ailments.},
}

Humans
*NF-E2-Related Factor 2/metabolism
*Signal Transduction/drug effects
Animals
*Eye Diseases/metabolism/therapy/drug therapy/pathology
Oxidative Stress
*Aging/metabolism/pathology
Macular Degeneration/metabolism

@article {pmid42506901,
year = {2026},
author = {Chen, J and Li, Y and Xiao, Y and Chen, D and Huang, W and Li, N and Liang, J and Zhan, J and Zhuo, Y and Leng, Y and Zhu, Y},
title = {Association between Pre-diagnostic Macular Thickness With Risk of Age-related Macular Degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004935},
pmid = {42506901},
issn = {1539-2864},
abstract = {PURPOSE: To determine whether specific pre-diagnostic macular thickness are associated with an increased risk of age-related macular degeneration (AMD).

METHODS: A total of 40,078 UK Biobank participants without baseline AMD who underwent optical coherence tomography (OCT) imaging were included. Macular thickness measurements were obtained via OCT across nine subfields of the Early Treatment Diabetic Retinopathy Study. Latent Profile Analysis (LPA) was employed to classify distinct pre-diagnostic macular thickness profiles, while cox proportional hazards models were utilized to estimate hazard ratios (HRs) between the identified profiles.

RESULTS: Two distinct pre-diagnostic macular thickness profiles were identified. Compared to profile 1 (n = 31,942), profile 2 (n = 8,136) was characterized by thinner inner and outer superior subfields, alongside thicker central and other outer subfields. Profile 2 was associated with significantly increased AMD risk compared to profile 1 (HR, 1.59; 95% confidence interval [CI], 1.32-1.90; P < 0.001). After adjustment for all covariates, the observed association persisted (HR, 1.39; 95% CI, 1.16-1.67; P < 0.001).

CONCLUSION: Distinct pre-diagnostic macular thickness patterns are associated with elevated AMD risk. These findings provide novel insights into potential early macular structural changes prior to AMD diagnosis, and may serve as novel biomarkers for early identification of AMD.},
}

@article {pmid42506910,
year = {2026},
author = {Bacherini, D and Kawamoto, K and Virgili, G and Rizzo, C and Baumal, CR and Chakravarthy, U and Curcio, CA and Faes, L and Freund, KB and Huang, D and Munk, MR and Pircher, M and Querques, G and Souied, E and Waheed, NK and Schwartz, R},
title = {Do OCTA morphological patterns in neovascular AMD actually matter? A scoping review of clinical utility and terminological overlap.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004936},
pmid = {42506910},
issn = {1539-2864},
abstract = {PURPOSE: Optical coherence tomography angiography (OCTA) has enabled detailed in vivo imaging of macular neovascularization (MNV) in neovascular age-related macular degeneration (nAMD), leading to a proliferation of morphological descriptive terms. This scoping review aimed to systematically map the existing literature on OCTA-based MNV morphology and evaluate its correlation with disease activity.

METHODS: A systematic literature search covering publications through 2025 was performed. After screening 2,445 titles and obtaining 60 full texts, 43 studies were included. Data on morphological terminology, study design, and correlation with disease activity were extracted and synthesized.

RESULTS: The included studies, encompassing a total of 2,712 eyes, identified a vast and heterogeneous lexicon of qualitative descriptors, including terms such as "medusa," "sea-fan," and "glomerulus", characterized by significant terminological overlap and inconsistent definitions across studies. Inconsistent, low-certainty associations between specific OCTA morphologies and MNV activity were identified across studies, with findings limited by significant methodological heterogeneity. The evidence for these patterns as reliable biomarkers of disease activity is weak and often contradictory, and several studies were found to use OCTA features to define activity, creating circular arguments that undermine their conclusions.

