@article {pmid41655333,
year = {2026},
author = {Guo, R and Huang, Y and Zhang, X and Qin, M and Sun, H and Jin, X and Xu, J and Kang, Y and Li, K and Zhou, Y and Nan, K and Zheng, Y and Liu, S},
title = {Long-term suppression of retinal degeneration with anti-VEGF agents-loaded hollow mesoporous silica nanoparticles.},
journal = {Colloids and surfaces. B, Biointerfaces},
volume = {262},
number = {},
pages = {115527},
doi = {10.1016/j.colsurfb.2026.115527},
pmid = {41655333},
issn = {1873-4367},
abstract = {Age-related macular degeneration (AMD) that leads to degeneration of the overlying photoreceptor in the macula and consequent loss of central vision is the leading cause of irreversible blindness in elderly population. Since vascular endothelial growth factor (VEGF) is pivotal for stimulating neovascularization, monthly intravitreal (IVT) injections of anti-VEGF agents have been used for eliminating neovascularization. However, repeated monthly IVT injections could cause side effects and serious complications. Herein, we report the development of two kinds of anti-VEGF agents (Ranibizumab (Ran) and Aflibercept (Afl))-loaded hollow mesoporous silica nanoparticles for effective treatment of AMD. The designed nanoparticles show no toxicity for both in vitro and in vivo, and could significantly inhibit VEGF-induced proliferation and cell migration. Long-term in vivo experiments in the laser photocoagulation induced choroidal neovascularization (CNV) model for wet AMD show that these nanoparticles effectively inhibit VEGF-induced neovascularization leakage and formation at least 8 weeks upon one IVT injection and therefore are a promising treatment strategy for AMD.},
}

@article {pmid41655020,
year = {2026},
author = {Gardner, A and Wang, S and Daniels, A and Li, D and Wu, C and Lin, L and Hong, C and Zhao, SR and Kruczek, K and Weist, G and Real, LB and Wicks, J and Nayal, M and Carter, A and Ott, C and Haurigot, V and Born, RT and Cepko, CL},
title = {AAV NRF2 Gene Therapy Preserves Retinal Structure and Function in Rodent Models of Oxidative Damage.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.02.005},
pmid = {41655020},
issn = {1525-0024},
abstract = {Dry age-related macular degeneration is the most frequent cause of visual impairment in individuals over age 50 in developed countries. It is characterized by deposits of oxidized proteins and lipids and results in progressive loss of high acuity vision. One major risk factor is smoking, which causes oxidative stress in many tissues, including the eye. We previously showed that an adeno-associated viral vector expressing human NRF2 (AAV8/Best1-NRF2), a transcription factor that regulates responses to oxidative damage, slowed degeneration in mouse models of another blinding disorder, retinitis pigmentosa, which also includes oxidative stress. Here, our AAV8/Best1-NRF2 vector was tested in a model of oxidative stress wherein sodium iodate was injected systemically, as this is often used to model dry age-related macular degeneration. Sodium iodate causes acute oxidative damage to the retinal pigment epithelial cells, which provide support to the photoreceptor cells. In addition, this toxin ultimately leads to photoreceptor death. Subretinal injection of AAV8/Best1-NRF2 led to protection of the retinal pigment epithelium and photoreceptors, as well as preservation of visual function, in rat and mouse sodium iodate models. AAV8/Best1-NRF2 may serve as an effective gene-agnostic therapy for diseases with oxidative stress, including dry age-related macular degeneration.},
}

@article {pmid41654857,
year = {2026},
author = {Forte, P and Ferro Desideri, L and Nassisi, M and Milanesi, F and Feo, A and Bagnasco, I and Iglesia, SM and Forte, G and Scandella, D and Roccatagliata, F and Fontana, V and Eandi, CM and Iester, M and Jolly, JK and Zinkernagel, MS and Viola, F and Nicolò, M},
title = {Drusen-specific dark adaptation profiles in intermediate age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00783-1},
pmid = {41654857},
issn = {2056-9920},
}

@article {pmid41654128,
year = {2026},
author = {Zhao, J and Montenegro, D and Cheng, S and Kim, HJ and Sparrow, JR},
title = {More insights from Abca4[-/-] mouse models of recessive Stargardt disease.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111261},
doi = {10.1016/j.jbc.2026.111261},
pmid = {41654128},
issn = {1083-351X},
abstract = {Mutations in the ATP-binding cassette transporter ABCA4 are responsible for recessive Stargardt disease (STGD1) a juvenile form of macular degeneration. In preclinical and clinical studies it has been shown that deficiency in ABCA4 leads to accelerated formation of the toxic bisretinoid fluorophores that form as the product of nonenzymatic reactions of retinaldehyde with phosphatidylethanolamine (PE) (2:1 ratio). Here, by comparing photoreceptor cell viability in albino versus agouti Abca4[-/-] mice and by dark-rearing albino Abca4[-/-] mice we show that photoreceptor cell degeneration in the Abca4[-/-] mouse is at least partially driven by light. Elevated vitamin A in chow and a high fat diet reduced photoreceptor cell viability. PE and N-retinylidiene-phosphatidylethanolamine were reduced as were steady state levels of retinoid in light-adapted eyes. As expected, bisretinoids, measured as short-wavelength fundus autofluorescence, were elevated in both pigmented and albino Abca4[-/-] mice. Hyperautofluorescent puncta in fundus autofluorescence images colocalized in spectral domain optical coherence tomography scans with aberrant hyperreflectivity that occupied photoreceptor-attributable bands and extended anteriorly to interrupt the ellipsoid zone and external limiting membrane. In epifluorescence images of Abca4[-/-] retina, retinal pigment epithelium was autofluorescent due to bisretinoid accumulation. Occasionally AF lesions extended anteriorly from the RPE to a horizontal band exhibiting less pronounced autofluorescence at the level of photoreceptor inner and outer segments. These lesions did not co-localize with IBA1-labeled microglia. The hyperautofluorescent foci that presented as hyperreflective lesions in SD-OCT form in photoreceptor inner segments and are reminiscent of fundus flecks in STGD1.},
}

@article {pmid41653377,
year = {2026},
author = {Manders, EA and van Der Wel, V and Schlingemann, R and Hollak, CEM and de Visser, SJ},
title = {Repurposing biosimilars, rethinking costs: a framework for sustainable drug pricing for repurposed bevacizumab for intravitreal injections.},
journal = {The European journal of health economics : HEPAC : health economics in prevention and care},
volume = {},
number = {},
pages = {},
pmid = {41653377},
issn = {1618-7601},
abstract = {Bevacizumab, originally developed by Genentech under the brand name Avastin[®] as an anti-cancer drug, has gained widespread off-label use in ophthalmology due to its similar mechanism of action to other anti-VEGF treatments and its significantly lower cost compared to available on label alternatives for ophthalmological indications. While off-label bevacizumab has been standard in clinical practice for over a decade, recently, a repurposed formulation (brand name: Lytenava[®], Outlook Therapeutics Ltd), developed specifically for vascular retinal conditions, received marketing approval from the European Medicines Agency. This raises questions about what the price for a repurposed formulation should reasonably be, reflecting the efforts to obtain regulatory approval. This paper examines potential cost-based-plus pricing for such a repurposed formulation of bevacizumab using a novel pricing framework across four scenarios. By evaluating the pricing structure through an analysis of critical cost components, including, among others, research and development expenditures, manufacturing costs, and cost-of-capital, the study proposes a price range of €73 to €177 per injection. The explicit breakdown of these cost components provides valuable insights into the economic structure of repurposed biosimilars like bevacizumab, emphasizing how a cost-based-plus pricing model can support more transparent and informed negotiations between pharmaceutical companies and healthcare payers. Ultimately, this approach contributes to the development of pricing strategies that balance affordability for healthcare systems with sustainable returns for manufacturers while fostering the broader development of repurposed treatments. The findings of this paper aim to advance the dialogue on equitable pricing for repurposed therapies.},
}

@article {pmid41650530,
year = {2026},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Comparative effectiveness and safety landscape of anti-VEGF therapies for neovascular age-related macular degeneration: Insights from a systematic review and network meta-analysis.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {196},
number = {},
pages = {118881},
doi = {10.1016/j.biopha.2025.118881},
pmid = {41650530},
issn = {1950-6007},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible vision loss in older adults. Intravitreal anti-vascular endothelial growth factor (VEGF) agents-including Aflibercept, Ranibizumab, Bevacizumab, Brolucizumab, and Faricimab-are the mainstay of therapy. However, their comparative efficacy and safety remain uncertain. This study aimed to compare the visual and systemic outcomes of these agents to inform clinical decision-making.

METHODS: A systematic search of PubMed, Embase, Scopus, and Web of Science from inception to September 2025 identified randomized controlled trials (RCTs) and observational studies comparing at least two anti-VEGF agents in nAMD. Eligible studies reported outcomes of best-corrected visual acuity (BCVA) change, visual gain ≥ 15 letters, mortality, or arteriothrombotic events. Risk of bias was assessed using Cochrane Risk of Bias 2 (RoB 2) and Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. A frequentist network meta-analysis estimated mean differences (MD) and odds ratios (OR) with 95 % confidence interval (CI). The protocol was registered in PROSPERO (CRD42025631298).

RESULTS: Sixteen studies involving 6758 participants (follow-up 3-24 months) met the inclusion criteria. For BCVA improvement, Aflibercept had the highest surface under the cumulative ranking curve (SUCRA) ranking (0.80), although all agents showed similar mean differences that were not statistically significant: aflibercept (MD 0.80; 95 % CI -1.20-2.80), Ranibizumab (0.64; -1.87-3.15), Bevacizumab (0.60; -2.02-3.22), Faricimab (2.20; -0.69-5.09), and Brolucizumab (4.20; -5.97-14.36). The larger point estimate for Brolucizumab reflects imprecision rather than superior visual efficacy. Mortality was lowest with Aflibercept (risk ratio (RR) 0.76; 95% CI 0.41-1.55). For arteriothrombotic events, no statistically significant differences were observed between anti-VEGF agents. Comparisons between Aflibercept and Bevacizumab (RR 1.11; 95% CI 0.60-2.07), aflibercept and Ranibizumab (RR 0.77; 95% CI 0.49-1.21), and Bevacizumab and Ranibizumab (RR 0.88; 95% CI 0.60-1.30) showed wide confidence intervals, reflecting substantial imprecision. Certainty of evidence (GRADE) ranged from moderate to low.

CONCLUSION: All anti-VEGF agents stabilize or improve vision in nAMD. Aflibercept may provide the most favorable efficacy-safety balance, Faricimab offers promising durability, and Brolucizumab demonstrates large visual gains with potential safety concerns. Further head-to-head and long-term real-world studies are needed to optimize individualized treatment strategies.},
}

@article {pmid41650065,
year = {2026},
author = {Kong, H and Li, J and Lou, J and Zhang, Y and Li, M and Chen, Y and Wang, Y and Tao, T},
title = {A 2-step, 2-sample Mendelian randomization study of gut microbiota, blood metabolites and dry age-related macular degeneration.},
journal = {Medicine},
volume = {105},
number = {6},
pages = {e47527},
doi = {10.1097/MD.0000000000047527},
pmid = {41650065},
issn = {1536-5964},
support = {Y202148025//Scientific Research Fund of Zhejiang Provincial Education Department/ ; Y202456684//Scientific Research Fund of Zhejiang Provincial Education Department/ ; 2023RC081//Medical Scientific Reasearch Foundation of Zhejiang Province/ ; 2025708925//Medical Scientific Reasearch Foundation of Zhejiang Province/ ; 2024RC-QN-02//Ningbo Health Youth Technical Backbone Talent Development Program/ ; 2023HMJQ25//Zhu Xiu Shan Talent Project of Ningbo No.2 Hospital/ ; },
mesh = {Humans ; Mendelian Randomization Analysis/methods ; *Gastrointestinal Microbiome/genetics ; Genome-Wide Association Study ; *Macular Degeneration/genetics/blood ; Aged ; *Geographic Atrophy/genetics/blood ; },
abstract = {Dry age-related macular degeneration (dAMD) is the leading cause of blindness among elderly people in developed countries. The main objective of this study is to investigate the causal relationship between gut microbiota (GM), blood metabolites, and dAMD among European participants. Based on the genome-wide association analysis database, double sample Mendelian randomization (MR) analysis was performed on GM, blood metabolites, and dAMD. The inverse-variance weighted method is used to estimate the causal relationship between GM, blood metabolites, and dAMD, while multiple methods are employed to eliminate pleiotropy and heterogeneity. A 2-step MR analysis quantitatively assessed the effect of metabolite-mediated GM on dAMD. In MR analysis, 15 GM were found to be associated with increased or decreased risk of dAMD, and 18 blood metabolites were found to be associated with increased or decreased risk of dAMD. Our research also found that the potential association between GM and dAMD may be mediated by blood metabolite levels, specifically, ADpSGEGDFXAEGGGVR levels accounted for 38.9% of the causal pathway from genus Parasutterella to dAMD. Our research findings indicate that certain GM and blood metabolites can affect the onset of dAMD, and increasing the abundance of genus Parasottella can increase the risk of dAMD through the mediation of ADpSGEGDFXAEGGGVR levels.},
}

Humans
Mendelian Randomization Analysis/methods
*Gastrointestinal Microbiome/genetics
Genome-Wide Association Study
*Macular Degeneration/genetics/blood
Aged
*Geographic Atrophy/genetics/blood

@article {pmid41649508,
year = {2026},
author = {Muranyi, DS and Molling, J and Hammer, U and Habermann, A and Lehmann, G and Luci, E and Buchwald, C and Hammer, T},
title = {[Real-life data of the IVI interval after switching to faricimab therapy].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41649508},
issn = {2731-7218},
abstract = {BACKGROUND: For neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME), intravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents currently represents the standard of care. Both treatment intervals and the choice of the optimal agent are critical determinants of therapeutic outcomes.

OBJECTIVE: This study evaluated the effect of switching from established anti-VEGF agents (ranibizumab, bevacizumab or aflibercept) to faricimab on injection intervals in patients with nAMD or DME.

MATERIAL AND METHODS: Data were collected in a routine outpatient ophthalmology practice. Inclusion criteria were: (I) treatment according to a treat-and-extend protocol, (II) at least six intravitreal injections prior to switching to faricimab and (III) at least three subsequent faricimab injections. To assess disease-specific effects, patients were stratified into nAMD and DME subgroups.

RESULTS: A total of 86 patients with a mean of 37 prior injections were included. The mean injection interval before switching to faricimab was 44 days. In the nAMD subgroup (n = 74, mean age 72 years), the interval significantly increased from 46 to 53 days (mean difference 7.45 days, p < 0.05). In the DME subgroup (n = 12, mean age 65 years), the interval significantly increased from 42 to 57 days (mean difference 15.25 days, p < 0.05). The effect size was moderate (Cohen's d = 0.56) with high statistical power (99.93%).

CONCLUSION: Switching to faricimab resulted in a significant extension of treatment intervals in both indications, with patients with DME deriving the greatest benefit. Limitations include the small sample size and potential selection bias. These findings suggest an improved benefit-risk profile through reduced injection frequency. Additional real-world data and meta-analyses may help identify biomarkers to further individualize anti-VEGF therapy in the future.},
}

@article {pmid41648145,
year = {2026},
author = {Patel, MK and Piedade, WP and Famulski, J},
title = {Cdhr1a and pcdh15b link photoreceptor outer segments with inner segment calyceal processes revealing a potential mechanism for cone-rod dystrophy.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2024.07.26.605360},
pmid = {41648145},
issn = {2692-8205},
abstract = {Cone rod dystrophy (CRD) is a macular degeneration disorder characterized by initial cone cell photoreceptor degeneration and subsequently of rod photoreceptors. Mutations in CDHR1, a photoreceptor specific cadherin have been found to be associated with the incidence of cone-rod dystrophy and recapitulated in mouse CDHR1 knockouts. However, the molecular function of CDHR1 remains unknown. CDHR1 has been shown to localize at the leading edge of murine rod nascent outer segment (OS) making junctions to an unknown partner in the inner segment. Using Structured Illumination Microscopy (SIM), we observed that the localization of zebrafish cdhr1a extends from basal nascent OS discs above the periciliary ridge of the inner segment to a considerable length along the OS, akin to calyceal process (CPs). When labeling the CPs using pcdh15b, a CP specific cadherin, we observed that cdhr1a at the leading edge of OS juxtaposes with pcdh15b in the CP. Similar localization patterns were detected in human, macaque, xenopus, ducks, and various rodent PRCs indicating conservation. Importantly, using immunoprecipitation and K652 cell aggregation assays we demonstrate that pcdh15b and cdhr1a can interact and potentially link the OS and CP. To analyze the consequences of OS-CP interactions in CRD, we established a zebrafish cdhr1a mutant line (cdhr1afs*146) and analyzed CRD progression at high temporal resolution. Homozygous cdhr1afs*146 mutants begin to exhibit minor cone OS morphology defects starting at 15 dpf (days post fertilization) and severe OS disruption and cell loss by 3 months. Rod OS defects were delayed until 3-6 months. Furthermore, we show that loss of cdhr1a function leads to disorganization and shortening of CPs coinciding with cone outer OS defects which is significantly exacerbated when combined with the loss of pcdh15b. In conclusion, we propose that cdhr1a and pcdh15b function to link cone OSs with CPs to maintain proper OS homeostasis thus revealing a potential novel mechanism for CRD.},
}

@article {pmid41646887,
year = {2026},
author = {Fabian-Jessing, BK and Askou, AL and Jakobsen, TS and Adsersen, RL and Lindholm, AB and Køllner Bjerre, AK and Alsing, S and Bek, T and Aagaard, L and Corydon, TJ},
title = {AAV-mediated multiple gene therapy combining VEGFA-targeting miR-agshRNAs and PEDF for the suppression of choroidal neovascularization.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {1},
pages = {102833},
pmid = {41646887},
issn = {2162-2531},
abstract = {Common ophthalmic diseases, including age-related macular degeneration (AMD), generally have a complex pathogenesis involving multiple pathways and varying involvement of specific cell types. This provides a strong rationale for developing novel gene therapy platforms that allow cell-specific up- and down-regulation of multiple targets while contained within standard adeno-associated viral vectors (AAVs). Hence, we engineered a tunable expression cassette with two pri-miR-embedded, Ago2-dependent shRNAs (miR-agshRNAs) units enabling dual target silencing, and intron embedment allowing downstream protein expression. With this platform, we demonstrated additive Vegfa knockdown, concurrent silencing of Vegfa and mTOR, and simultaneous expression of pigment epithelium-derived factor (PEDF) from a single promoter. Following the subretinal injection of AAV5 vectors encoding Vegfa-targeting miR-agshRNAs and PEDF into the murine retina, profound Vegfa suppression and strong PEDF expression were observed. Notably, laser-induced choroidal neovascularization (CNV) was significantly reduced in the therapeutic groups, with the multi-targeting vector achieving the highest level of CNV suppression. Collectively, our data demonstrated robust anti-angiogenic effects of multiple gene therapies, suggesting a "one-and-done" AAV-based delivery of cross-species anti-VEGFA RNAi therapeutics together with PEDF as a valuable tool for the management of neovascular AMD (nAMD) and other complex neovascular ocular diseases.},
}

@article {pmid41646664,
year = {2026},
author = {Wang, X and Hoshi, S and Kadomoto, S and Liu, R and Ip, M and Sarraf, D and Sadda, SR and Zhang, Y},
title = {Cuticular Drusen Associated Photoreceptor and RPE Optical Property Perturbation Revealed by Adaptive Optics Scanning Laser Ophthalmoscopy.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.15.26343733},
pmid = {41646664},
abstract = {PURPOSE: To characterize microscopic alteration of photoreceptors and RPE surrounding cuticular drusen in age-related macular degeneration (AMD) using multimodal imaging, including high resolution adaptive optics scanning laser ophthalmoscopy (AOSLO).