CONCLUSION: The current terminology for OCTA morphology in nAMD is fragmented and inconsistently applied. The link between these patterns and disease activity is poorly established, severely limiting their clinical utility. These findings highlight a need for a standardized, consensus-based framework for describing and interpreting OCTA findings in nAMD.},
}

@article {pmid42506959,
year = {2026},
author = {Satake, K and Koshiba, S and Haniuda, H and Amano, T and Hiura, M and Ishii, T and Horita, S},
title = {Preclinical Ocular Pharmacokinetics and Efficacy of Novel Tivozanib Eye Drops for Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {8},
pages = {55},
doi = {10.1167/iovs.67.8.55},
pmid = {42506959},
issn = {1552-5783},
mesh = {Animals ; Rabbits ; *Quinolines/pharmacokinetics/administration & dosage ; Ophthalmic Solutions ; Disease Models, Animal ; *Angiogenesis Inhibitors/pharmacokinetics/administration & dosage ; *Choroidal Neovascularization/drug therapy/metabolism ; *Phenylurea Compounds/pharmacokinetics/administration & dosage ; *Macular Degeneration/drug therapy/metabolism ; Choroid/metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Male ; Retina/metabolism ; Tissue Distribution ; Macaca fascicularis ; },
abstract = {PURPOSE: In neovascular age-related macular degeneration (nAMD), invasive intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is the current standard of care, highlighting the need for noninvasive eye drop formulations. We aimed to assess the ocular pharmacokinetics and anti-angiogenic efficacy of nanocrystallized tivozanib (nTivo) eye drops in rabbits and monkeys.

METHODS: We investigated the ocular distribution of nTivo eye drops and conventional microcrystallized tivozanib eye drops in albino and pigmented rabbits. The anti-angiogenic efficacy of nTivo eye drops was evaluated in laser-induced choroidal neovascularization (CNV) model monkeys.

RESULTS: In pigmented rabbits, nTivo eye drops showed up to 9.5-fold higher drug delivery efficiency to the retina/choroid relative to microcrystal formulations, indicating that nanocrystallization enhances the drug delivery efficiency of tivozanib to posterior eye tissues. Additionally, accumulation of the ocular exposure was observed with the repeated instillation of nTivo eye drops, and the elimination half-life (t1/2) of tivozanib was longer in the retina/choroid (247.5 hours) than in serum (49.7 hours). In comparison to albino rabbits, pigmented rabbits showed higher exposure (3.2-fold) and longer t1/2 (5.7-fold) in the retina/choroid, suggesting that the melanin binding properties of tivozanib potentially contribute to its accumulation and prolonged retention in the retina and choroid. In the monkey CNV model, nTivo eye drops significantly reduced the neovascularization lesion area.

CONCLUSIONS: The nTivo eye drop formulation may be a potential new treatment option for nAMD due to its preferable ocular pharmacokinetic and anti-angiogenic profiles based on potential contributions of nanocrystallization and the melanin binding properties of tivozanib.},
}

Animals
Rabbits
*Quinolines/pharmacokinetics/administration & dosage
Ophthalmic Solutions
Disease Models, Animal
*Angiogenesis Inhibitors/pharmacokinetics/administration & dosage
*Choroidal Neovascularization/drug therapy/metabolism
*Phenylurea Compounds/pharmacokinetics/administration & dosage
*Macular Degeneration/drug therapy/metabolism
Choroid/metabolism
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Male
Retina/metabolism
Tissue Distribution
Macaca fascicularis

@article {pmid42507292,
year = {2026},
author = {Fu, DJ and Riotto, E and Nicholson, L and Fasolo, S and Trivizki, O and Spooner, K and Sivaprasad, S and Faes, L},
title = {Real-World Outcomes of Faricimab for Polypoidal Choroidal Vasculopathy in a Multi-ethnic Cohort: A 12-Month Retrospective Study.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42507292},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aimed to evaluate 12-month real-world outcomes of faricimab for polypoidal choroidal vasculopathy (PCV) in a multi-ethnic cohort.

METHODS: This was a single-center retrospective cohort study of consecutive eyes with PCV diagnosed in routine care, treated with intravitreal faricimab, and with complete baseline and 12-month follow-up. One eye per patient was analyzed. Outcomes were reported for treatment-naïve and treatment-experienced eyes switched for persistent activity or limited durability. Primary endpoints were change in visual acuity (VA) and central subfield thickness (CST) at 12 months. Ethnicity-stratified outcomes were assessed secondarily.

RESULTS: The cohort comprised 159 eyes (40 treatment-naïve, 119 treatment-experienced). In treatment-naïve eyes, mean VA improved from 61 (standard deviation [SD] 14) letters at baseline by + 6.8 letters (SD 16; P < 0.01) at 12 months, with CST reduction of - 54 µm (SD 100; P < 0.01) and mean 9.6 (SD 4.2) injections. In treatment-experienced eyes, paired VA change at 12 months was minimal (+ 0.27 letters, SD 12; P > 0.05), while CST decreased significantly by - 40 µm (SD 110; P < 0.01). Eyes received a mean of 8.2 (SD 4.2) faricimab injections over 12 months. Exploratory ethnicity-stratified analyses demonstrated baseline heterogeneity across groups, with broadly favorable anatomical and functional outcomes observed across the multi-ethnic cohort, but subgroup sizes precluded comparative efficacy assessment.

CONCLUSIONS: In routine care, faricimab was associated with clinically meaningful visual improvement in treatment-naïve PCV and anatomical improvement in both treatment-naïve and -experienced eyes. Prospective studies with adequate ethnic representation are needed to validate these findings.},
}

@article {pmid42509296,
year = {2026},
author = {Kananen, F and Bode, H and Ollikainen, M and Immonen, I},
title = {Blood DNA methylation at AMD candidate loci in discordant monozygotic twins.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42509296},
issn = {2045-2322},
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment in older adults, with both genetic and environmental factors contributing to disease risk. Epigenetic mechanisms, particularly DNA methylation, may mediate the effects of environmental exposures on disease-relevant genes, yet their role in AMD remains poorly understood. To investigate blood DNA methylation differences associated with AMD severity, we studied 29 monozygotic twin pairs discordant for AMD from the Finnish Twin Cohort. This design controls for genetic background, sex, age, and shared early-life environment. Genome-wide DNA methylation was measured in whole blood using the Illumina HumanMethylation EPIC BeadChip. Analyses were restricted to 263 AMD candidate genes identified through prior genetic, epigenetic, and transcriptomic studies. Of 9,694 analyzed CpG sites, one site within ESYT1 reached statistical significance after multiple testing correction, but the corresponding methylation difference was below our predefined threshold for biological relevance. No CpG sites met both statistical and biological significance criteria. These findings do not provide evidence for large, systemic DNA methylation differences in peripheral blood at established AMD loci, though subtle effects below the detection limit of the current sample size cannot be excluded.},
}

@article {pmid42509399,
year = {2026},
author = {Lizzio, RAU and Mattioli, S and Nucci, P},
title = {Massive suprachoroidal haemorrhage in a patient with neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41433-026-04774-w},
pmid = {42509399},
issn = {1476-5454},
}

@article {pmid42510615,
year = {2026},
author = {Szulim, D and Kucharska, E and Machalińska, A and Kuprjanowicz, L and Czupryński, P and Szczuko, M},
title = {Effect of a Nutraceutical-Oriented Dietary Intervention on Serum Carotenoids and Antioxidant Vitamin Concentrations in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {7},
pages = {},
doi = {10.3390/antiox15070884},
pmid = {42510615},
issn = {2076-3921},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is one of the most common causes of irreversible impairment of central vision in the elderly population. Although anti-VEGF therapy remains the standard treatment for neovascular AMD, nutritional factors may influence disease progression and retinal health. The aim of this prospective controlled study was to evaluate the effects of an individualized dietary intervention with nutraceutical characteristics on serum concentrations of lutein, zeaxanthin, lycopene, vitamin A, and vitamin E in patients with neovascular AMD receiving anti-VEGF therapy.