METHODS: Eyes with early to intermediate AMD and predominantly cuticular drusen underwent color fundus photography, infrared reflectance, fundus autofluorescence, optical coherence tomography (OCT), and AOSLO. Cuticular drusen were identified using multimodal imaging and classified into three OCT-defined phenotypes. Cone photoreceptor reflectivity was assessed on AOSLO. A subset of eyes underwent longitudinal AOSLO and OCT imaging.

RESULT: Nineteen eyes from 12 subjects aged 70.3 ± 5.8 years were studied. Six eyes had longitudinal follow-up imaging. A total of 3177 cuticular drusen were evaluated and classified into 3 types based on cross sectional OCT imaging. AOSLO revealed corresponding phenotype-dependent cone reflectivity alterations associated with the 3 types of cuticular drusen. Type 1: Maintained cone reflectivity overlying the drusen on a hyporeflective background. Type 2: Cone reflectivity loss overlying the cuticular drusen. Type 3: Cones are predominantly not visible over the cuticular drusen. Lesion diameters were 52.62 ± 9.38 µm (Type 1), 71.88 ± 12.39 µm (Type 2), and 124.72 ± 20.94 µm (Type 3). All lesions were accompanied by hypertransmission in the choroid on OCT. Longitudinal imaging showed that localized outer retinal reflectivity reduction on AOSLO preceded the detection of new cuticular drusen on OCT.

CONCLUSIONS: Cellular-resolution multimodal imaging demonstrates progressive, phenotype-specific disruption of the photoreceptor-RPE complex associated with cuticular drusen in AMD. Early AOSLO-detected reflectivity changes preceding OCT-visible lesions highlight the sensitivity of adaptive optics imaging for identifying early outer retinal alterations and for advancing understanding of the biogenesis of cuticular drusen.},
}

@article {pmid41646411,
year = {2026},
author = {Skowronska-Krawczyk, D and Tom, E and Gao, F and Franco, C and Wong, A and Kemmerer, N and Wang, Z and Xu, Q and Zhuang, Y and Du, S and Palczewska, G and Palczewski, K and Budin, I and Shi, X and Bonilha, V and Schöneberg, J and Wahlin, K and Albrecht, L},
title = {Age-Driven Lipid Remodeling Activates Lysosome-Mediated Plasma Membrane Repair.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8607320/v1},
pmid = {41646411},
issn = {2693-5015},
abstract = {The abundance and stoichiometry of membrane lipid species vary across a cell's lifespan and metabolic state. In the retinal pigment epithelium (RPE), age-related alterations in lipid composition contribute to vision loss and diseases such as age-related macular degeneration (AMD), yet the molecular drivers of these changes remain unclear. Here, we show that age-dependent remodeling of the composition and biophysical properties of the plasma membrane compromises membrane integrity and function. Remarkably, rather than undergoing cell death, affected cells activate a lysosome-dependent plasma membrane repair program to preserve barrier integrity. While this adaptive response may protect RPE structure under metabolic stress, it also drives spatially polarized release of lysosomal contents that potentially can contribute to extracellular matrix remodeling and sub-RPE deposit formation during aging and AMD. Finally, we demonstrate that supplementation with the direct product of the aging-associated lipid elongase ELOVL2 alleviates these phenotypes, providing direct evidence for a critical role of ELOVL2-mediated PUFA elongation in healthy aging. Taken together, our results propose a model in which age-dependent decline in PUFA elongation disrupts the balance between membrane flexibility and stability, initiating a compensatory cycle of membrane stress and repair.},
}

@article {pmid41646332,
year = {2026},
author = {Sadda, S and Huang, J and Nittala, M and Corradetti, G and Chung, YC and Quarta, A and Abbasgholizadeh, R and Soylu, C and Chujo, S and Velaga, SB},
title = {Spatial Distribution of Cuticular Drusen and its Association with Category-Specific Progression Risk in Intermediate AMD.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8504851/v1},
pmid = {41646332},
issn = {2693-5015},
abstract = {Objectives To investigate the spatial distribution pattern of cuticular drusen using en face OCT and determine its relationship with 2-year progression of age-related macular degeneration (AMD). Methods This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enrolled in the Amish Eye Study who completed two years of follow-up. Multimodal imaging, including volume spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three Early Treatment Diabetic Retinopathy Study (ETDRS) grid zones using ImageJ. K-means clustering analysis was used to categorize distribution patterns. Firth's penalized logistic regression evaluated association between cuticular drusen distribution categories and progression to late AMD at 2 years. Results Cuticular drusen exhibited a concentric pattern within 6x6mm macular area. Mean (SD) density was highest in central zone (6.14 (3.89) count/mm2). Cluster analysis classified eyes into predominantly central (57.5%), predominantly peripheral (32.2%), and diffuse (10.3%) categories. Over 2 years, 5 eyes progressed to late AMD, 4 of which belonged to predominantly peripheral group. Firth logistic regression demonstrated that predominantly peripheral category had significantly increased risk of AMD progression compared to low-risk groups (predominantly central and diffuse), with an odds ratio of 7.2 (95% CI: 1.2-74.2, p = 0.027). Conclusions The spatial distribution of cuticular drusen exhibits a concentric, centrally-weighted pattern. A predominantly peripheral distribution of cuticular drusen is significantly associated with progression to late AMD over two years. This quantifiable distribution pattern may serve as a novel high-risk biomarker for advanced AMD.},
}

@article {pmid41643859,
year = {2026},
author = {Castro-Fernández, DC and Cañizo-Outeriño, A and Cuartero-Martínez, A and Gil-Martinez, M and Mondelo-Garcia, C and González-Barcia, M and Álvarez-Barrios, A and Fernández-Ferreiro, A},
title = {A systematic review on age-related macular degeneration: New insights from multi-omics studies.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.02.001},
pmid = {41643859},
issn = {1879-3304},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries and a growing global health concern. The multifactorial nature of AMD calls for integrative multi-omics approaches. We summarize studies employing multi-omics in AMD. A comprehensive search in PubMed and Scopus databases identified 561 records with multi-omics criteria, of which duplicates, unrelated and unavailable articles were excluded, resulting in 33 reports. Quality was assessed following the Office of Health Assessment and Translation (OHAT) method, and data was synthesized through standardized evidence tables. Across the reviewed reports, multi-omics approaches were applied to non-clinical and clinical samples, including ocular and systemic fluids. Methodological trends included the widespread use of causal inference approaches (e.g., Mendelian randomization and Bayesian colocalization) and increasing adoption of spatial and single-cell resolution techniques. Converging molecular patterns consistently suggested inflammation, complement activation, angiogenesis, lipid dysregulation, and mitochondrial dysfunction as key processes underlying AMD. Integration of genetic risk with proteomic and metabolomic alterations, enabled the identification of candidate diagnostic and prognostic biomarkers such as carboxyethylpyrrole and PRMT3. Additionally, this review revealed opportunities for personalized medicine in AMD patient stratification, improvement of prediction models, and therapeutic personalization; however, heterogeneity was noted across studies, particularly regarding sample source (systemic vs. ocular), analytical platforms, integration strategies, and ancestry representation. Despite this variability, this review illustrates how integrating multiple omics layers provides a comprehensive and multidimensional understanding of AMD pathology, advancing research towards better diagnosis, prognosis, and therapeutics for these patients.},
}

@article {pmid41642651,
year = {2026},
author = {Lewis, TR and Castillo, CM and Phan, S and Shores, CR and Hayase, KK and Kim, KY and Ellisman, MH and Alekseev, O and Burns, ME and Arshavsky, VY},
title = {Adam9-deficient retinal pigment epithelium pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion.},
journal = {The Journal of clinical investigation},
volume = {},
number = {},
pages = {},
doi = {10.1172/JCI196705},
pmid = {41642651},
issn = {1558-8238},
abstract = {Vision begins in the outer segment compartment of photoreceptor cells, which is constantly renewed through the addition of membrane material at its base and ingestion of mature membranes at its tip by the retinal pigment epithelium (RPE). The close apposition of outer segments to the RPE is believed to be critical for maintaining this renewal process. Yet, in several retinal diseases, expansion of the subretinal space separating photoreceptors from the RPE does not immediately impact photoreceptor functionality. Here, we analyzed outer segment function and renewal in the Adam9 knockout mouse characterized by a major expansion of the subretinal space. Surprisingly, photoreceptor-RPE separation affected neither the sensitivity of photoreceptor light-responses nor the normal rate of outer segment renewal in this mouse prior to the onset of photoreceptor degeneration. The latter is achieved through the formation of elongated RPE "pseudopods" extending across the enlarged subretinal space to ingest outer segment tips. This work suggests that pseudopod formation may underlie the persistence of photoreceptor function in human diseases accompanied by photoreceptor-RPE separation, such as vitelliform macular dystrophy or age-related macular degeneration associated with subretinal drusenoid deposits.},
}

@article {pmid41642581,
year = {2026},
author = {Bellanda, V and Schulgit, MJ and Barbosa, GCS and Mohan, N and Arline, A and Bala, S and Kaelber, DC and Srivastava, SK and Sharma, S},
title = {Relative Risk of Neovascular Age-Related Macular Degeneration Following Cataract Surgery.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.6048},
pmid = {41642581},
issn = {2168-6173},
}

@article {pmid41642305,
year = {2026},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {How do genetic polymorphisms influence the efficacy of age-related macular degeneration treatments? A systematic review and meta-analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41642305},
issn = {1435-702X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) has considerable global burden, being a major cause of vision loss. Subsequently, genetic predisposition holds a role in this case by contributing to disease susceptibility. Polymorphisms in genes such as Complement Factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2) play a key role as risk factors for AMD. This systematic review and meta-analysis synthesizes existing evidence to investigate and quantify the association between these polymorphisms and the actual risk of AMD. Additionally, the paper sets to unravel the prevalence of high- and low-risk genotypes among AMD patients.

METHODS: In accordance with PRISMA guidelines, we conducted a systematic search of PubMed, Scopus, Web of Science, EMBASE, and the Cochrane Library databases to identify relevant studies. We included primary studies that involved patients diagnosed with AMD and assessed genetic polymorphisms of CFH (Y402H, rs1061170), ARMS2 (A69S, rs10490924), and we included studies evaluating CFH Y402H and ARMS2 A69S in relation to AMD susceptibility and extracted any available data on anti VEGF treatment response for narrative synthesis. The analytical series considered random effects models to perform the associated meta-analyses. Study heterogeneity was assessed using the I² statistic measure as a standard assessment within the studies. The odds ratio (OR) with 95% confidence intervals (CI) was used as the effect measure.

RESULTS: The literature search obtained 1,420 studies from which 10 satisfied the eligibility criterion. The meta-analysis utilized eight studies. The association between CFH Y402H polymorphism and AMD risk indicated that the risk of AMD among risk allele carriers was OR 2.25 (95% CI: 1.27-4.00, p = 0.006). ARMS2 polymorphisms demonstrated a strong genetic association to the risk of AMD with an OR of 4.05 (95% CI: 1.79-9.16, p < 0.001). In the second meta-analysis evaluating genotype prevalence, the random-effects model showed an OR of 1.439 (95% CI: 0.929-2.231, p = 0.103), suggesting a variable but moderate prevalence of high-risk genotypes among AMD patients (I² = 95.7%, p < 0.001).

CONCLUSIONS: This meta-analysis confirms the significant association between CFH and ARMS2 polymorphisms and AMD susceptibility, emphasizing their role in disease pathogenesis. The findings highlight the potential for genetic screening in AMD risk assessment and personalized treatment strategies. However, substantial heterogeneity across studies underscores the need for standardized methodologies and further research into gene-environment interactions. Integrating genetic risk assessment into clinical practice may improve early detection and targeted interventions for AMD.},
}

@article {pmid41642030,
year = {2026},
author = {Su, IL and Yeh, KL and Lee, CY and Lin, SC and Chiang, CY and Chen, CJ and Chen, WY and Tseng, CC and Lu, YC and Kuan, YH},
title = {Irigenin Modulates BL-Induced Pyroptosis in Retinal Pigment Epithelial Cells Through p38 MAPK and NFκB Pathways.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {2},
pages = {e70723},
doi = {10.1002/jbt.70723},
pmid = {41642030},
issn = {1099-0461},
support = {NSTC113-2320-B-040-014-MY3//National Science and Technology Council, Taiwan/ ; NCHU-CSMU-11408//National Chung Hsing University and Chung Shan Medical University/ ; R110-030//Ditmanson Medical Foundation Chia-Yi Christian Hospital Research Program/ ; CSMU-TSMH-112-02//Chung Shan Medical University and Antai Medical Care Cooperation Antai Tian-Sheng Memorial Hospital/ ; },
mesh = {Humans ; *Pyroptosis/drug effects/radiation effects ; *NF-kappa B/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *p38 Mitogen-Activated Protein Kinases/metabolism ; *Isoflavones/pharmacology ; Cell Line ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; *Epithelial Cells/metabolism/pathology/drug effects ; Inflammasomes/metabolism ; Signal Transduction/drug effects ; *MAP Kinase Signaling System/drug effects ; },
abstract = {Age-related macular degeneration (AMD), a primary cause of vision loss among older adults, is strongly associated with inflammatory processes. The current study aimed to elucidate the protective effects of irigenin, an isoflavonoid recognized for its anti-inflammatory, antioxidative, antiapoptotic, and anticancer activities, against blue light (BL)-induced damage in N-retinyl-N-retinylidene ethanolamine (A2E)-laden human adult retinal pigment epithelial (A2E-laden ARPE-19) cells. Pretreatment with irigenin markedly mitigated BL-induced cytotoxicity and preserved epithelial barrier function in a concentration-dependent manner. Moreover, irigenin significantly inhibited the expression of proinflammatory cytokines and activation of the nod-like receptor pyrin domain-containing 3 (NLRP3) inflammasome, as evidenced by decreased expression of NLRP3, ASC, and both full-length and cleaved forms of gasdermin D (GSDMD), along with reduced caspase-1 activity. Further mechanistic analyses indicated that irigenin effectively suppressed the activation of the nuclear factor kappa B (NFκB) signaling pathway, as evidenced by phosphorylation of NFκB and inhibitor of NFκB (IκB)α, and both activation and translocation of NFκB, along with reduced phosphorylation of p38 mitogen-activated protein kinase (MAPK). These findings underscore the potential of irigenin to ameliorate BL-induced retinal pigment epithelial cell damage via modulation of inflammation and pyroptosis pathways, suggesting its therapeutic value for preventing AMD.},
}

Humans
*Pyroptosis/drug effects/radiation effects
*NF-kappa B/metabolism
*Retinal Pigment Epithelium/metabolism/pathology/drug effects
*p38 Mitogen-Activated Protein Kinases/metabolism
*Isoflavones/pharmacology
Cell Line
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
*Epithelial Cells/metabolism/pathology/drug effects
Inflammasomes/metabolism
Signal Transduction/drug effects
*MAP Kinase Signaling System/drug effects

@article {pmid41641862,
year = {2026},
author = {Chambon, C and Picard, E and Zola, M and Aichedo, S and Lebon, C and Youale, J and Matet, A and Bousquet, E and Ferreira, C and Kowalczuk, L and Théron, L and Behar-Cohen, F},
title = {Proteomic Signature in Men with Central Serous Chorioretinopathy.},
journal = {Journal of proteome research},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jproteome.5c01233},
pmid = {41641862},
issn = {1535-3907},
abstract = {To explore systemic contributors to central serous chorioretinopathy (CSCR) pathogenesis, we performed untargeted serum proteomics in 60 male CSCR patients (30 acute, 30 chronic) and 60 age-matched controls using label-free LC-MS/MS with stringent statistical pairing. Among 242 abundant proteins identified, 27 (11.5%) were significantly different in CSCR, converging on pathways of complement activation, coagulation, oxidative stress, immune regulation, and response to external stimuli. Complement cascade components (C1QA, C1S, C3, C4B, C8A/B/G, CFB) were upregulated, while the regulators CFHR1 and CFHR2 were decreased, contrary to age-related macular degeneration. Oxidative stress-related proteins (haptoglobin, hemoglobin subunits, peroxiredoxin-2) were elevated, consistent with prior evidence of systemic redox imbalance in CSCR. Tetranectin (CLEC3B) decreased and attractin (ATRN) increased in CSCR were validated by ELISA. Multiplex immunofluorescence on the human retina localized tetranectin to Müller cells, including the outer limiting membrane, and to the RPE and attractin to photoreceptor segments, retinal pigment epithelium, Bruch's membrane, and the choriocapillaris, supporting potential roles of both proteins at the retina-choroid interface. A distinct systemic proteomic signature in patients with CSCR highlights complement dysregulation, oxidative stress, and stress responses to external stimuli and identifies tetranectin and attractin as candidate biomarkers, which should further be validated in other cohorts.},
}

@article {pmid41641772,
year = {2026},
author = {Salkar, A and Palanivel, V and Basavarajappa, D and Heng, B and Schulz, A and Gupta, V and Graham, S and Mirzaei, M and You, Y},
title = {Retinal glial cells in glaucoma and age-related retinal diseases: Inflammatory responses, disease transitions, and translational perspectives.},
journal = {Neural regeneration research},
volume = {},
number = {},
pages = {},
doi = {10.4103/NRR.NRR-D-25-01905},
pmid = {41641772},
issn = {1673-5374},
abstract = {Microglia, Müller cells, and astrocytes play a crucial role in maintaining retinal structure, homeostasis, and neuronal function. In disease, they undergo reprogramming that drives chronic inflammation and neurodegeneration. Unique to the retina, these glial cells occupy specialized niches and interact closely with the blood-retinal barrier, creating distinct vulnerabilities. We summarized the glial activation mechanisms, shared triggers, including oxidative stress, metabolic dysfunction, aging, and systemic inflammation, as well as key pathways, such as nuclear factor kappa-B, mitogen-activated protein kinase, Janus kinase/signal transducer and activator of transcription, the inflammasome, and the complement system. Disease-specific responses in glaucoma, age-related macular degeneration, diabetic retinopathy, and vascular occlusions were compared, highlighting the heterogeneity of gliosis and its impact on neuronal and vascular pathology. We also discussed emerging human-derived platforms alongside proteomics approaches, highlighting their utility for mechanistic insights and discovering biomarkers. Despite advances, critical gaps remain in understanding glial-glial interactions and in developing robust models focused on glia. Despite these advances, major gaps remain in our understanding of glial-glial communication, state transitions, and their temporal relationship to neurodegeneration. Moreover, the lack of experimental models explicitly designed to interrogate glial biology continues to limit translational progress. Addressing these challenges will be essential to reposition glial cells as central drivers of retinal disease rather than secondary responders. A strategic shift toward glia-centered models, integrative multi-omics analyses, and human-relevant systems holds promise for advancing biomarker discovery and developing targeted therapeutic strategies that aim to modulate glial dysfunction and preserve vision.},
}

@article {pmid41641466,
year = {2026},
author = {Veerman, D and Cuartas-Vélez, C and Gensheimer, T and van Dorp, T and van der Meer, A and Bosschaart, N},
title = {Label-free assessment of a microfluidic vessel-on-chip model with visible-light optical tomography reveals structural changes in vascular networks.},
journal = {Lab on a chip},
volume = {},
number = {},
pages = {},
pmid = {41641466},
issn = {1473-0189},
abstract = {Microvascular dysfunction is characterized by impaired structure and function of small blood vessels, contributing to disease-related tissue and organ damage, such as in the retina. Optical coherence tomography is a widely used clinical technology to detect, monitor and diagnose disorders of the retina and choroid, such as diabetic retinopathy, macular degeneration, and various inherited retinal diseases. Currently, there are limited experimental platforms that correlate observed changes in clinical metrics with underlying mechanisms of disease progression. Organ-on-chips have the potential to offer a platform for correlative studies. Previous studies have demonstrated that the three-dimensional complexity of the microvasculature can be captured in a vessel-on-chip. Yet, current vessel-on-chip imaging analysis is based on end-point read-outs that provide limited dynamic information and do not have direct correlation with imaging techniques used in the clinic. Therefore, there is a need for clinically relevant, label-free, real-time imaging technologies. In this work, we show that optical coherence tomography can fulfill this need by providing non-invasive, label-free imaging of vascular networks-on-chip. We show that optical coherence tomography can detect and can be used to quantify changes in vascular network structures over multiple days, both during vascular network development and in response to disease-associated conditions. Our results indicate that optical coherence tomography has the potential to become a standard read-out for monitoring dynamic processes in organ-on-chips. In the future, these read-outs may enable the correlation of clinical metrics, thereby providing deeper insights in the pathophysiology of diseases, for example of the retina.},
}

@article {pmid41641369,
year = {2026},
author = {Wang, N and Luo, L and Yang, X},
title = {The gut-eye axis in age-related macular degeneration: from microbial dysbiosis to targeted intervention strategies.},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {251},
number = {},
pages = {10876},
pmid = {41641369},
issn = {1535-3699},
mesh = {Humans ; *Macular Degeneration/microbiology/therapy ; *Gastrointestinal Microbiome/physiology ; *Dysbiosis/microbiology/complications/therapy ; Fecal Microbiota Transplantation ; Probiotics/therapeutic use ; Animals ; Prebiotics ; },
abstract = {Age-related macular degeneration (AMD) represents a leading cause of irreversible blindness among the older persons. Characterized by a complex pathogenesis and multiple risk factors, AMD poses substantial challenges for treatment and has emerged as a significant public health concern. The gut microbiota constitutes a vast and dynamically evolving ecosystem, with a healthy microbial community playing an essential role in maintaining host homeostasis through its involvement in digestion and immune defense. However, alterations in microbial composition or function can compromise intestinal barrier integrity, trigger systemic inflammation, and contribute to disease pathogenesis. Evidence now underscores the influence of gut microbiota on the development and progression of AMD. This review examines the mechanisms by which gut microbes may contribute to AMD pathogenesis and evaluates the therapeutic potential of interventions targeting the gut microbiome-including dietary modifications, Pharmacological and Biological Agents, probiotics, prebiotics, and fecal microbiota transplantation-for AMD management.},
}

Humans
*Macular Degeneration/microbiology/therapy
*Gastrointestinal Microbiome/physiology
*Dysbiosis/microbiology/complications/therapy
Fecal Microbiota Transplantation
Probiotics/therapeutic use
Animals
Prebiotics

@article {pmid41638748,
year = {2026},
author = {Vougioukalou, S and Read, SM and Csontos, JK and Jones, A and Jaber, A and Sharma, A and Balaskas, K},
title = {Comparing community-based monitoring to hospital-based care of patients with quiescent age-related macular degeneration: a qualitative study of patient and practitioner perspectives on acceptability and access.},
journal = {BMJ open},
volume = {16},
number = {2},
pages = {e101379},
doi = {10.1136/bmjopen-2025-101379},
pmid = {41638748},
issn = {2044-6055},
mesh = {Humans ; Qualitative Research ; Female ; Aged ; Male ; *Macular Degeneration/therapy ; *Community Health Services ; *Patient Acceptance of Health Care ; *Attitude of Health Personnel ; *Health Services Accessibility ; Aged, 80 and over ; Middle Aged ; Patient Satisfaction ; Hospitals ; },
abstract = {OBJECTIVES: This process evaluation explores patient and healthcare professional acceptability of community-based monitoring versus hospital-based care for patients with quiescent neovascular age-related macular degeneration (QnAMD).

DESIGN: Qualitative process evaluation was conducted as part of a randomised controlled trial.

SETTING: Six hospitals and six community-based practices.

PARTICIPANTS: 25 patients and 16 healthcare professionals (ophthalmologists and optometrists). This approach helped differentiate between common issues and those specific to community-based monitoring.

INTERVENTION: The Quality-Assured Follow-Up of QnAMD by non-medical practitioners trial aimed to examine whether non-medical practitioners follow-up patients with QnAMD in the community in a safe and clinically and cost-effective way. The process evaluation aimed to examine whether the intervention was acceptable by patients and professionals. The process evaluation was based on interviews which contained open-ended questions focused on patient experience and confidence in community-based care, issues concerning the practicalities of the organisation and management of the clinic, and resources including IT and digital equipment. The theory of acceptability framework was used to interpret the findings.

RESULTS: Patients reported positively on the experience of receiving QnAMD services in the community and highlighted staff professionalism and clear communication. Key themes were the proximity of care provision for patients, IT interoperability and the real-world costs of running the service. Some patients randomised to the hospital showed preference for the intervention to take place in the hospital, mediated mainly by prior experience of hospital care and travel distance. The location of the clinic and transport routes affected the experience of attending appointments, with strong preference expressed for proximity to one's home. Inaccessibility due to non-modifiable internal building structures in the community and parking in hospital eye services was reported by a small proportion of patients. Healthcare professionals reported positively about their ability to deliver QnAMD services in community settings but raised concerns about the compatibility of technological infrastructure that facilitates the sharing of optical coherence tomography image and video files. Some optometrists were also concerned about the financial sustainability of the intervention after the end of the trial due to the costs involved in the administration of QnAMD follow-up care.

CONCLUSIONS: The delivery of QnAMD services in the community by non-medical personnel was broadly accepted by both patients and practitioners. This implies that non-medical practitioners can follow up patients with QnAMD in the community in a safe way. Further research would be needed to establish whether similar results would be obtained during routine practice outside a research project and whether the long-term follow-up for QnAMD would be financially sustainable for independent as well as chain community optometry practices.

TRIAL REGISTRATION NUMBER: NCT03893474.},
}

Humans
Qualitative Research
Female
Aged
Male
*Macular Degeneration/therapy
*Community Health Services
*Patient Acceptance of Health Care
*Attitude of Health Personnel
*Health Services Accessibility
Aged, 80 and over
Middle Aged
Patient Satisfaction
Hospitals

@article {pmid41638110,
year = {2026},
author = {Amin, R and Kaiser, PK},
title = {Tyrosine kinase inhibitors for wet age-related macular degeneration: The current developmental landscape.},
journal = {The Journal of pharmacology and experimental therapeutics},
volume = {393},
number = {3},
pages = {103803},
doi = {10.1016/j.jpet.2026.103803},
pmid = {41638110},
issn = {1521-0103},
abstract = {Age-related macular degeneration (AMD) is a leading cause of permanent vision loss in older patients worldwide. The neovascular (wet) AMD is characterized by abnormal choroidal neovascularization driven by vascular endothelial growth factor (VEGF), platelet-derived growth factor, and Tie2 signaling pathways, leading to retinal damage and progressive vision decline. Current standard-of-care anti-VEGF therapies aim to limit choroidal neovascularization through extracellular targeting of cytokines involved in the VEGF signaling pathway implicated in angiogenesis. Although these existing therapies can be effective, many patients face a high treatment burden of multiple intraocular injections, which can negatively impact compliance, safety, and long-term efficacy. Tyrosine kinase inhibitors (TKIs) aim to address these limitations by offering longer durability, broad-spectrum targeting of angiogenic pathways, and a reduction in treatment burden through intracellular targeting of angiogenic pathways. With multiple pharmaceutical TKI candidates advancing through clinical trials and showing promising data, this class of drugs could lead to a shift in future treatment options for patients with wet AMD. Despite the progress TKIs have made, there have yet to be any candidates approved for wet AMD treatment. Much of the existing evidence is from early-phase and short-term studies, and questions remain about long-term efficacy and safety compared to current standard-of-care anti-VEGF therapies. Nevertheless, with multiple candidates advancing through phase III clinical trials, TKIs have the potential to emerge as a next-generation treatment class that may transform the wet AMD therapeutic landscape. SIGNIFICANCE STATEMENT: Given the chronic nature of wet age-related macular degeneration and the limitations of current anti-vascular endothelial growth factor therapies, tyrosine kinase inhibitors have emerged as a promising class of anti-angiogenic agents. This review highlights the recent clinical developments in this evolving therapeutic landscape.},
}

@article {pmid41636834,
year = {2026},
author = {Mesfin, Y and Salvi, A and Arnal, L and Langlotz, C and Mahajan, V and Ludwig, CA},
title = {Shaping the future of myopia: artificial intelligence for vitreoretinal complications of high and pathologic myopia.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41636834},
issn = {1435-702X},
support = {E. Matilda Ziegler Foundation for the Blind//E. Matilda Ziegler Foundation for the Blind/ ; NEI P30-EY026877//Stanford P30 Vision Research Core Grant/ ; K23EY035741//National Eye Institute K23 Grant/ ; Research to Prevent Blindness, Inc//Research to Prevent Blindness, Inc/ ; },
abstract = {PURPOSE: The global impact of myopia extends far beyond individual ocular health, posing significant challenges to healthcare systems worldwide. Artificial intelligence (AI), particularly deep learning (DL) applied to ophthalmic imaging, offers a promising strategy to ease constraints posed by the myopia epidemic by detecting subtle structural changes early. Here we describe the current literature on AI for detecting retinal sequelae of myopia, including retinal detachments (RD), myopic macular degeneration (MMD), and myopic traction maculopathy (MTM), with attention to imaging modality and model task (classification vs. segmentation).

METHODS: A literature search was conducted to identify studies using DL to detect RD, MMD, and MTM across ophthalmic imaging modalities (including OCT and fundus photography, and where available fluorescein angiography and ultrasonography).

RESULTS/FINDINGS: We reviewed 28 studies that piloted DL models usingclassification and/or segmentation approaches for RD (10 studies), MMD (12 studies), and MTM (6 studies). Reported performance for RD ranged from area under the curve (AUC) 86-100%, accuracy 79.3-98.9%, sensitivity 77.1-97.6%, and specificity 79.7-100%. For MMD, performance ranged from AUC 86-100%, accuracy 85.3-99.8%, sensitivity 37.1-97.8%, and specificity 91.5-99.9%. For MTM, performance ranged from AUC 93.8-99.7%, accuracy 94.3-99.3%, sensitivity 74.5-98.4%, and specificity 84.8-99.7%. Across studies, there was substantial heterogeneity in case definitions, datasets, and evaluation methods, and external validation was inconsistently reported. Many earlier studies used CNN-based architectures, while more recent work increasingly incorporates transformer-based backbones and pretrained or foundation models.

CONCLUSION: Researchers have demonstrated excellent results for developing DL models that accurately classify and segment retinal pathologies associated with myopia. However, despite strong performance, additional work is needed to translate these models into clinical use, including robust external validation, calibration for clinical decision-making, and prospective evaluation, particularly for longitudinal prognostication of incident complications in pathologic myopia.},
}

@article {pmid41636413,
year = {2026},
author = {Cinque, F and Pas, JAAH and de Breuk, A and Heesterbeek, T and Klaver, CCW and Hoyng, CB and Lechanteur, YTE and van Heugten, CM},
title = {Visual Acuity Provides a More Meaningful Measure of Vision-Related Functioning Than Mesopic Microperimetry in Age-Related Macular Degeneration Patients: A Cross-Sectional Study.},
journal = {Translational vision science & technology},
volume = {15},
number = {2},
pages = {5},
doi = {10.1167/tvst.15.2.5},
pmid = {41636413},
issn = {2164-2591},
mesh = {Humans ; Cross-Sectional Studies ; *Visual Acuity/physiology ; Female ; Male ; *Visual Field Tests/methods ; Aged ; *Macular Degeneration/physiopathology/diagnosis ; *Visual Fields/physiology ; *Mesopic Vision/physiology ; Aged, 80 and over ; Middle Aged ; Retina/physiopathology ; Surveys and Questionnaires ; },
abstract = {PURPOSE: Mesopic microperimetry is a promising tool to evaluate retinal function in clinical trials. Although visual function (VF), the ability to perform vision-related tasks, relates strongly to visual acuity (VA) in patients with age-related macular degeneration, the relationship between mesopic microperimetry and VF remains unclear.

METHODS: A cross-sectional study in patients with age-related macular degeneration was performed. VF was measured by questionnaire using a subset of the National Eye Institute 25-Item Visual Function Questionnaire. The macular integrity assessment microperimeter, was used with a 4-2 staircase strategy with a 10° diameter circular grid containing 37 loci. Three interpretations of the retinal sensitivity data were calculated: the mean of the 37 thresholds (mean sensitivity [MS]), the percent-reduced threshold (PRT), and the log-transformed candela mean (MS cd log). MS, PRT, and MS cd log were tested via stepwise hierarchical linear regression and R2.

RESULTS: We analyzed data from 102 patients (64 females [61%]; mean age, 71.8 ± 11.2 years). VF was explained best by VA (MS; R2 VA = 0.38, MS cd log; R2 VA = 0.38, PRT; R2 VA = 0.39). All retinal sensitivities contributed significantly to total R2. In the MS cd log model (total adjusted R2 = 0.52) the combined contribution of variance explained by VA and MS cd log was 46% (partial adjusted R2 = 0.46).

CONCLUSIONS: Mesopic microperimetry is associated with VF but VA provides a more meaningful estimation of this same construct. These results suggest that VA provides stronger evidence of clinical efficacy.

TRANSLATIONAL RELEVANCE: This study relates functional tests to daily vision-related functioning.},
}

Humans
Cross-Sectional Studies
*Visual Acuity/physiology
Female
Male
*Visual Field Tests/methods
Aged
*Macular Degeneration/physiopathology/diagnosis
*Visual Fields/physiology
*Mesopic Vision/physiology
Aged, 80 and over
Middle Aged
Retina/physiopathology
Surveys and Questionnaires

@article {pmid41632207,
year = {2026},
author = {Daskoulidou, N and Nimmo, J and Bright, M and Yang, Z and Nicholls, LE and Morgan, BP and Daskoulidou, N and Zelek, WM},
title = {Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.},
journal = {Mammalian genome : official journal of the International Mammalian Genome Society},
volume = {37},
number = {1},
pages = {33},
pmid = {41632207},
issn = {1432-1777},
abstract = {The brain and eye share striking anatomical, physiological, and immunological similarities. Both are protected by specialised vascular barriers, the blood-brain barrier (BBB) and blood-retinal barrier (BRB) respectively, that maintain homeostasis through tightly regulated cellular and molecular mechanisms. Increasing evidence implicates complement dysregulation as a key driver of neurodegeneration in both organs, contributing to disorders such as Alzheimer’s disease (AD), and age-related macular degeneration (AMD). Genetic and molecular studies highlight overlapping mechanisms, with variants in complement regulators influencing susceptibility to both retinal and brain pathologies. Locally synthesised complement components modulate glial activation, vascular integrity, and synaptic remodelling at both sites and, when dysregulated, contribute to chronic inflammation, synapse loss and neuronal degradation. Despite these shared pathways, therapeutic development has progressed asymmetrically; several complement therapeutics are already in the clinic for AMD and other ocular pathologies, while none are yet in use for brain diseases. This is in part a consequence of the accessibility of the eye where complement targeted drugs can be directly delivered and impact on pathology monitored, difficult in the brain. Lessons learned from the eye, including local delivery to overcome challenges of barrier penetration, may help accelerate development of complement therapeutics for the brain. Here we present a brief perspective that integrates current understanding of complement-mediated mechanisms across brain and eye, emphasising clues from convergent pathophysiology and ocular translational successes.},
}

@article {pmid41636066,
year = {2026},
author = {Lei, Y and Yang, J and Li, Y and Xiao, B and Lai, D and Qiu, Q},
title = {Radiotherapy for Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/02713683.2026.2621179},
pmid = {41636066},
issn = {1460-2202},
abstract = {PURPOSE: Anti-vascular endothelial growth factor (anti-VEGF) drugs have limitations in the treatment of neovascular age-related macular degeneration (nAMD). This study aims to evaluate the efficacy and safety of radiotherapy combined with anti-VEGF therapy versus anti-VEGF monotherapy in the treatment of nAMD.Methods: This systematic review and meta-analysis (PROSPERO registration number: CRD420251010811) searched PubMed, Embase, Cochrane, Web of Science, LILACS, ISRCTN registry, and ClinicalTrials.gov up to February 25, 2025. Two radiotherapy modalities were analyzed: epimacular brachytherapy (EBM) and stereotactic radiotherapy (SRT). The primary outcome was the proportion of participants who lost more than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at 12 and 24 months. A total of four studies were included, yielding 7 articles for meta-analysis.

RESULTS: For EBM combined with anti-VEGF therapy, compared with anti-VEGF monotherapy, there was a higher risk of losing more than 15 ETDRS letters at 12 months (relative risk [RR] 2.36, 95% confidence interval [CI] 1.49-3.74) and 24 months (RR 2.39, 95% CI 1.68-3.39). The difference in best-corrected visual acuity (BCVA) was 0.10 logarithm of the minimum angle of resolution (logMAR) (95% CI 0.05-0.15) at 12 months and 0.17 logMAR (95% CI 0.13-0.21) at 24 months. For SRT combined with anti-VEGF therapy, there was a greater risk of losing more than 15 ETDRS letters at 24 months (RR 1.75, 95% CI 1.12-2.74) compared with anti-VEGF monotherapy; however, the SRT group required 2.10 fewer ranibizumab injections than the sham-irradiation group (mean difference [MD] -2.10, 95% CI -2.97 to -1.22).