METHODS: This prospective controlled study included 43 patients with neovascular AMD who completed a six-month follow-up period. Participants were allocated to either a control group receiving anti-VEGF therapy alone or an intervention group receiving anti-VEGF therapy combined with an individualized dietary plan. The dietary intervention emphasized foods naturally rich in carotenoids, antioxidant vitamins, trace elements, dietary fiber, and omega-3 fatty acids. Serum concentrations of lutein + zeaxanthin, lycopene, vitamin A, and vitamin E were determined using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) at baseline and after six months.

RESULTS: Serum lutein + zeaxanthin concentrations increased significantly within both groups (control 0.31 ± 0.61 to 0.49 ± 0.69 mg/L; intervention 0.51 ± 0.54 to 0.87 ± 0.89 mg/L). The increase was numerically larger in the intervention group, but the between-group difference was not statistically significant after adjustment for baseline concentrations (ANCOVA, p = 0.30). Lycopene increased significantly within the intervention group only (0.20 ± 0.15 to 0.43 ± 0.30 μmol/L); the between-group difference was not significant after baseline adjustment (p = 0.24). Vitamin A increased significantly within both groups and vitamin E within the intervention group only; however, no between-group difference remained significant after baseline adjustment (vitamin A p ≈ 1.00, vitamin E p = 0.96). The greatest increase in lutein + zeaxanthin concentrations was observed among participants with improved retinal status. These descriptive findings should be interpreted cautiously because subgroup analyses were not powered. Correlation analyses performed after six months demonstrated positive associations between serum lutein + zeaxanthin, lycopene, and vitamin A concentrations.

CONCLUSIONS: An individualized dietary intervention rich in naturally occurring bioactive compounds was associated with within-group improvements in serum carotenoid and antioxidant vitamin status. After adjustment for baseline values, between-group differences did not reach statistical significance, consistent with the exploratory, non-powered pilot design. These preliminary findings, including the observed effect sizes, are intended to inform the design of an adequately powered future study rather than to establish a between-group benefit of dietary management. Particularly pronounced changes were observed for lutein + zeaxanthin and lycopene concentrations. These findings support the potential role of dietary management as an adjunct to anti-VEGF therapy. However, given the nature of the study and the relatively small sample size, larger multicenter studies are needed to confirm these observations.},
}

@article {pmid42510910,
year = {2026},
author = {Kim, YR and Seol, A and Lee, SJ and Kim, JE and Song, HJ and Lim, SJ and Wang, SH and Ryu, YE and Choi, YW and Choi, SI and Hwang, DY},
title = {α-Iso-Cubebene Alleviates AMD-like Retinal Injury Through Modulation of Oxidative Stress and Inflammatory Response.},
journal = {Current issues in molecular biology},
volume = {48},
number = {7},
pages = {},
doi = {10.3390/cimb48070669},
pmid = {42510910},
issn = {1467-3045},
support = {F25YY8109033//National Research Foundation of Korea/ ; F26YY8109033//National Research Foundation of Korea/ ; },
abstract = {Although oxidative stress plays a critical role in age-related macular degeneration (AMD) progression, natural product-derived single compounds against AMD remain largely unexplored. We investigated the protective effects and underlying mechanism of α-iso-cubebene against AMD-like retinal injury. Alterations in key phenotypes for AMD were analyzed in AMD-mimicking models using ARPE-19 cells co-treated with blue light (BL) and N-retinylidene-N-retinylethanolamine (A2E), as well as BL-exposed BALB/c mice. In BL+A2E-treated ARPE-19 cells, α-iso-cubebene reduced intracellular reactive oxygen species (ROS) and nitric oxide (NO) production and restored superoxide dismutase (SOD) activity and nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting enhancement of the antioxidant defense system. Furthermore, α-iso-cubebene improved cell viability, reduced apoptotic cell populations, and regulated apoptosis-related signaling pathways under oxidative stress conditions. It also attenuated cyclooxygenase-2 (COX-2)-mediated inducible nitric oxide synthase (iNOS) signaling and was associated with reduced inflammasome-related signaling. Importantly, these protective effects were consistently observed regarding the protection of histopathological structure and normalization of inflammatory cytokines in the retina of BL-exposed BALB/c mice. Collectively, our results demonstrate that α-iso-cubebene, as a potential therapeutic candidate, alleviates AMD-like retinal injury and was associated with enhanced antioxidant responses and reduced inflammatory and apoptotic signaling markers.},
}