CONCLUSION: Epimacular brachytherapy (EBM) combined with anti-VEGF therapy may worsen patient outcomes and increase the risk of adverse events. In contrast, stereotactic radiotherapy (SRT) combined with anti-VEGF therapy does not improve visual acuity but can reduce the frequency of anti-VEGF injections, potentially alleviating the treatment burden for patients with nAMD.},
}

@article {pmid41634482,
year = {2026},
author = {Grimaldi, G and Bartolomeo, N and Garweg, JG and Pfister, IB and Schild, C and Peyla, A and Tillmann, A and De Oliveira Figueiredo, EC and Spitznagel, T and Kitay, AM and Gabathuler, F and Zweifel, S and Kurz-Levin, MM and Ebneter, A and Somfai, GM and Eandi, CM and Munk, MR and Ambresin, A and Menghini, M},
title = {One-Year Real-World Outcomes of Aflibercept 8 mg in Treatment-Naïve Neovascular Age-Related Macular Degeneration: A Swiss Retina Research Network Report.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41634482},
issn = {2193-8245},
abstract = {INTRODUCTION: This study reports the 1-year efficacy of aflibercept 8 mg (afl8) in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

METHODS: An observational, retrospective case series from nine centers of the Swiss Retina Research Network including treatment-naïve eyes with nAMD started on intravitreal afl8. Changes in visual acuity (VA), macular thickness, pigment epithelial detachment (PED) height, and retinal fluids were evaluated over 12 months and compared with baseline. Treatment intervals and safety data were recorded along with subgroup analyses based on macular neovascularization type, loading-phase completion, and treatment regimen.

RESULTS: A total of 91 eyes met the inclusion criteria. After 1 year of treatment, VA changed by + 1.0 ± 13.2 letters (p = 0.018), mean CST changed by -110.0 ± 130.9 µm (p < 0.001), and mean PED height changed by -71.2 ± 104.8 µm (p < 0.001). After 12 months, 66.2% of eyes demonstrated a complete absence of macular fluids. Mean treatment interval was 13.9 ± 7.9 weeks, with 56.1% of eyes being extended to ≥ 12 weeks with an anatomy-driven approach. No functional or anatomical differences were observed between eyes receiving a clean loading phase and in terms of different macular neovascularization (MNV) subtypes. Two adverse events were observed.

CONCLUSIONS: The first 1-year real-world experience with afl8 in patients with nAMD revealed a robust anatomical response but only a variable and limited visual gain over 12 months due to a ceiling effect. Our findings confirm the fast and sustained macular drying reported from clinical trials, allowing for extended treatment intervals without compromising safety and efficacy.},
}

@article {pmid41634481,
year = {2026},
author = {Cheung, CMG and Kikushima, W and Teo, KYC},
title = {Initial Experiences of Switching to Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration and Polypoidal Chorodal Vasculopathy in an Asian Population.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41634481},
issn = {2193-8245},
support = {NMRC/LCG23 May/0032//National Medical Research Council Singapore Open Fund Large Collaborative Grant/ ; 24-Jan-0005//STaR/ ; },
abstract = {INTRODUCTION: Recent advances in the development of antivascular endothelial growth factor (VEGF) therapy for neovascular age-related macular degeneration (nAMD) include the approval of aflibercept 8 mg, which delivers four times the previously commercially available dose. A longer durability of aflibercept 8 mg compared with 2 mg was reported in the clinical trial results. However, there are limited data in patients switching to aflibercept 8 mg from other agents in clinical practice. This study reports the initial real-world experience of consecutive patients switched to aflibercept 8 mg.

METHODS: Consecutive eyes with previously treated nAMD receiving aflibercept 8 mg switched from other agents were retrospectively reviewed. Patients were switched either owing to suboptimal control of disease activity (efficacy group) or to potentially extend treatment intervals (durability group). The main outcome measures included change in optical coherence tomography (OCT)-based anatomical parameters, including central subfield thickness (CST) and presence of subretinal fluid (SRF), intraretinal fluid (IRF), and pigment epithelial detachment (PED) before and after switching. In addition, quantification of OCT biomarkers was performed using the RetinAI Discovery algorithm.

RESULTS: A total of 30 eyes from 29 patients were identified. Among the 25 eyes in the efficacy group, 20 eyes remained on aflibercept 8 mg through to the last follow-up visit. Median CST showed a significant reduction from 291 (275-301) µm to 279 (269-289) µm (p = 0.02). Volumetric analysis showed a significant reduction in SRF volume, a small nonsignificant increase in IRF volume, and a trend toward reduction in PED volume. The five eyes in the durability group had no SRF, IRF, or hemorrhage at the time of switching and remained stable during the follow-up period.

CONCLUSIONS: These results provide early experience of aflibercept 8 mg in a clinical cohort in hard-to-treat patients. The current analysis demonstrated favorable anatomical outcomes after switching in most patients, with no safety signals.},
}

@article {pmid41633708,
year = {2026},
author = {Romdhoniyyah, DF and Alshukri, A and Parry, DG and Harding, S and Beare, NAV},
title = {Metformin and incidence of age-related macular degeneration in people with diabetes: a population-based 5-year case-control study.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {1},
pages = {},
doi = {10.1136/bmjophth-2025-002339},
pmid = {41633708},
issn = {2397-3269},
mesh = {Humans ; *Metformin/therapeutic use ; *Macular Degeneration/epidemiology/diagnosis/prevention & control ; Male ; Female ; Incidence ; *Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology ; Aged ; Case-Control Studies ; Middle Aged ; *Hypoglycemic Agents/therapeutic use ; Disease Progression ; *Diabetic Retinopathy/drug therapy/diagnosis/epidemiology ; Follow-Up Studies ; },
abstract = {OBJECTIVE: Metformin has been identified as a potential treatment for age-related macular degeneration (AMD). Photographic screening for diabetic retinopathy provides an opportunity to conduct a case-control study with systematic AMD grading. We aimed to investigate associations between metformin use and incidence and progression of AMD at different grades.

METHODS AND ANALYSIS: We randomly sampled 2600 participants from 10 336 people aged ≥50 years with diabetes who attended retinopathy screening in 2011 (baseline) and were enrolled to the Individualised Screening for Diabetic Retinopathy study. 2545 of these participants had type 2 diabetes and gradable fundus photographs at baseline, which were graded using modified age related eye disease study grading. We used data including those on metformin prescription from general practitioner records. We used multivariate logistic regression to investigate associations between metformin and incidence or progression of early, intermediate and late AMD.

RESULTS: Of 2545 participants, 2089 attended and had gradable fundus images on year 5. Metformin was associated with reduced incidence of intermediate AMD by 5 years after adjusting for confounders (complete record OR 0.63, 95% CI 0.43 to 0.92, p=0.02). In univariate analysis, metformin was associated with reduced incidence of late AMD (OR 0.43, 95% CI 0.21 to 0.88, p=0.02) but this did not remain significant after adjusting for age and sex. The numbers progressing to late AMD were small. There was no association between metformin and the incidence of early AMD.

CONCLUSION: We have found a significant association between metformin use and reduction in incidence of intermediate AMD by 37% in people with diabetes over 5 years. Previous epidemiological studies of metformin and AMD have used secondary data on AMD. In this observational study, there were baseline differences between groups, although significant findings remained after adjusting for important confounders. Given metformin's anti-ageing therapeutic effects, the reduction in risk is plausible and warrants prospective clinical trials.},
}

Humans
*Metformin/therapeutic use
*Macular Degeneration/epidemiology/diagnosis/prevention & control
Male
Female
Incidence
*Diabetes Mellitus, Type 2/drug therapy/complications/epidemiology
Aged
Case-Control Studies
Middle Aged
*Hypoglycemic Agents/therapeutic use
Disease Progression
*Diabetic Retinopathy/drug therapy/diagnosis/epidemiology
Follow-Up Studies

@article {pmid41633707,
year = {2026},
author = {Patel, SS and Boyer, DS and Loewenstein, A and Clark, J and Zhu, L and Tang, J and Desai, D},
title = {Safety and tolerability of avacincaptad pegol in combination with ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration: results from a phase 1 and phase 2a study.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {1},
pages = {},
doi = {10.1136/bmjophth-2025-002232},
pmid = {41633707},
issn = {2397-3269},
mesh = {Humans ; *Ranibizumab/administration & dosage/adverse effects/pharmacokinetics ; Male ; Female ; Aged ; Intravitreal Injections ; *Visual Acuity ; Angiogenesis Inhibitors/administration & dosage/adverse effects ; Drug Therapy, Combination ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; *Polyethylene Glycols/administration & dosage/pharmacokinetics/adverse effects ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Dose-Response Relationship, Drug ; Tomography, Optical Coherence ; },
abstract = {OBJECTIVE: To assess the safety and tolerability of avacincaptad pegol (ACP), a Food and Drug Administration-approved therapy for geographic atrophy, administered in combination with ranibizumab, an approved therapy for neovascular age-related macular degeneration (nAMD), in patients with nAMD.

METHODS: The phase 1 study (NCT00709527) was a two-part, ascending-dose and parallel-group, open-label trial that assessed the safety, tolerability and pharmacokinetic profile of monthly intravitreal injections of ACP (0.03, 0.3, 1, 2, 3 mg) in combination with ranibizumab (0.5 mg) on the same day in treatment-naïve patients with nAMD (n=43 patients received a maximum of 6 injections). The phase 2a study (NCT03362190) was an open-label trial assessing the 6-month safety of intravitreal injections of ACP administered in combination with ranibizumab in treatment-naïve patients with nAMD (n=64). Patients received either ACP 2 mg or 4 mg either 14 days or 1 month apart, given on the same day or 2 days after ranibizumab. Primary outcome measures were safety and tolerability.

RESULTS: During the phase 1 study, there were no dose-limiting toxicities at any dose level. In both studies, ocular treatment-emergent adverse events were mostly mild or moderate, with the most reported events related to the injection procedure. There were no clinically significant increases in intraocular pressure or cumulative increases with multiple injections over time. There were no safety issues identified through measurement of visual acuity.

CONCLUSIONS: Coadministration of ACP and ranibizumab in treatment-naïve patients with nAMD was well tolerated across different dosing regimens with no new safety issues based on results from two independent studies.},
}

Humans
*Ranibizumab/administration & dosage/adverse effects/pharmacokinetics
Male
Female
Aged
Intravitreal Injections
*Visual Acuity
Angiogenesis Inhibitors/administration & dosage/adverse effects
Drug Therapy, Combination
*Wet Macular Degeneration/drug therapy/diagnosis/physiopathology
*Polyethylene Glycols/administration & dosage/pharmacokinetics/adverse effects
Aged, 80 and over
Treatment Outcome
Middle Aged
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Dose-Response Relationship, Drug
Tomography, Optical Coherence

@article {pmid41633199,
year = {2026},
author = {Hayashi, K and Kobayashi, M and Mori, K and Nakagawa, Y and Watanabe, B and Masuya, T and Ashimori, A and Higashijima, F and Yoshimoto, T and Morita, T and Murai, T and Kirihara-Kojima, S and Kimura, K},
title = {A novel prohibitin inhibitor acts as a dual inhibitor of angiogenesis and fibrosis.},
journal = {Biochemical and biophysical research communications},
volume = {805},
number = {},
pages = {153386},
doi = {10.1016/j.bbrc.2026.153386},
pmid = {41633199},
issn = {1090-2104},
abstract = {We previously showed that the benzoylphenylurea derivative BPU17 inhibits epithelial-mesenchymal transition and acts as an antifibrotic agent. This compound acts as a prohibitin (PHB) inhibitor by directly binding to PHB1. This binding disrupts the interaction between PHB1 and PHB2, leading to mild mitochondrial dysfunction. Here, we investigated the effect of BPU17 on angiogenesis using primary cultures of human vascular and microvascular endothelial cells, as well as a mouse model of choroidal neovascularization (CNV). A series of studies has shown that BPU17 inhibits angiogenesis both in vitro and in vivo. The molecular mechanism is that BPU17 inhibits serum response factor (SRF)/CArG box-mediated transcription by repressing the expression of SRF and its cofactor myocardin-related transcription factors (MRTF-A and -B [MRTF]). This defect causes the downregulation of adaptor and cell adhesion molecules such as vinculin and integrins, leading to the inhibition of angiogenesis. This inhibitory effect is closely associated with mild mitochondrial dysfunction, and siRNA-mediated knockdown of PHB1 similarly inhibits angiogenesis. Given that age-related inflammatory responses and subsequent choroidal neovascularization (CNV) contribute to the development of neovascular age-related macular degeneration (nAMD), this novel PHB inhibitor holds promise as a treatment for nAMD through its dual inhibitory effects on angiogenesis and fibrosis.},
}

@article {pmid41632743,
year = {2026},
author = {Belloni Baroni, L and Toto, L and Formenti, F and Passamonti, M and Quarta, A and Ruggeri, ML and Aloia, R and Di Nicola, M and Mastropasqua, R},
title = {Long term follow up of faricimab intravitreal injections in naïve neovascular age related macular degeneration.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1-15},
doi = {10.1159/000550307},
pmid = {41632743},
issn = {1423-0259},
abstract = {INTRODUCTION: The aim of the study was to evaluate functional and anatomical changes at 44 weeks follow up in patients with naïve neovascular age-related macular degeneration (nAMD) treated with faricimab intravitreal injections (IVIs).

METHODS: Fifty-four eyes of 54 patients with naïve active macular neovascularization and nAMD were enrolled at the Ophthalmology Clinic of University "G. d'Annunzio", Chieti-Pescara, Italy. All patients were scheduled for faricimab IVI. Each patient underwent complete ophthalmic examination including best-corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) charts and optical coherence tomography (OCT). All measurements were evaluated at baseline, at week 20 and then according to fixed retreatment interval up to week 44. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) were also performed at baseline. Main outcome measures were changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), intraretinal fluid (IRF) presence, subfoveal subretinal fluid (SSRF) presence and thickness, pigment epithelial detachments (PEDs) presence and maximum height (PED-MH).

RESULTS: BCVA improved and CMT reduced significantly from baseline to week 44 (p=0.002 and p=0.020, respectively) in the overall sample with a higher significant improvement from baseline to week 20 (p<0.001 for both parameters) and no additional significant improvement from week 20 to week 44 in the overall sample (p=0.348 and p=0.146, respectively). At week 20, 72.3% of patients were in the Q12/ Q16 interval. Patients in q8 interval showed significant improvement of BCVA (p < 0.001) and significant reduction of CMT (p=0.008) from baseline to week 44 respectively. PED-MH as well showed a significant reduction from baseline to week 44 (p <0.001). Patients in Q12 interval showed significant improvement of BCVA (p=0.030) and significant reduction of CMT, SFCT and PED-MH from baseline to week 36 (p<0.001). Patients in Q16 interval show significant reduction of BCVA during follow up (p=0.026). CMT, SFCT and PED-MH were significantly reduced from baseline to week 44 (p < 0.001).

CONCLUSION: Faricimab showed efficacy in the treatment of naïve nAMD patients with an improvement of many anatomical and functional parameters at 44 weeks allowing to maintain a treatment regimen for most patients equal to or greater than 12 weeks.},
}

@article {pmid41632222,
year = {2026},
author = {Kim, JY and Lee, J and Oh, SB and Kim, C and Park, YH},
title = {α-Crystallins and vascular endothelial growth factor in aqueous humor of patients with neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41632222},
issn = {1613-2246},
support = {ZC23TISI0770//Seoul St. Mary's Hospital, Catholic University of Korea/ ; RS-2023-00253065//National Research Foundation/ ; },
abstract = {PURPOSE: This study investigated aqueous humor (AH) levels of α-crystallins and vascular endothelial growth factor (VEGF) in patients with neovascular age-related macular degeneration (nAMD).

STUDY DESIGN: Prospective study.

METHODS: AH samples were collected from treatment-naïve phakic nAMD patients before the first and third anti-VEGF injections and from cataract patients without retinal disease as controls. αB-crystallin, αA-crystallin, and VEGF levels were quantified using enzyme-linked immunosorbent assay. Patients were classified as good responders (achieved remission) or poor responders (persistent intraretinal or subretinal fluid) according to response after three consecutive monthly anti-VEGF injections.

RESULTS: A total of 28 eyes from 24 nAMD patients and 27 eyes from 23 controls were analyzed. nAMD showed higher αB-crystallin and VEGF, but similar αA-crystallin levels versus controls (P < 0.001, P = 0.002, and P = 0.721, respectively). In nAMD eyes, after two anti-VEGF injections, αB-crystallin and αA-crystallin remained unchanged, whereas VEGF decreased (P = 0.057, P = 0.182, and P = 0.017, respectively). Among nAMD eyes, 20 eyes from 18 patients were good responders and 8 from 6 were poor responders. Good responders demonstrated reductions in αB-crystallin and VEGF (P = 0.016 and P = 0.002, respectively), whereas poor responders showed no significant changes (P = 0.249 and P = 0.075, respectively). In untreated nAMD eyes, αB-crystallin and VEGF levels showed a positive correlation (P = 0.010).

CONCLUSION: In nAMD, AH αB-crystallin levels were elevated compared with controls. Among good responders to anti-VEGF therapy, αB-crystallin levels decreased. Moreover, αB-crystallin levels showed a positive correlation with VEGF.},
}

@article {pmid41631247,
year = {2026},
author = {Hsiao, YJ and Li, H and Xue, CC and Chong, CCY and Zhu, E and Yuan, Q and Yu, M and Cheung, CMG and Fan, Q and Sabanayagam, C and Tham, YC and Cheng, CY},
title = {Chronic Kidney Disease as a Risk Factor for Age-Related Macular Degeneration: A Prospective Cohort and Mendelian Randomization Analyses.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {101036},
pmid = {41631247},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate shared genetic influences and investigate the association of chronic kidney disease (CKD) with the risk for advanced age-related macular degeneration (AMD).

DESIGN: Prospective cohort study and 2-sample Mendelian randomization (MR) analyses.

PARTICIPANTS: Data from 430 016 participants in the UK Biobank cohort and summary statistics from the largest publicly available genome-wide association studies on estimated glomerular filtration rate (eGFR) (n = 1 004 040) and advanced AMD (n = 33 976; 16 144 cases) were analyzed.

METHODS: Cox regression models were used to assess the association between CKD and incident AMD, adjusting for demographic, lifestyle, and clinical covariates. For MR analyses, we used the random-effects inverse-variance weighted model as the primary model, supported by 5 additional MR models for sensitivity analyses. A causal relationship was considered significant if P < 0.05 in the primary model and in ≥2 sensitivity models, with all MR models showing a consistent effect direction. Colocalization analysis was performed to further identify shared genetic loci linking CKD and AMD.

MAIN OUTCOME MEASURES: Causal associations between eGFR and advanced AMD.

RESULTS: In the UK Biobank, baseline CKD was significantly associated with an increased risk of incident AMD (hazard ratio, 1.12; 95% confidence interval [CI], 1.01-1.25; P = 0.035) over a 10-year follow-up. Mendelian randomization analyses also demonstrated causality between lower eGFR and higher risk of advanced AMD (odds ratio, 2.03; 95% CI, 1.01-4.08; P = 0.048). Colocalization analysis indicated that the apolipoprotein E gene may contribute to this causality (rs56131196; colocalization posterior probability = 1.00, P = 2.29 x 10[-33] for AMD; P = 2.29 x 10[-13] for eGFR).

CONCLUSIONS: Both prospective cohort and MR analyses support causality between CKD and AMD, highlighting the need for AMD screening among patients with CKD.

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

@article {pmid41630283,
year = {2026},
author = {Chen, J and Chen, T and Zhao, C and Bao, Z and Liu, H},
title = {Mendelian randomization study of causality between 35 blood and urine biomarkers and age-related eye diseases.},
journal = {Medicine},
volume = {105},
number = {5},
pages = {e47286},
doi = {10.1097/MD.0000000000047286},
pmid = {41630283},
issn = {1536-5964},
mesh = {Humans ; Mendelian Randomization Analysis ; *Biomarkers/urine/blood ; Macular Degeneration/urine/genetics/blood ; Cataract/urine/genetics/blood ; *Eye Diseases/urine/blood/genetics ; Glaucoma/urine/genetics/blood ; Diabetic Retinopathy/urine/genetics/blood ; Causality ; },
abstract = {Age-related eye diseases (AREDs) are a group of age-related visual degenerative diseases characterized by insidious and gradual onset. Identification of biomarkers associated with the early stage of AREDs is particularly important to delay its progression. This study aimed to evaluate the causal relationship between 35 blood and urine biomarkers and AREDs, thereby providing new insights into disease mechanisms and potential therapeutic targets. Two-sample Mendelian randomization (MR) was used to clarify the causal relationship between blood and urine biomarkers and AREDs. We classified AREDs into 4 types: age-related cataract (SC), age-related macular degeneration, glaucoma, and diabetic retinopathy. Inverse variance weighting method was used as the main analysis method, Cochran Q test, MR-Egger intercept, and leave-one-out test were used to investigate whether there was heterogeneity and pleiotropy of MR results. And the results were corrected by false discovery rate. Through MR analysis, this study provides the first systematic genetic evidence regarding the associations between blood and urine biomarkers and 4 AREDs. Specifically, our findings suggest a causal effect of 1 biomarker on SC, support causal roles of 3 biomarkers in age-related macular degeneration, and indicate causal relationships for 3 biomarkers with diabetic retinopathy. The reliability of these results was bolstered by a series of sensitivity analyses. This study strengthened the link between specific blood and urine biomarkers and the risk of AREDs. It has enhanced our understanding of the pathogenesis of AREDs and may guide the development of targeted prevention, diagnosis, and treatment strategies.},
}

Humans
Mendelian Randomization Analysis
*Biomarkers/urine/blood
Macular Degeneration/urine/genetics/blood
Cataract/urine/genetics/blood
*Eye Diseases/urine/blood/genetics
Glaucoma/urine/genetics/blood
Diabetic Retinopathy/urine/genetics/blood
Causality

@article {pmid41630010,
year = {2026},
author = {Cassavia Junior, ASF and Bellanda, V and Audi, LO and Barbosa, GCS and Caravelas, RAM and Volpe, GJ and Moreira, HT and Schmidt, A and Jorge, R},
title = {Assessing the prevalence of extensive macular atrophy with pseudodrusen-like appearance in patients with rheumatic fever-associated valvular heart disease: a cross-sectional study.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00805-6},
pmid = {41630010},
issn = {2056-9920},
}

@article {pmid41629572,
year = {2026},
author = {Kindo, H and Hosokawa, MM and Ouchi, C and Matoba, R and Morita, T and Hayashi, J and Morizane, Y},
title = {Real-world six-month outcomes after switching from aflibercept 2 mg to aflibercept 8 mg for neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41629572},
issn = {1613-2246},
abstract = {PURPOSE: To investigate 6-month outcomes in eyes with neovascular age-related macular degeneration (nAMD) switched from intravitreal aflibercept 2 mg to intravitreal aflibercept 8 mg.

STUDY DESIGN: Retrospective observational study.

METHODS: We reviewed records of consecutive nAMD eyes switched from aflibercept 2 mg to 8 mg. In eyes continuing aflibercept 8 mg, best-corrected visual acuity (BCVA), treatment intervals, and anatomical/exudative parameters were evaluated at 6 months. In eyes that could not continue, reasons for discontinuation were examined.

RESULTS: Forty-four eyes from 44 patients were included. At 6 months, 35 eyes (79.5%) continued and 9 (20.5%) discontinued aflibercept 8 mg. Discontinuing eyes had significantly shorter pre-switch treatment intervals and more frequent prior therapies than continuing eyes. In the continuation group, BCVA remained stable (median 0.05 to 0.00 logMAR, P = 0.351), while the treatment interval was significantly extended (median 7.0 to 9.0 weeks, P < 0.001). Central retinal thickness and pigment epithelial detachment height decreased significantly (P = 0.035 and P = 0.021, respectively). The proportion of eyes with subretinal fluid significantly decreased from 74.3 to 37.1% (P = 0.003). Of the discontinuations, 4 were due to worsening exudation and 5 to inability to extend to ≥8 weeks as required by labeling. No intraocular inflammation or serious adverse events occurred.

CONCLUSIONS: Switching to aflibercept 8 mg achieved anatomical improvements and longer treatment intervals in ~80% of nAMD cases, suggesting it may be a useful alternative to aflibercept 2 mg. However, continuation may be difficult in refractory cases requiring frequent injections before switching.},
}

@article {pmid41629364,
year = {2026},
author = {Spörri, L and Studer, JM and Kreuzer, M and Rotzetter, J and Schärer, D and Largiadèr, CR and Jaggi, D and Zinkernagel, MS and Zysset-Burri, DC},
title = {Linking the microbiome to the complement system in geographic atrophy.},
journal = {NPJ genomic medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41525-026-00550-7},
pmid = {41629364},
issn = {2056-7944},
support = {CF10000044-EPFL SCR0237812//Foundation Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique Fédérale de Lausanne), Lausanne, Switzerland/ ; CF10000044-EPFL SCR0237812//Foundation Bertarelli Catalyst Fund, EPFL (Ecole Polytechnique Fédérale de Lausanne), Lausanne, Switzerland/ ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in the aged population with the late stage geographic atrophy (GA). Risk factors for AMD include age, genetic variants in the complement system, nutritional factors, and alterations in the gut microbiome (GM). To identify taxonomic and functional differences in the microbiome associated to disease pathophysiology and genetic risk factors, this study investigated the GM and the ocular surface microbiome (OSM) of GA patients compared to healthy controls by whole-metagenome shotgun sequencing. 16 AMD-associated SNPs were genotyped from blood samples using TaqMan assays and Sanger sequencing. While GA patients showed differences in the GM, and altered metabolic pathways including inosine 5'-phosphate degradation, NAD salvage, and ketogenesis, no alterations in the OSM were found. Genetic analysis associated SNP rs1061170 in the complement factor H gene with GA. These findings suggest that microbial alterations may contribute to GA through inflammation and oxidative stress.Registry: ClinicalTrials.gov, NCT02438111, Registration date: 28 April 2015, and NCT04658238, Registration date: 01 December 2020.},
}

@article {pmid41627545,
year = {2026},
author = {Cheng, X and Zeng, X and Liu, S and Liu, C and Liu, Y and Xu, G},
title = {Shared diagnostic biomarkers and diagnostic models of age-related macular degeneration and systemic lupus erythematosus.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {95},
pmid = {41627545},
issn = {1573-2630},
support = {U2267220//Yulong Liu/ ; },
mesh = {Humans ; *Lupus Erythematosus, Systemic/diagnosis/genetics/metabolism ; *Macular Degeneration/diagnosis/genetics/metabolism ; *Biomarkers/metabolism ; Gene Expression Profiling ; Mendelian Randomization Analysis ; },
abstract = {PURPOSE: This study aimed to investigate the potential link between age-related macular degeneration (AMD) and systemic lupus erythematosus (SLE), exploring whether AMD may share underlying autoimmune mechanisms with SLE. The objective was to identify shared core genes and potential diagnostic biomarkers for both diseases.

METHODS: We utilized GEO datasets to develop diagnostic models and performed differential gene expression analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning techniques-LASSO regression, random forest (RF), and support vector machine recursive feature elimination (SVM-RFE)-to identify common key genes between AMD and SLE. Mendelian randomization analysis was conducted to validate the potential causal relationship between AMD and the identified essential genes. Single-cell RNA sequencing data were analyzed to explore the expression patterns of shared biomarkers at the cellular level. The expression level of the identified biomarker was validated using reverse transcription quantitative polymerase chain reaction and Western blotting.

RESULTS: Several shared core genes were identified as associated with both AMD and SLE. The Mendelian randomization study confirmed a potential correlation between AMD and these essential genes. Single-cell transcriptomic analysis revealed distinct expression profiles of these markers across relevant cell types, supporting their role in disease pathology.

CONCLUSION: Our findings suggest that AMD and SLE share key genetic features, supporting the hypothesis that AMD may have an autoimmune component. These shared genes hold promise as potential therapeutic targets and diagnostic biomarkers for both diseases.},
}

Humans
*Lupus Erythematosus, Systemic/diagnosis/genetics/metabolism
*Macular Degeneration/diagnosis/genetics/metabolism
*Biomarkers/metabolism
Gene Expression Profiling
Mendelian Randomization Analysis

@article {pmid41627332,
year = {2026},
author = {Kado Abdalkader, R and Kawakami, S and Takashima, Y and Fujita, T},
title = {Development of a 3D-printed microfluidic chip for retinal organoid-endothelial co-culture.},
journal = {Lab on a chip},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5lc00939a},
pmid = {41627332},
issn = {1473-0189},
abstract = {Pathological angiogenesis, such as that observed in wet age-related macular degeneration (AMD), is difficult to reproduce in vitro using human-relevant models. Although organ-on-chip (OoC) systems incorporating retinal pigment epithelium (RPE) and endothelial barriers have been reported, models integrating human retinal organoids with vascular networks remain limited. Here, we present a fully 3D-printed microfluidic platform for co-culture of human induced pluripotent stem cell (hiPSC)-derived retinal organoids containing intrinsic RPE regions with endothelial cells. The device, fabricated from flexible thermoplastic polyurethane (TPU) on a transparent polyvinyl chloride (PVC) substrate, supports three-dimensional co-culture within a fibrin-Matrigel matrix. In this system, endothelial cells formed organized vascular networks that localized around RPE-associated regions of retinal organoids without direct tissue invasion. Organoid-endothelial co-culture resulted in increased VEGF secretion, while exogenous VEGF further enhanced endothelial localization near RPE regions without affecting organoid growth. Functional assays using fluorescent dextran and rhodamine-labeled liposomal nanoparticles demonstrated spatially restricted and time-dependent transport along vascularized regions adjacent to the organoid interface. This retinal organoid-on-chip provides a simple and robust in vitro platform for studying retinal-vascular interactions and vascular-mediated transport processes.},
}

@article {pmid41626488,
year = {2026},
author = {Wang, Y and Chen, S and Cao, Y and Wen, X and Fu, C and Liang, J and Luo, Q and Liu, Q},
title = {Molecular Dynamics and Experimental Validation of Natural Products from Chuanxiong Rhizoma as VEGFR2 Inhibitors for nAMD Therapy.},
journal = {ACS omega},
volume = {11},
number = {3},
pages = {3949-3964},
pmid = {41626488},
issn = {2470-1343},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness among the elderly worldwide. Neovascular AMD (nAMD) is a significant subtype of AMD, responsible for the blindness of over 90% of patients with AMD. The hallmark of nAMD is choroidal angiogenesis dysregulation, a condition that can result in severe inflammation, leakage, and bleeding, ultimately leading to a precipitous decline in visual acuity. Inhibition of the vascular endothelial growth factor (VEGF) pathway has been proven to be an effective therapeutic strategy for this disease. Intraocular injection of anti-VEGF macromolecule drugs is a clinical therapy for this disease, but it has shortcomings, such as severe side effects, high cost, long treatment cycle, and complex administration methods. Consequently, the identification of novel small-molecule drugs and the development of innovative delivery mechanisms are of paramount importance for the treatment of this condition. Chuanxiong Rhizoma (CX), a type of traditional Chinese medicine (TCM), has been employed in the treatment of vascular-related diseases. Contemporary pharmacological research has demonstrated that CX contains a substantial quantity of natural compounds that exhibit anti-VEGF activity. In this study, we employed molecular simulation docking and molecular dynamics (MD) to examine the anti-VEGFR2 effects of 10 natural compounds derived from CX. Sorafenib was selected as the reference ligand, which is a marketed VEGFR2 inhibitor for cancer treatment. As a DFG-out inhibitor, sorafenib stabilizes the inactive conformation of the kinase by binding to an allosteric site near the ATP-binding pocket. In our research, natural products exhibiting a strong binding affinity were identified using computer-simulated docking technology and detailed binding sites were predicted. The findings of the research indicate that apigenin exhibits the strongest affinity for the VEGFR2 receptor with the formation of three hydrogen bonds. The molecular docking results indicate that the CYS919 and ASP1046 amino acid residues of VEGFR2 are the primary groups that form hydrogen bonds with the ligands. Furthermore, the AutoQSAR module of Schrödinger Suite predicted apigenin to have the highest predicted pIC50 value among the ten candidate compounds, suggesting its potential for significant VEGFR2 inhibitory activity. A subsequent MD simulation revealed that the binding of apigenin to the protein was more stable, and the conformation was stronger. According to the ADMET prediction results, apigenin is characterized by low toxicity. To ascertain the capacity of apigenin to impede the proliferation of choroidal angiogenesis, the choroid sprouting assay was utilized as a methodological framework. An in vitro experiment demonstrated that apigenin can significantly inhibit the growth of choroidal vessels in a dose-dependent manner. The present study was conducted with the objective of assessing the potential of natural products in the treatment of nAMD. In addition, the study offered valuable insights for the development of new natural agents.},
}

@article {pmid41626425,
year = {2026},
author = {Chen, ZJ and Yu, J and Ho, M and Ng, DSC and Brelen, ME and Young, AL and Yam, JCS and Tham, CC and Pang, CP and Chen, LJ},
title = {The CFH-CFHR5 Locus in Wet Age-Related Macular Degeneration, Polypoidal Choroidal Vasculopathy, and Central Serous Chorioretinopathy.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {101043},
pmid = {41626425},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the effects of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement factor H-complement factor H related 5 (CFH-CFHR5) locus on neovascular age-related macular degeneration (nAMD), polypoidal choroidal vasculopathy (PCV), and chronic central serous chorioretinopathy (cCSCR) in Chinese patients.

DESIGN: Case-control genetic association study.

PARTICIPANTS: A total of 846 patients (341 nAMD, 288 PCV, and 217 cCSCR including 43 with secondary macular neovascularization [MNV]) and 632 healthy Chinese controls.

METHODS: A total of 17 candidate SNPs were initially selected from the CFH-CFHR5 region; after excluding 5 SNPs that deviated from Hardy-Weinberg equilibrium, 12 SNPs were retained for the final analysis. Association analyses included logistic regression adjusted for age and sex and haplotype-based analysis using Haploview. Study-wide significance threshold was set at P < 0.0042 for allelic tests (Bonferroni-corrected for 12 SNPs) and at P < 0.05 for haplotype tests (adjusted using 10 000 permutations).

MAIN OUTCOME MEASURES: Associations between individual SNPs and haplotypes in the CFH-CFHR5 locus with nAMD, PCV, and cCSCR (with or without MNV), respectively.

RESULTS: The tagging SNP, rs12144939, for the CFHR3/1 deletion was significantly associated with nAMD (odds ratio [OR] = 0.37, P = 0.0031). Notably, we identified 3 candidate variants showing novel associations with PCV, including rs12144939 (OR = 0.29, P = 6.29 × 10[-4]), rs423641 in CFHR1 (OR = 0.74, P = 0.0038), and rs10922152 in CFHR5 (OR = 1.55, P = 0.0031). No SNP in this locus was associated with cCSCR without MNV, whereas CFH rs529825 was nominally associated with cCSCR with MNV (OR = 0.47, P = 0.0047). Similar patterns of haplotype associations were observed across the 3 maculopathies. Notably, the haplotype A-T-C-G spanning CFHR4, CFHR2, and CFHR5 (OR = 1.81, permutation P = 0.0099) and haplotype G-A-G within CFHR5 (OR = 1.56, permutation P = 0.025) were specifically associated with PCV.

CONCLUSIONS: This study validates the association of the CFHR3/1 deletion (tagged by rs12144939) with nAMD. Furthermore, we reveal a novel genetic architecture for PCV within the CFH-CFHR5 locus, characterized by associations at rs12144939, rs423641 (CFHR1), and rs10922152 (CFHR5), as well as risk haplotypes unique to PCV. These findings underscore the critical role of CFH-related genes in PCV and provide new insights into its genetic mechanisms.

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

@article {pmid41626424,
year = {2026},
author = {Mukherjee, S and Wu, D and Emde, LV and Vance, E and Ji, M and Emamverdi, M and De Silva, T and Thavikulwat, AT and Kalpathy-Cramer, J and Domalpally, A and Cukras, CA and Keenan, TDL},
title = {ReticularNet: Automated Pixel-Level Segmentation of Reticular Pseudodrusen on Near-Infrared Reflectance Images by Deep Learning.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {101038},
pmid = {41626424},
issn = {2666-9145},
abstract = {OBJECTIVE: Reticular pseudodrusen (RPD) represent an important biomarker in age-related macular degeneration (AMD) but are difficult to grade and often assessed only for presence or absence, without quantitative or spatial analysis of RPD burden. The objective was to develop and validate a deep learning model for pixel-level RPD grading on near-infrared reflectance (NIR) images, which are commonly acquired in clinical practice and the most accurate en face detection modality.

DESIGN: Deep learning model development study.

PARTICIPANTS: Five hundred eight images of 117 eyes (70 participants) with or without RPD, over a wide range of AMD severities.

METHODS: The ground truth grading pipeline comprised reading center multimodal grading for RPD presence and NIR annotation with RPD contours, followed by pixel-level NIR annotation of all individual RPD lesions. The data set was split 80:20 into training and test sets. A DeepLabv3-ResNet-18 segmentation deep learning model ("ReticularNet") was trained to perform pixel-level grading of RPD on NIR images. Its performance was compared with that of 4 ophthalmologists.

MAIN OUTCOME MEASURES: Dice similarity coefficient (DSC); intraclass correlation coefficient (ICC) for RPD lesion number, pixel area, and contour area.