@article {pmid42511632,
year = {2026},
author = {Abdouh, M and Goyeneche, A and Yurchuk, M and Burnier, MN},
title = {Induction of Oxidative Stress on Retinal Pigment Epithelial Cells Triggered a Proangiogenic Environment.},
journal = {International journal of molecular sciences},
volume = {27},
number = {14},
pages = {},
pmid = {42511632},
issn = {1422-0067},
abstract = {Dry age-related macular degeneration (AMD) can progress to wet AMD when leaking capillaries grow under the macula. Although rare, this transition holds significant risk as it causes more rapid and severe vision loss. Oxidative stress is damaging to cellular components and plays a pivotal role in chronic diseases. We aim to determine whether oxidative stress in retinal pigment epithelial (RPE) cells elicits a proangiogenic microenvironment. We exposed human primary RPE cells to hydrogen peroxide (H2O2), and we analyzed their metabolic activity, and the production of reactive oxygen species (ROS) and angiogenic factors. In addition, we evaluated the potential of RPE cell-conditioned medium (CM) to induce HUVEC cell tube formation. RPE cells exposed to H2O2 displayed a dose-dependent decrease in their metabolic activity, and increased ROS levels. The analysis of the CM of exposed RPE cells revealed differential expression of a panel of proangiogenic factors. Notably, the expression of the major angiogenic factors (VEGF, FGF) was increased. Exposure of HUVEC cells to the CM of H2O2-exposed RPE cells promoted tube formation suggestive of microvessel formation. Our findings bring new insights into the role of oxidative stress in altering RPE cell behavior that might have consequences in the progression of AMD towards the exudative form.},
}

@article {pmid42512063,
year = {2026},
author = {Ikeuchi, E and Miki, A and Oka, T and Kishimoto-Kishi, M and Nakamura, M},
title = {Baseline Biomarkers Associated with Early Anatomical Response After Faricimab Loading Therapy in Treatment-Naïve Neovascular Age-Related Macular Degeneration.},
journal = {Biomedicines},
volume = {14},
number = {7},
pages = {},
doi = {10.3390/biomedicines14071590},
pmid = {42512063},
issn = {2227-9059},
abstract = {Background/Objectives: We identified baseline factors associated with early anatomical response to faricimab. Methods: This single-center retrospective study included 78 treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) receiving three monthly faricimab injections. Eyes with complete resolution of intraretinal and subretinal fluid on optical coherence tomography (OCT) at 16 weeks constituted the fluid-free group, and the remaining eyes were assigned to the persistent-fluid group. Baseline OCT features (including subretinal hyperreflective material [SHRM], pigment epithelial detachment [PED] subtypes, and central retinal and choroidal thickness) and clinical characteristics were compared, and ARMS2 (rs10490924) and CFH (rs800292) were genotyped as an exploratory analysis. Multivariable logistic regression identified associated factors. Results: Fifty-five eyes (70.5%) achieved complete fluid resolution. In multivariable analysis, SHRM was independently associated with a favorable early anatomical response, and fibrovascular PED with incomplete early fluid resolution (p = 0.019 and p = 0.026); in an exploratory model, the ARMS2 risk allele was associated with incomplete fluid resolution (p = 0.008), whereas CFH was not. Conclusions: In treatment-naïve nAMD, baseline SHRM was associated with a favorable early anatomical response to faricimab, whereas fibrovascular PED and a higher ARMS2 T-allele count were associated with incomplete early fluid resolution. These characteristic OCT and genetic features may help identify eyes at risk of an incomplete early response.},
}