RESULTS: For pixel-level grading, ReticularNet achieved a mean DSC of 0.36 (standard deviation 0.16). This was significantly higher than the mean DSC of each ophthalmologist (0.03, 0.13, 0.19, and 0.23; P ≤ 0.02 for each) and of all ophthalmologists together (P < 0.0001). ReticularNet had ICCs of 0.44 (lesion number), 0.56 (pixel area), and 0.61 (contour area), with no significant underestimation or overestimation (P ≥ 0.24). These values were numerically higher than the ICCs of each ophthalmologist, who had ICC ranges of -0.08 to 0.23, -0.05 to 0.40, and -0.09 to 0.58, respectively, and significant underestimation in almost all cases. For all 3 parameters, ReticularNet's ICC was significantly higher than that of all specialists considered together (P ≤ 0.02).

CONCLUSIONS: ReticularNet achieved automated pixel-level grading of RPD on NIR images. Its grading was superior to that of 4 ophthalmologists, across a variety of metrics. We are making the code/models available for research use. Improved access to quantitative and spatial RPD grading should lead to improved understanding of these lesions as important biomarkers of retinal disease.

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

@article {pmid41624137,
year = {2025},
author = {Rusciano, D and Bagnoli, P},
title = {The controversial role of nutraceuticals vs. drugs in proliferative retinopathies.},
journal = {Frontiers in neuroscience},
volume = {19},
number = {},
pages = {1727089},
pmid = {41624137},
issn = {1662-4548},
abstract = {Neovascular eye diseases, notably age-related macular degeneration and diabetic retinopathy, remain major causes of vision loss despite advances in pharmacological management. The proliferation of abnormal retinal blood vessels leads to the loss of retinal cells and progressive visual dysfunction. Anti-VEGF therapies have revolutionized treatment; however, their efficacy is incomplete, they require repeated administration, and resistance or suboptimal responses are not uncommon. These limitations have stimulated interest in additional therapeutic approaches, both inspired by preclinical research and aimed at improving the management of systemic conditions that contribute to neovascular pathologies. Beyond conventional pharmacology, nutraceuticals have attracted attention for their proposed mechanisms-enhancement of antioxidant defenses, modulation of inflammatory cascades, and potential interference with angiogenic signaling-which provide a molecular rationale for their application in ocular disease. This review critically examines the dual landscape of current pharmacological strategies and nutraceutical approaches, analyzing how the latter might enhance retinal resilience and vascular stability in the early stages of disease. The novelty of this work lies in juxtaposing the mechanistic underpinnings of nutraceuticals with the clinical shortcomings of anti-VEGF therapy, thereby identifying opportunities for integrative therapeutic perspectives. Nevertheless, nutraceuticals cannot replace pharmacological treatment in advanced disease; rather, they may offer incremental benefits in early-stage or high-risk patients, contingent upon timely preventive diagnosis. Until more robust clinical evidence and regulatory oversight are established, nutraceuticals should be regarded as adjunctive components within personalized care models-supporting, but not substituting for, established pharmacological interventions.},
}

@article {pmid41622479,
year = {2026},
author = {Løkken, JFT and Moe, MC and Sæther, EM and Jørstad, ØK},
title = {Beyond drug price: A comparison of overall costs of anti-vascular endothelial growth factor therapy alternatives for neovascular age-related macular degeneration in Norway.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70069},
pmid = {41622479},
issn = {1755-3768},
support = {//Bayer Norway/ ; },
abstract = {PURPOSE: Norwegian guidelines designate off-label Avastin as the first-line intravitreal therapy for neovascular age-related macular degeneration (nAMD) because of its well-documented clinical efficacy and low price. However, this overlooks non-drug costs, which increase with injection frequency. We evaluated whether newer, longer-acting agents offer greater long-term cost-efficiency by reducing total costs despite higher drug prices in a Norwegian setting.

METHODS: We developed a 2-year cost-minimization model that included pharmaceutical, consultation and administrative and patient-related costs in Norway; the pharmaceutical cost component incorporated the routine practice of splitting vials into prefilled syringes in hospital pharmacies. The model compared four nAMD monotherapies, Avastin, Eylea 2 mg, Eylea 8 mg and Vabysmo, as well as the common practice of switching treatment-resistant patients from Avastin to Eylea 2 mg. We derived injection frequencies from clinical trials (for monotherapies) or observational data (for switching) and conducted one-way sensitivity analyses to identify key cost drivers.

RESULTS: Over 2 years, the switching regimen had the highest per-patient cost (146 722 NOK), followed by Eylea 2 mg (100 481 NOK), Vabysmo (93 207 NOK), Avastin (86 262 NOK) and Eylea 8 mg (68 738 NOK). Avastin had the lowest drug cost, but its high injection frequency increased non-drug costs. Sensitivity analyses showed that injection frequency strongly influenced total costs for high-priced drugs, while patient time had a substantial impact for Avastin.

CONCLUSION: In our model, longer-acting agents reduced injection frequency and decreased overall treatment costs. These findings suggest that adopting longer-acting monotherapy could improve cost-efficiency in long-term nAMD management in Norway.},
}

@article {pmid41622390,
year = {2026},
author = {Chen, X and Shi, W and Zhu, Y and Li, K and Xia, Y and Wu, H and Hu, T and Qin, C and Wei, W},
title = {PF protects retinal pigment epithelial cells from oxidative injury by enhancing mitophagy through a CUL3-dependent AMPK/ULK1 pathway.},
journal = {Archives of pharmacal research},
volume = {},
number = {},
pages = {},
pmid = {41622390},
issn = {1976-3786},
support = {QN202414//Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; GSPYY2023009//Jiangsu Provincial Administration of Traditional Chinese Medicine/ ; },
abstract = {Mitophagy dysfunction is a critical contributor to retinal pigment epithelial (RPE) cell damage during the progression of retinal degenerative diseases, including age-related macular degeneration (AMD). In this study, we investigated the effects of paeoniflorin (PF) on mitophagy in RPE cells, with a particular focus on the CUL3/LKB1/AMPK/ULK1 signaling pathway. ARPE-19 cells were treated with different concentrations of PF to evaluate cytotoxicity, and its protective effects were further examined in H2O2-induced oxidative stress models in vitro and in sodium iodate (NaIO3)-induced RPE injury models in vivo. Protein levels of CUL3, apoptosis-related factors, mitophagy markers, and components of the LKB1/AMPK/ULK1 pathway were assessed by western blotting, and mitophagy was visualized using MitoTracker labeling. Cycloheximide (CHX) and coimmunoprecipitation (Co-IP) assays were performed to analyze the interaction between CUL3 and LKB1. PF treatment enhanced mitophagy in H2O2-stimulated ARPE-19 cells, whereas Parkin knockdown markedly attenuated this effect. In oxidatively damaged cells, PF promoted AMPK and ULK1 phosphorylation, increased mitophagy-associated protein expression, and alleviated mitochondrial dysfunction; these protective effects were abolished by pharmacological inhibition of AMPK or ULK1. In addition, CUL3 overexpression significantly attenuated PF-induced mitophagy activation and reduced PF-associated phosphorylation of LKB1, AMPK, and ULK1. Mechanistically, PF downregulated CUL3 expression, while CUL3 promoted the ubiquitination and degradation of LKB1. Silencing CUL3 induced mitophagy in H2O2-treated cells, whereas concurrent knockdown of CUL3 and LKB1 abolished this effect. In vivo, PF mitigated RPE cell loss, enhanced mitophagy, and activated the CUL3/LKB1/AMPK/ULK1 signaling pathway in the retinal tissues of NaIO3-induced mice. Collectively, these findings indicate that PF protects against RPE injury in an NaIO3-induced AMD-like model by downregulating CUL3 expression and activating LKB1/AMPK/ULK1-mediated mitophagy.},
}

@article {pmid41622023,
year = {2026},
author = {Hart, KM and Ayton, LN and Wu, Z},
title = {Developing age-related macular degeneration recommendations for clinical optometrists via a modified Delphi study.},
journal = {Clinical & experimental optometry},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/08164622.2025.2610977},
pmid = {41622023},
issn = {1444-0938},
abstract = {CLINICAL RELEVANCE: Clear, evidence-based guidelines support optometrists in diagnosing and managing age-related macular degeneration, a leading cause of vision loss in older adults. This condition is an increasing focus of clinical care due to expanding treatment options and evolving imaging technologies.

BACKGROUND: Clinical practice guidelines support consistent, evidence-based care in optometry and play a critical role in guiding the diagnosis and management of chronic eye diseases. This paper discusses the methodological approach used to develop age-related macular degeneration guidelines, emphasising the modified Delphi approach used to refine and formally establish recommendations.

METHODS: Recommendations were developed from a literature review and draft guideline. An expert working group of optometrists (n = 9) participated in a three-round Delphi process, rating their agreement with the draft recommendations using a 6-point Likert scale across two survey rounds, followed by a virtual meeting to discuss and re-vote on unclear or contentious items. Quantitative and qualitative measures during the first two rounds of the Delphi survey guided recommendation refinement and inclusion for discussion in round 3. Consensus for inclusion was defined as a mean score ≥5 and ≥80% agreement.

RESULTS: Out of 37 initial recommendations, 25 (68%) were accepted and included in the final guideline. Consensus was achieved for recommendations concerning clinical classification, assessment and management strategies. Round 3 discussions helped resolve uncertainties and refine recommendations wording, particularly regarding nutritional supplements and clinical biomarkers for progression. Adoption of the Delphi approach demonstrated the value of both quantitative and qualitative feedback.

CONCLUSION: The feasibility and value of using a modified Delphi method to develop optometric clinical practice guidelines is demonstrated. The process supported the inclusion or exclusion of recommendations in a systematic way with the final guideline offering contemporary, practice-relevant guidance for the diagnosis and management of age-related macular degeneration.},
}

@article {pmid41621806,
year = {2026},
author = {Xiao, JF and Hyman, MJ and Moir, J and Yehia, M and Hariprasad, S and Flores, A and Skondra, D},
title = {Association of metformin use and new-onset ICD coding of neovascular age-related macular degeneration.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.01.019},
pmid = {41621806},
issn = {2468-6530},
abstract = {PURPOSE: To investigate whether metformin use is associated with decreased odds of new-onset International Classification of Disease (ICD) coding of neovascular age-related macular degeneration (nAMD).

DESIGN: Case-control study.

PARTICIPANTS: 22,205 cases with new-onset ICD coding of nAMD and 22,126 matched controls without AMD were identified in the Merative™ MarketScan® Research Databases between 2008 and 2017. A subgroup of patients diagnosed with diabetes included 6,664 cases and 5,513 controls.

METHODS: Cases with new-onset ICD coding of nAMD were propensity score matched to controls without AMD. Multivariable conditional logistic regression analyzed the association between new-onset ICD coding of nAMD and metformin use controlling for (1) AMD risk factors, including diabetes, diabetic retinopathy, hyperlipidemia, obesity, and smoking, (2) exposures to other antidiabetic medications, including insulin, sulfonylureas, glitazones, meglitinides, other diabetic medications, and statins, and (3) the number of antidiabetic medications.

MAIN OUTCOME MEASURES: Adjusted odds ratios of new-onset ICD coding of nAMD for any metformin use and cumulative two-year metformin dose in grams (g).

RESULTS: Any metformin use was associated with decreased adjusted odds of new-onset nAMD (aOR 0.84, 95% CI 0.74-0.95). In an exploratory dosing analysis, associations across cumulative-dose categories were heterogeneous, with the largest magnitude in the mid-dose range (between 271 and 600 g; aOR 0.73, 95% CI 0.63-0.85); because adherence cannot be verified from claims, dose-response findings are interpreted as hypothesis-generating. These associations persisted among diabetic patients (Any metformin use: aOR 0.83, 95% CI 0.72-0.94; 271 to 600 g: aOR 0.72, 95% CI 0.61-0.85; >1080 g: aOR 0.85, 95% CI 0.72-0.999). Any metformin use in diabetic patients without retinopathy was associated with decreased odds of new-onset ICD nAMD (aOR 0.85, 95% CI 0.78-0.93); however, this association was absent in diabetic patients with retinopathy.

CONCLUSIONS: In this claims-based analysis, metformin use was associated with lower odds of incident ICD-coded nAMD, and an exploratory dosing analysis suggests a low to moderate cumulative dose may be associated with the greatest decrease. These associations persisted among diabetic patients without retinopathy. Causal inference is limited by the observational design, potential diagnostic misclassification, imperfect exposure measurement, and residual confounding. Replication with validated case definitions, active-comparator new-user designs, and adjudicated outcomes is warranted.},
}

@article {pmid41621805,
year = {2026},
author = {Sarraf, D and Corvi, F and Rosenfeld, PJ and Ach, T and Blodi, B and Bottoni, F and Cozzi, M and Chakravarthy, U and Chew, EY and Csaky, K and Cukras, C and Curcio, CA and Ferris, FL and Freund, KB and Grunwald, J and Guymer, RH and Holz, FG and Jaffe, GJ and Liakopoulos, S and Lim, TH and Monés, JM and Owsley, C and Pagliarini, S and Pauleikhoff, D and Schmitz-Valckenberg, S and Spaide, RF and Sparrow, J and Tadayoni, R and Tufail, A and Viola, F and Fraser, S and Staurenghi, G and Sadda, SR},
title = {Standardizing Measurement of cRORA (Complete Retinal Pigment Epithelial and Outer Retinal Atrophy)- CAM Report 8.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.01.017},
pmid = {41621805},
issn = {2468-6530},
abstract = {PURPOSE: To highlight the role of en face OCT in the measurement of choroidal hypertransmission defects (hyperTDs) in complete retinal pigment epithelial and outer retinal atrophy (cRORA), and to refine the definition of retinal pigment epithelium (RPE)-related alterations associated with cRORA.

DESIGN: Consensus meeting.

PARTICIPANTS: Panel of retina specialists, including retinal imaging experts, reading center leaders, and retinal histologists.

METHODS: As part of the Classification of Atrophy Meeting (CAM) program, an international group of experts analyzed and discussed the role of en face OCT in the assessment of cRORA. A structured study was conducted, consisting of an exercise to assess en face OCT cases, reviewed jointly during the 8[th] CAM meeting, and to explore the utility of this advanced tool for disease staging and progression. Additionally, definitions previously applied to RPE abnormalities were discussed and refined leading to modifications. The current report summarizes the methods employed during the consensus meeting and the outcomes achieved as pertains to the application of en face OCT for cRORA grading and simplification of the RPE assessment criteria.

MAIN OUTCOME MEASURE: Defining the role of en face OCT in the detection and quantification of hyperTDs, improving classification of cRORA, and refining the terminology related to RPE alterations to enhance grading consistency.

RESULTS: During the consensus case discussions, high levels of agreement were achieved for hyperTD detection using en face OCT. The CAM group affirmed the role of en face OCT as a critical adjunct to traditional B-scan analysis, for more precise measurement of the area of cRORA lesions and for distinguishing threshold cRORA from smaller incomplete (iRORA) lesions. Additionally, merger of RPE attenuation and RPE disruption into a unified category termed "abnormal RPE band" significantly reduced inter-reader variability, leading to greater consistency among graders.

CONCLUSIONS: The integration of en face OCT with cross-sectional B-scan imaging enhances the accurate classification and area measurement of early atrophic alterations in AMD, improving diagnostic consistency and lesion assessment. The consensus panel's adoption of the abnormal RPE band term as a unified category for RPE abnormalities may reduce confusion regarding the definition of RPE degeneration and has the potential to improve inter-reader variability.},
}

@article {pmid41620804,
year = {2026},
author = {Li, K and Tang, J and Zhang, Z and Li, X and Zheng, Y and Jiang, D and Sun, J},
title = {Global burden and cross-country inequalities of age-related eye diseases from 1990 to 2021: a comprehensive analysis of temporal trends and socioeconomic disparities.},
journal = {Eye and vision (London, England)},
volume = {13},
number = {1},
pages = {4},
pmid = {41620804},
issn = {2326-0254},
support = {LMS26F020026//Natural Science Foundation of Zhejiang Province/ ; },
abstract = {BACKGROUND: Age-related eye diseases (AREDs) are leading causes of visual impairment worldwide. With global population aging, understanding their epidemiological trends and socioeconomic disparities is crucial for public health planning and equitable resource allocation.

METHODS: We conducted a secondary epidemiological analysis of AREDs using data from the Global Burden of Disease (GBD) Study 2021. We evaluated years lived with disability (YLDs) and age-standardized YLD rates (ASYR) and conducted trend analysis using Joinpoint regression. Cross-country inequalities were assessed using the slope index of inequality (SII) and concentration index, with correlation and regression analyses examining associations with the socio-demographic index (SDI).

RESULTS: Global YLDs for AREDs increased from 78.503 to 100.006, while ASYR decreased from 112.815 to 92.803 per 100,000 populations between 1990 and 2021. Despite a global increase in the relative burden of glaucoma, both absolute and relative inequalities for age-related macular degeneration (AMD) and cataracts decreased. Low-SDI countries showed slight improvements in reducing these inequalities. The SII for AREDs improved in lower-SDI countries between 1990 and 2021, with reductions in AMD (from - 9.250 to - 6.033), cataract (from - 258.131 to - 173.762), and glaucoma (from - 21.090 to - 20.064). The concentration index for AMD and cataract decreased from - 0.167 and - 0.335 in 1990 to - 0.129 and - 0.272 in 2021, respectively, while the concentration index for glaucoma increased from - 0.208 to - 0.263, Regional disparities in the AREDs burden were evident, with most regions showing improved inequality in lower-SDI countries as reflected in both the SII and concentration index.

CONCLUSIONS: Despite global improvements in the relative burden of AREDs, significant socioeconomic and geographical inequalities persist, particularly in low-SDI regions. Targeted public health strategies and strengthened eye care systems are urgently needed to address these disparities and achieve equitable eye health outcomes worldwide.},
}

@article {pmid41620512,
year = {2026},
author = {Alqassab, AIM and Luque-Nieto, MÁ and Mohammed, MA},
title = {Identification of multiple ocular diseases using a hybrid quantum convolutional neural network with fundus images.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-38063-z},
pmid = {41620512},
issn = {2045-2322},
support = {PID2023-146540OB-C43//Ministerio de Ciencia e Innovación/ ; },
abstract = {Ocular diseases remain a major cause of vision impairment globally, making early and accurate diagnosis essential. This study presents a novel diagnostic model for identifying seven common ocular conditions age-related macular degeneration, glaucoma, hypertension, diabetic retinopathy, myopia, cataracts, and other pathologies using clinical fundus images. To improve image quality, Anisotropic Diffusion Filtering and Wavelet Transform are applied for hue and contrast enhancement. Data imbalance is addressed through targeted augmentation techniques. The core of the model is a hybrid Quantum Convolutional Neural Network (QCNN), which integrates quantum convolutional pooling into a classical CNN architecture to boost feature extraction and classification. Evaluated on the OIA-ODIR dataset, the proposed model outperformed benchmarks such as Fundus-DeepNet, Inception-v4, VGG16 with SGD, and ResNet-101. It achieved 94% classification accuracy, along with substantial gains in precision, recall, and F1-score. These results confirm the model's effectiveness and its potential for supporting early, multi-disease ocular diagnosis in clinical settings.},
}

@article {pmid41619249,
year = {2026},
author = {Hiles, JD and Deri, O and Sishtla, K and Bear, JC and Cockcroft, JK and Opara, EI and Al-Kinani, AA and Alany, RG and Corson, TW and Schwikkard, SL},
title = {Sulphur Analogues of Homoisoflavonoids as Potential Treatments for Neovascular Eye Diseases.},
journal = {ChemMedChem},
volume = {21},
number = {2},
pages = {e202500824},
pmid = {41619249},
issn = {1860-7187},
support = {R01EY025641/MH/NIMH NIH HHS/United States ; RGPIN-2025-04563//Retina Research Foundation, Canada Foundation for Innovation, and Natural Sciences and Engineering Research Council/ ; },
mesh = {Humans ; *Angiogenesis Inhibitors/chemistry/pharmacology/chemical synthesis ; Cell Proliferation/drug effects ; *Isoflavones/chemistry/pharmacology/chemical synthesis ; Endothelial Cells/drug effects ; Structure-Activity Relationship ; Cell Line ; *Sulfur/chemistry/pharmacology ; Molecular Structure ; *Neovascularization, Pathologic/drug therapy ; Dose-Response Relationship, Drug ; Cyclooxygenase 2/metabolism ; },
abstract = {Treatment of neovascular eye diseases like age-related macular degeneration require a compound that is not toxic to ocular cells, that can reduce inflammation and inhibit angiogenesis. Homoisoflavonoids, naturally occurring compounds isolated primarily from the Hyacinthaceae sub-family of plants, have shown promise as anti-inflammatories and inhibitors of angiogenesis. A series of sulphur analogues, (3-benzylidene thiochroman-4-ones), were synthesised via a three-step procedure. These compounds were evaluated for selectivity towards endothelial cells over non-endothelial cells and their ability to inhibit COX-II over COX-I.Their potential anti-angiogenic activity was assessed using the Matrigel tube formation assay. (3Z)-3-[(3-bromophenyl)methylidene]-6-methoxy-2,3-dihydro-4H-1-benzothiopyran-4-one (10) was most active with respect to anti-proliferation against human retinal endothelial cells (HREC cells) (GI50 3.07 μM). All demonstrated selectivity with all GI50 values against retinal pigment epithelial cell line ARPE-19 >100 µM, with the exception of (3Z)-6-bromo-3-[(4-nitrophenyl)methylidene]-2,3-dihydro-4H-1-benzothiopyran-4-one (12), which was not toxic to either. (3Z)-3-[(3-bromophenyl)methylidene]-6-methoxy-2,3-dihydro-4H-1-benzothiopyran-4-one (10) showed significant reduction in angiogenesis properties in a Matrigel-based tube formation assay (38.79%, 5 µM, 56.41%, 10 µM). (3Z)-6-bromo-3-[(3-bromophenyl)methylidene]-2,3-dihydro-4H-1-benzothiopyran-4-one (7) was found to be the most active against COX-II with inhibition of 22.7 % (4.35 nM). The 3-benzylidene thiochroman-4-ones show promise as antiangiogenic agents, but limited selectivity to COX-II over COX-I.},
}

Humans
*Angiogenesis Inhibitors/chemistry/pharmacology/chemical synthesis
Cell Proliferation/drug effects
*Isoflavones/chemistry/pharmacology/chemical synthesis
Endothelial Cells/drug effects
Structure-Activity Relationship
Cell Line
*Sulfur/chemistry/pharmacology
Molecular Structure
*Neovascularization, Pathologic/drug therapy
Dose-Response Relationship, Drug
Cyclooxygenase 2/metabolism

@article {pmid41619168,
year = {2026},
author = {Raczynska, D and Ernest, J and Baumane, K and Sagong, M and Akiyama, K and Rauschning, W and Vajas, A and Nowosielska, A and Dusova, J and Majtánová, N and Oleksy, P and Kuneva, I and Resch, M and Lange, N and Briede, E and Bajdik, B and Jeong, A and Kozub, B and Papp, A},
title = {Therapeutic Equivalence of Eyluxvi (Aflibercept) to Eylea in Neovascular Age-Related Macular Degeneration: ALTERA Trial (Randomized).},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41619168},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aimed to evaluate the efficacy and safety of Eyluxvi, an aflibercept biosimilar, compared with reference Eylea in patients with neovascular age-related macular degeneration (nAMD).

METHODS: This phase 3, multicenter, randomized, double-masked, parallel-group study enrolled 431 patients at 79 sites across 12 countries. Patients were randomized 1:1 to receive intravitreal Eyluxvi or Eylea (2 mg) every 4 weeks through week 12, then every 8 weeks through week 48. The primary endpoint was change from baseline in best corrected visual acuity (BCVA) at week 8.

RESULTS: The week 8 least-squares mean BCVA change was 5.771 letters with Eyluxvi vs 7.863 letters with Eylea (difference - 2.092 [95% confidence interval (CI) - 3.431 to - 0.753]). This equivalence was maintained through week 52. Week 52 adjusted mean changes were comparable for central subfield thickness (CST) (difference - 4.742 μm [95% CI - 22.006 to 12.521]) and choroidal neovascularization (CNV) area (difference 0.233 mm[2] [95% CI - 0.724 to 1.191]). Safety profiles and immunogenicity were similar between groups.

CONCLUSION: This study demonstrated therapeutic equivalence between Eyluxvi and Eylea in nAMD treatment, with comparable anatomical outcomes and safety profiles. These findings support the development of Eyluxvi as an aflibercept biosimilar, potentially increasing treatment accessibility for patients with nAMD.

TRIAL REGISTRATION: EudraCT Identifier 2021-004530-11.},
}

@article {pmid41618563,
year = {2026},
author = {Cui, M and Cheng, SY and Liang, J and McGowan, J and Xu, M and Xu, G and Luo, L and Wu, J and Harman, CD and Jacobson, AL and Kapeller, LE and Mayes, MA and Namkung, S and Sharma, T and Leland, TB and Zhang, F and Yip, M and Rossmiller, B and Xue, T and Chen, X and Boonying, W and Lotun, A and Wang, D and Su, Q and Xie, J and Wei, Y and Rothstein, AM and Gregory-Ksander, MS and Komaromy, A and Tian, B and Lin, H and Punzo, C and Tai, PWL and Gao, G},
title = {Modification of the VP1u region boosts transduction of adeno-associated virus vectors for ocular gene therapy.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.01.029},
pmid = {41618563},
issn = {1525-0024},
abstract = {Adeno-associated virus (AAV) capsids that can confer efficient and safe gene therapy of the retina remain unmet needs. In this study, we isolated a library of natural capsids from human tissues and identified two variants that conferred strong transduction of retinal tissues following intravitreal injections of mice and non-human primates. Interestingly, the defining amino acids among the two variants are located within the luminal VP1 unique (VP1u) region of the capsid. Combining these defining residues into a single capsid (AAV2.MC1) had an additive effect. We demonstrated that the MC1 modification enhances intracellular trafficking and nuclear entry. Importantly, we provide proof-of-concept that the AAV2.MC1 capsid can deliver an anti-VEGF transgene to treat wet age-related macular degeneration. Finally, we demonstrate that the modification can also be grafted onto other AAV serotypes to boost baseline transduction. These findings open up new avenues for capsid modification through targeted alterations of the VP1u region.},
}

@article {pmid41617984,
year = {2026},
author = {Bailey, C and Lange, C and Chaudhary, V and Lanzetta, P and Oubraham, H and Kirchner, M and Machewitz, T and Allmeier, H and Zhang, X and Hasanbasic, Z and Munk, MR and , },
title = {SPECTRUM: early clinical experience from the first global real-world study of aflibercept 8 mg in patients with neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41617984},
issn = {1476-5454},
}

@article {pmid41617934,
year = {2026},
author = {Bo, N and Ding, Y},
title = {Estimation of the interpretable heterogeneous treatment effect with causal subgroup discovery in survival outcomes.},
journal = {Lifetime data analysis},
volume = {32},
number = {1},
pages = {11},
pmid = {41617934},
issn = {1572-9249},
support = {R01GM141076/GM/NIGMS NIH HHS/United States ; },
mesh = {Humans ; Macular Degeneration/drug therapy/genetics ; Treatment Outcome ; Survival Analysis ; Computer Simulation ; Precision Medicine/methods ; Randomized Controlled Trials as Topic ; Antioxidants/therapeutic use ; Treatment Effect Heterogeneity ; },
abstract = {Estimating heterogeneous treatment effects (HTE) for survival outcomes has gained increasing attention in precision medicine, as it captures variations in treatment efficacy among patients or subgroups. However, most existing methods conduct post-hoc subgroup identifications rather than simultaneously estimating HTE and identifying causal subgroups. In this paper, we propose an interpretable HTE estimation framework that integrates meta-learners with tree-based methods to estimate the conditional average treatment effect (CATE) for survival outcomes and identify predictive subgroups simultaneously. We evaluated the performance of our method through extensive simulation studies. We also demonstrated its application in a large randomized controlled trial (RCT) for age-related macular degeneration (AMD), a progressive polygenic eye disease, to estimate the HTE of an antioxidant and mineral supplement on time-to-AMD progression and to identify genetically defined subgroups with enhanced treatment effects. Our method offers a direct interpretation of the estimated HTE and provides evidence to support precision healthcare.},
}

Humans
Macular Degeneration/drug therapy/genetics
Treatment Outcome
Survival Analysis
Computer Simulation
Precision Medicine/methods
Randomized Controlled Trials as Topic
Antioxidants/therapeutic use
Treatment Effect Heterogeneity

@article {pmid41615526,
year = {2026},
author = {Ciarmatori, N and Cartabellotta, A and Adamo, GG and Biffi, C and Talli, PM and Pellegrini, M and Mura, M},
title = {Bilateral implantation of extended depth of focus intraocular lens in patients with early or intermediate age-related macular degeneration.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {87},
pmid = {41615526},
issn = {1573-2630},
support = {Investigator Initiated Trial Grant (IIT#75441181)//Alcon/ ; },
mesh = {Humans ; Male ; Female ; Prospective Studies ; *Visual Acuity/physiology ; Aged ; *Lenses, Intraocular ; *Macular Degeneration/complications/surgery/physiopathology/diagnosis ; *Vision, Binocular/physiology ; *Depth Perception/physiology ; *Lens Implantation, Intraocular/methods ; Patient Satisfaction ; Aged, 80 and over ; Prosthesis Design ; Middle Aged ; Follow-Up Studies ; Refraction, Ocular/physiology ; *Phacoemulsification/methods ; },
abstract = {PURPOSE: To evaluate the visual outcomes, dysphotopsia profile, and patient satisfaction following bilateral implantation of the AcrySof IQ Vivity intraocular lens (IOL) in patients with early or intermediate age-related macular degeneration (AMD).

METHODS: Prospective, single-center study. 24 patients (48 eyes) with bilateral cataract and early or intermediate AMD who underwent bilateral implantation of the AcrySof IQ Vivity IOL. The primary outcome was monocular corrected distance visual acuity (mCDVA). Secondary endpoints were distance-corrected and unaided monocular and binocular visual acuity at 4 m, 66 cm, and 40 cm, monocular defocus curve, subjective dysphotopsia (McAlinden QoV questionnaire) and haloes perception (Aston Halometer), visual function (Catquest-9SF), and spectacle independence (IOLSAT).

RESULTS: At 3 months postoperatively, mCDVA improved significantly from 0.30 to 0.00 logMAR (p < 0.001). Binocular uncorrected distance and intermediate visual acuities of ≤ 0.2 logMAR were achieved by 23 (95.8%) and 17 (70.8%) patients, respectively. The defocus curve showed visual acuity of 0.2 logMAR across a range of + 1.40 D to -1.72 D. Bothersome dysphotopsias significantly decreased, with QoV scores improving from 58.5 (IQR: 26.1-66.5) to 0.00 (IQR: 0.00-14.3) (p < 0.05). The mean halo eccentricity was 0.50 ± 0.08 degrees. Spectacle independence was reported by 22 (91.7%), 20 (83.3%), and 13 (54.2%) patients for distance, intermediate, and near tasks, respectively. Overall, 22 (91.7%) patients reported postoperative satisfaction.

CONCLUSION: The AcrySof IQ Vivity IOL demonstrated favourable outcomes in patients with early or intermediate AMD, offering a meaningful range of spectacle-free vision with minimal photic phenomena.},
}

Humans
Male
Female
Prospective Studies
*Visual Acuity/physiology
Aged
*Lenses, Intraocular
*Macular Degeneration/complications/surgery/physiopathology/diagnosis
*Vision, Binocular/physiology
*Depth Perception/physiology
*Lens Implantation, Intraocular/methods
Patient Satisfaction
Aged, 80 and over
Prosthesis Design
Middle Aged
Follow-Up Studies
Refraction, Ocular/physiology
*Phacoemulsification/methods

@article {pmid41613944,
year = {2025},
author = {Marmorstein, AD and Scruggs, BA and Knudsen, T and Hill, M and Kopp, FN and Trncic, E and Korda, D and Atherton, E and Berger, A and Finnemann, SC and Gandhi, J and Iezzi, R},
title = {Degradable fibrin hydrogels for transplantation of iPSC-derived retinal pigment epithelial cell monolayers.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1739620},
pmid = {41613944},
issn = {2296-634X},
abstract = {Death or dysfunction of retinal pigment epithelium (RPE) cells occurs in age-related macular degeneration (AMD) and certain inherited retinal dystrophies (IRDs). Induced-pluripotent stem cell (iPSC) derived-RPE have been used in early-stage clinical trials to treat AMD and IRDs by injecting them as a cell suspension or monolayers. While RPE transplant shows therapeutic potential, issues ranging from failure to repopulate the entire treatment area, clumping and monolayer folding, and a foreign body response to the support have been reported. We've shown that RPE can be grown on high concentration (>30 mg/mL) degradable fibrin hydrogels, and that cell free fibrin hydrogels implanted in the subretinal space degrade without causing inflammation. Here we describe manufacture and surgical implantation of degradable fibrin hydrogels carrying iPSC-RPE into a porcine model of geographic atrophy (GA). Large (15.25 × 58.42 × 0.2 mm) fibrin gel blanks were produced by injection molding, and iPSC-RPE were grown on their surface. Using a mechanical punch, the blank was subdivided into 1.5 × 5.0 × 0.2 mm doses, which fit a custom tool used for storage and surgical placement. Following aseptic packaging, RPE and gels were stable at 37 °C for at least 7 weeks. When transplanted into a pig model of GA, the fibrin scaffold degraded in <1 month and the iPSC-RPE provided partial rescue from GA as assessed by preservation of photoreceptors and blood flow in the choriocapillaris. We conclude that iPSC-RPE delivered on degradable fibrin hydrogels represent a potentially safe and effective approach to RPE transplantation.},
}

@article {pmid41613191,
year = {2025},
author = {Shanidze, NM and Velisar, A},
title = {Cancellation of the vestibulo-ocular reflex during smooth pursuit in patients with maculopathy.},
journal = {Frontiers in neurology},
volume = {16},
number = {},
pages = {1632527},
pmid = {41613191},
issn = {1664-2295},
abstract = {INTRODUCTION: Macular degeneration is associated with loss of central vision, including the fovea. Central visual field loss is associated with impaired smooth pursuit eye movements, and the associated scotoma can lead to target disappearance which may or may not be transient. While smooth pursuit in and of itself does not require a foveal position signal, suppression of the vestibuloocular reflex (VOR) needed during combined eye and head pursuit relies on the fovea for appropriate calibration. Prior work has shown that target extinction during, or even at the beginning of the trial does not affect the dynamics of the eye or head responses necessary for pursuit. These findings suggest that the potential disappearance of the target into the scotoma during pursuit can be overcome, particularly when both eye and head movements are used. The objective of this study was to test the hypothesis that head-unrestrained smooth pursuit deficits in CFL are at least partially related to individuals' inability to cancel their VOR.

METHODS: We performed a secondary analysis of a previously published data set of head restrained and unrestrained pursuit of a 10 °/s target in 7 individuals with maculopathy (56-89 years) and 7 age-matched controls (61-78 years). We used a two-parameter linear regression model to quantify the eye-only pursuit (Kfix) and VOR (Kv) contributions to determine whether participants were able to effectively cancel the VOR to improve pursuit gain.

RESULTS: We observed reduced pursuit velocities in the head-unrestrained versus restrained smooth pursuit condition (Kfix < 1), particularly in the control group (CFL: Kfix = 0.90 ± 0.16; Control: Kfix = 0.74 ± 0.08). For VOR cancellation, Kv estimates did not deviate from -1 for either of our groups (CFL: Kv = -0.92 ± 0.09; Control: Kv = -0.98 ± 0.20), suggesting complete cancellation of the VOR during head-unrestrained pursuit. For the self-generated VOR experiment, participants in both groups had similar, near-one VOR gains (CFL: GainVOR = -1.00 ± 0.05; Control: GainVOR = -1.03 ± 0.02).

DISCUSSION: We confirmed that VOR responses to actively generated head movements were similarly intact in both groups. Our analyses of the pursuit data indicate that, regardless of visual function older adults attenuate eye-driven pursuit when the head is unrestrained (as compared to the restrained condition), and those with CFL fail to exploit residual VOR cancellation, helping to explain their persistent gaze-tracking deficits.},
}

@article {pmid41612003,
year = {2026},
author = {Bartolomeo, N and Kalyvianakis, KK and Schuetz, YP and Nascimbeni, AC and Castro, DG and Crozat, B and Barry, MP and Ambresin, A},
title = {Early Outcomes of Intravitreal Aflibercept 8 mg in Eyes Previously Treated with Aflibercept 2 mg for Neovascular Age-Related Macular Degeneration with AI-Based Biomarker Quantification.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41612003},
issn = {2193-8245},
abstract = {INTRODUCTION: To evaluate the early outcomes of aflibercept 8 mg (afl8) treatment in patients with neovascular age-related macular degeneration (nAMD) previously treated with aflibercept 2 mg (afl2).

METHODS: A retrospective, observational, monocentric Swiss study. Patients with nAMD who had received ≥ 3 consecutive afl2 injections and switched to afl8 because of persistent or recurrent fluids, or to extend treatment intervals, were included in the study. All patients started a loading phase of 3-monthly afl8 injections, followed by a treat-and-extend regimen. Outcome measures included changes in best-corrected visual acuity (BCVA), maximal pigment epithelial detachment (PED) height, central subfield thickness (CST), optical coherence tomography (OCT) biomarkers quantified using artificial intelligence, and treatment intervals until month 6.

RESULTS: Fifty-two eyes of 44 patients who concluded the loading phase were included in this analysis. Mean age was 80.2 ± 8.5 years; 73% of patients were females. At month 6, BCVA was unchanged, PED and CST height experienced a significant decrease by - 18.5 ± 12.9 μm (p = 0.0005) and - 14.0 ± 3.5 μm (p = 0.0042), respectively. Volumes of intraretinal fluid (IRF), subretinal fluid (SRF), and PED decreased (IRF: 4.4 ± 15.6-3.8 nl; SRF: 15.7 ± 35.7-10.3 ± 34.0 nl; PED: 268.2 ± 423.2-252.2 ± 484.1 nl). Mean treatment intervals increased by 1.7 ± 0.5 weeks from the last assigned interval and by 0.6 ± 0.2 weeks from previous maximal fluid-free intervals after switching (p = 0.0005 and p = 0.18, respectively). One mild vitritis was observed and resolved with vitrectomy and topical drops without decreased visual acuity.

CONCLUSION: Our real-world study supports the potential short-term benefits of afl8 in improving anatomical and durability outcomes in patients with recurrent nAMD. These findings also highlight the added value of data-driven evaluations. Long-term studies are needed to confirm the effectiveness and durability of afl8 in this population.},
}

@article {pmid41607454,
year = {2026},
author = {Walia, S and Morya, AK},
title = {Psychiatric disorders linked to visual impairment: A review of mental health challenges and interventions across age groups.},
journal = {World journal of psychiatry},
volume = {16},
number = {1},
pages = {111118},
pmid = {41607454},
issn = {2220-3206},
abstract = {The intersection of visual impairment and mental health has profound effects on quality of life and warrants attention from healthcare providers, educators, and policymakers. With 20 million children under the age of 14 affected globally, older adults also experience significant psychological impact including depression, anxiety, and cognitive impairment. The implications of vision-related challenges extend far beyond mere sight. Depression and anxiety, exacerbated by social isolation and reduced physical activity, underscore the need for comprehensive interventions that address both medical and psychosocial dimensions. By recognizing the profound impact of ocular morbidities like strabismus, myopia, glaucoma, and age-related macular degeneration on mental health and investing in effective treatments and inclusive practices, society can pave the way for a healthier, more equitable future for affected individuals. There is evidence that myopic children experience a higher prevalence of depressive symptoms compared to their normal peers, and interventions like the correction of strabismus can enhance psychological outcome - demonstrating the value of an integrated management approach.},
}

@article {pmid41604455,
year = {2026},
author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE},
title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons in C. elegans.},
journal = {Molecular biology of the cell},
volume = {},
number = {},
pages = {mbcE25110547},
doi = {10.1091/mbc.E25-11-0547},
pmid = {41604455},
issn = {1939-4586},
abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and C. elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for non-canonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.},
}

@article {pmid41603556,
year = {2026},
author = {Owsley, C and Gao, L and Gooden, L and Thomas, TN and Pu, J and Crosson, JN and Curcio, CA and McGwin, G and Kwon, M},
title = {Preserved Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration and Marked Loss in Late Stage: ALSTAR2.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {1},
pages = {58},
doi = {10.1167/iovs.67.1.58},
pmid = {41603556},
issn = {1552-5783},
mesh = {Humans ; Aged ; *Contrast Sensitivity/physiology ; Female ; Male ; Cross-Sectional Studies ; Visual Acuity/physiology ; Aged, 80 and over ; Middle Aged ; Disease Progression ; *Macular Degeneration/physiopathology ; *Wet Macular Degeneration/physiopathology ; *Geographic Atrophy/physiopathology ; },
abstract = {PURPOSE: To cross-sectionally compare parameters from the quick contrast sensitivity function (qCSF)-area under the log CSF (AULCSF) and sensitivity at each spatial frequency-in older eyes with normal macular health and early, intermediate, and late AMD. Our purpose was to determine whether qCSF could be a promising functional outcome measure in interventions designed to slow AMD progression from aging to late AMD.

METHODS: qCSF contrast sensitivity was measured at 1.0 to 18 cycles per degree (cyc/deg). Models evaluated the impact of diagnostic group on the AULCSF and individual spatial frequencies, adjusting for age and lens status. The AREDS nine-step classification system defined AMD presence and severity.

RESULTS: Eight hundred twenty-three eyes were studied: 383 normal macular health, 203 early AMD, 208 intermediate AMD, and 29 late AMD (23 geographic atrophy, six neovascular AMD). AULCSF decreased with increasing AMD severity; this was mostly attributable to the late AMD eyes having lower AULCSF than other groups. Late AMD eyes had significantly worse sensitivity at 1 and 1.5 cyc/deg compared to all other groups, with other groups having similar sensitivity. At frequencies near or just beyond the CSF peak (3-12 cyc/deg), late AMD eyes again had the worst sensitivity, with intermediate AMD eyes having slightly worse sensitivity than early AMD eyes. There were no group differences at 18 cyc/deg.

CONCLUSIONS: The qCSF will be most useful in trials studying the transition from intermediate AMD to late-stage AMD, rather than in studying the transition from aging to early and intermediate AMD.},
}

Humans
Aged
*Contrast Sensitivity/physiology
Female
Male
Cross-Sectional Studies
Visual Acuity/physiology
Aged, 80 and over
Middle Aged
Disease Progression
*Macular Degeneration/physiopathology
*Wet Macular Degeneration/physiopathology
*Geographic Atrophy/physiopathology

@article {pmid41566404,
year = {2026},
author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ},
title = {APOE genotype differentially modulates prion pathology in a mouse model.},
journal = {Acta neuropathologica communications},
volume = {14},
number = {1},
pages = {29},
pmid = {41566404},
issn = {2051-5960},
support = {R01 AG067478/AG/NIA NIH HHS/United States ; R01 AG0758401/AG/NIA NIH HHS/United States ; RF1 AG088226/AG/NIA NIH HHS/United States ; R01 AG067478/AG/NIA NIH HHS/United States ; R01 AG0758401/AG/NIA NIH HHS/United States ; RF1 AG088226/AG/NIA NIH HHS/United States ; },
abstract = {UNLABELLED: APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer’s disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2, ε3/ε3, and ε4/ε4 APOE-TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε422L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε222L mice performed significantly better than ε4/ε422L mice but significantly worse than ε3/ε322L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP[Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε222L and ε3/ε322L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε422L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε422L mice. ε4/ε422L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε222L, with ε3/ε322L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4-affected mechanisms: increased conversion and accumulation of PrP[Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4, the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-025-02207-5.},
}

@article {pmid41603341,
year = {2026},
author = {Wang, S and Wang, C and Hong, H and Tang, C and Yu, J and Wang, Q},
title = {An integrative multi-omics study reveals glutamine metabolism dysregulation connecting Alzheimer's disease and age-related macular degeneration.},
journal = {Journal of Alzheimer's disease : JAD},
volume = {},
number = {},
pages = {13872877261418263},
doi = {10.1177/13872877261418263},
pmid = {41603341},
issn = {1875-8908},
abstract = {BackgroundAlzheimer's disease (AD) and age-related macular degeneration (AMD) are two common neurodegenerative diseases with many similar pathological features, but their shared metabolic characteristics have not been fully elucidated.ObjectiveThis study aims to explore the shared metabolic pathways between AD and AMD using an integrated multi-omics strategy.MethodsWe incorporated Mendelian randomization (MR), bulk and single-cell transcriptomics, and targeted metabolomics to investigate the metabolic links.ResultsThrough MR, we found elevated genetically inferred glutamine concentrations were correlated with a lower likelihood of AD but a higher likelihood of AMD. Using transcriptomic profiling, we detected 19 common differentially expressed genes associated with glutamine and glutamate metabolism, such as GLS. Analysis of single-cell RNA sequencing data revealed that GLS displays distinct cell-type expression patterns. Targeted metabolomic profiling in APP/PS1 mice at 5 months of age provided additional evidence for alterations in glutamine metabolism. The degree of metabolic changes in the eyes was higher than that in the cortex and hippocampus, and the prominent eyes may be an early indicator of neurodegenerative metabolic dysfunction.ConclusionsOverall, these findings suggest that glutamine metabolism disorders represent a convergent mechanism between AD and AMD. Our findings shed light on the overlapping metabolic pathways linking AD and AMD, underscoring the value of ocular biomarkers as promising tools for early disease detection.},
}

@article {pmid41603251,
year = {2026},
author = {Li, M and Yue, Y and Wu, S and He, X and Song, J and Ma, S and Zhang, H and Xu, C and Chen, S and Huang, Y and Xie, S and Yan, H},
title = {DNA Nanoflower LYTACs Enable Efficient VEGF Degradation and Verteporfin Loading for Combined Therapy of Wet Age-Related Macular Degeneration.},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
volume = {},
number = {},
pages = {e15852},
doi = {10.1002/advs.202515852},
pmid = {41603251},
issn = {2198-3844},
support = {82330031//National Natural Science Foundation of China/ ; 32270892//National Natural Science Foundation of China/ ; TJYXZDXK-3-004A//Tianjin Key Medical Discipline Construction Project/ ; },
abstract = {Wet age-related macular degeneration (wAMD), characterized by pathological choroidal neovascularization (CNV), is a leading cause of irreversible vision loss in the elderly. The current standard treatment-anti-vascular endothelial growth factor (VEGF) therapy-effectively manages neovascularization in many patients. However, some experience suboptimal responses, and frequent intravitreal injections raise safety concerns. Photodynamic therapy is another effective option for treating wAMD, but it can lead to an increase in reactive VEGF after the procedure, resulting in CNV recurrence. In response to these challenges, we propose an integrated approach that combines a DNA nanoflower VEGF degrader with photodynamic therapy. The DNA nanoflower consists of numerous aptamer-based lysosome-targeted chimaera (LYTAC) units, which drive extracellular VEGF in the lesion area to the lysosome for degradation. Simultaneously, the DNA nanoflower acts as a carrier for verteporfin (VER), a clinically used photosensitizer. The resulting nanoflower, named NF@VER, generates reactive oxygen species under near-infrared light to induce endothelial cell death. These combined effects on endothelial cells effectively block VEGF-induced CNV in vivo, without causing noticeable side effects. Overall, this innovative approach presents a precise and effective strategy for treating wAMD, reducing the risk of VEGF reactivation-induced CNV recurrence, and minimizing the systemic side effects associated with photodynamic therapy.},
}

@article {pmid41602785,
year = {2026},
author = {Khorrami-Nejad, M and Naroo, SA and Oklla, A and Narooie-Noori, F},
title = {Blue-light-filtering spectacle lenses in managing vision-related symptoms: an updated review.},
journal = {Therapeutic advances in ophthalmology},
volume = {18},
number = {},
pages = {25158414251412798},
pmid = {41602785},
issn = {2515-8414},
abstract = {Blue light, emitted by natural and artificial sources such as digital screens, has raised concerns regarding its impact on ocular health, visual comfort, and circadian rhythms. Prolonged exposure has been linked to digital eye strain (DES), visual fatigue, potential retinal damage, and sleep disturbances. Blue-light-filtering spectacle lenses have been developed to mitigate these effects by reducing short-wavelength blue light transmission, but their efficacy remains debated. Studies indicate that these lenses have minimal or no significant impact on contrast sensitivity, color discrimination, and task performance, with visual outcomes comparable to standard lenses. While some research suggests minor benefits in reducing DES and visual fatigue in specific populations, most studies report no significant differences. This highlights the multifactorial nature of DES. Experimental evidence supports the potential for blue-light-filtering spectacle lenses to reduce oxidative stress and phototoxicity in retinal cells, which may offer protection against retinal damage and age-related macular degeneration (ARMD). Additionally, these lenses show promise in neurological and psychological domains, including reduced migraine frequency, alleviation of mania symptoms, and improved sleep quality through circadian rhythm regulation. However, subjective sleep improvements are often not supported by objective measures. In summary, blue-light-filtering spectacle lenses may provide benefits in retinal protection, sleep regulation, and neurological health. However, their effectiveness in reducing visual fatigue, enhancing task performance, and preventing ARMD remains inconclusive. Further research with standardized methodologies and larger sample sizes is needed to clarify their clinical and everyday utility.},
}

@article {pmid41601834,
year = {2025},
author = {Jiang, L and Jiang, X and Shi, X and Hu, X and Song, C and Yang, W and Tong, Y},
title = {Educational performance of TikTok short videos for age related macular degeneration and its link to user engagement.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1751545},
pmid = {41601834},
issn = {2296-858X},
abstract = {BACKGROUND: To systematically evaluate the information quality, reliability, and content characteristics of short videos related to age-related macular degeneration on the Chinese mainland version of TikTok, filling the research gap in this field and providing references for ophthalmic health education and platform information governance.

METHODS: This cross-sectional study was conducted on October 15, 2025, by searching the keyword "" on TikTok. The top 200 videos under "comprehensive ranking" were screened, and 196 videos meeting the eligibility criteria were ultimately included. Content integrity was evaluated following the American Academy of Ophthalmology guidelines and the Goobie framework. Video quality was assessed using the DISCERN instrument and the PEMAT-A/V tool. Statistical analyses were performed in IBM SPSS Statistics 27.0, with inter-rater reliability measured by the intraclass correlation coefficient. Differences among groups and associations between variables were examined using ANOVA and correlation analysis.

RESULTS: The overall quality of the included videos was moderate, with a median DISCERN tool score of 48.00 and a median Overall quality score of 3.00. The Understandability score was relatively high (median 84.62%), whereas the Actionability score was lower (median 75.00%). Videos uploaded by the Non-Profit group showed the highest quality (mean DISCERN tool score 59.13 ± 2.50), followed by the Medical group. The Non-Medical and For-Profit groups demonstrated the lowest quality, with statistically significant differences among groups (P < 0.05). Quality metrics were moderately positively correlated with user engagement metrics. The correlation coefficients between reliability and engagement were r = 0.48-0.54 (P < 0.05). Video duration showed a mild positive correlation with both quality and engagement (r = 0.23-0.30, P < 0.05). Inter-rater reliability was good (intraclass correlation coefficient = 0.839-0.947, P < 0.001).

CONCLUSION: Age-related macular degeneration videos on TikTok showed moderate overall quality, with content emphasizing clinical concerns but neglecting basic knowledge. Information quality varied by uploader source, with non-profit organizations and medical professionals providing most high-quality content. Higher-quality videos tended to receive greater user engagement, suggesting that platform algorithms may preferentially spread better educational material. These findings provide empirical support for improving science communication on this disease and strengthening information quality management on digital platforms.},
}

@article {pmid41601821,
year = {2025},
author = {Zhang, S and Zhang, X and Wang, Z and Shi, W and Ren, Z and Wang, Y and Jia, Q and Li, Y and Guo, Y and Li, Z},
title = {Multimodal imaging for early drusen detection: RM-SLO as a promising imaging approach.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1703332},
pmid = {41601821},
issn = {2296-858X},
abstract = {PURPOSE: This study aimed to evaluate the diagnostic performance of retro-mode scanning laser ophthalmoscopy (RM-SLO) in detecting drusen compared to conventional multimodal imaging. Additionally, it sought to explore the imaging characteristics of RM-SLO for early age-related macular degeneration (AMD).

METHODS: In this cross-sectional study, 192 patients (263 eyes) were examined using color fundus photography (CFP), optical coherence tomography (OCT), fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), and RM-SLO. Three retinal specialists independently reviewed all images for the presence of drusen. Detection rates across modalities were compared using Cochran's Q-test, and imaging characteristics of hard and soft drusen were described.

RESULTS: RM-SLO detected drusen in 102 eyes (38.78%). This detection rate was significantly higher compared to other methods such as OCT (22.05%), CFP (8.37%), FFA (5.32%), and FAF (4.18%) (all p < 0.0001 vs. RM-SLO). OCT was superior to CFP, FAF, and FFA (p < 0.0001); CFP had statistically significant differences from FFA and FAF (p = 0.039; p = 0.001). While FFA did not reveal any statistically significant differences from FAF (p = 0.453). RM-SLO provided a clear pseudo-three-dimensional visualization, enabling the identification of both hard and soft drusen, including small lesions that were not captured by other modalities.

CONCLUSION: RM-SLO demonstrates superior sensitivity and imaging clarity for drusen detection compared to conventional multimodal approaches. Its ability to visualize small and morphologically distinct drusen highlights its potential as a promising tool for early AMD screening and clinical management.},
}

@article {pmid41599848,
year = {2026},
author = {Abouhish, H and Shalaby, L and Elzayat, O and Peddireddy, N and Tawfik, A},
title = {Modulating One-Carbon Metabolism with B-Vitamins to Protect the Retinal Barrier and Prevent Retinal Degeneration.},
journal = {Nutrients},
volume = {18},
number = {2},
pages = {},
doi = {10.3390/nu18020236},
pmid = {41599848},
issn = {2072-6643},
mesh = {Animals ; *Retinal Degeneration/prevention & control/etiology ; Mice, Inbred C57BL ; *Vitamin B 12 Deficiency/blood ; Homocysteine/blood ; Vitamin B 12/administration & dosage/blood/pharmacology ; Mice ; *Vitamin B Complex/pharmacology/administration & dosage ; *Blood-Retinal Barrier/drug effects/metabolism ; *Carbon/metabolism ; Disease Models, Animal ; Male ; Cystathionine beta-Synthase/genetics ; Vitamin B 6/administration & dosage ; },
abstract = {BACKGROUND/OBJECTIVES: Vitamin B12 deficiency is increasingly recognized as a contributor in both vascular and neurodegenerative aging-related disorders. Its deficiency disrupts one-carbon metabolism, leading to impaired homocysteine (Hcy) cycling. Elevated Hcy is a well-established risk factor for vascular dysfunction. Previously, we established that elevated Hcy contributes to aging retinal diseases and plays a central role in blood retinal barrier (BRB) dysfunction. Building on this foundation, the present study examines how B-vitamin deficiency disrupts one-carbon metabolism and whether restoring these vitamins can serve as a preventive or therapeutic strategy. Since B-vitamins (B6, B9, and B12) are crucial cofactors in the metabolism of Hcy, we investigated how dietary changes in these vitamins affect serum Hcy levels and retinal vascular integrity in mice.

METHODS: C57BL/6- Wild-type (WT) and cbs[+/-] mice (Cystathionine Beta-Synthase heterozygotes, common mouse model for elevated Hcy) were fed specially formulated diets, which contained different levels of B-vitamins (normal, deficient (B-Vit (-)) or enriched (B-Vit (+)). Initially, two groups of mice were placed on either a normal or a deficient diet. After 12-16 weeks, the success of the diet regimes was confirmed by observing serum B12 deficiency in the B-Vit (-) group, along with elevated Hcy levels. Subsequently, a subgroup of the B-Vit (-) mice was switched to an enriched diet. The BRB integrity was evaluated in living mice using fluorescein angiography (FA), optical coherence tomography (OCT), and in the perfused mice retinas with Western blot analysis of leaked retinal albumin and tight junction proteins (occludin and ZO-1) levels.

RESULTS: The B-vitamin deficiency caused significant drop in serum vitamin B12 and an increase in plasma Hcy, leading to vascular leakage, altered retinal thickness, choroidal neovascular changes, increased retinal albumin leak, and decreased tight junction protein expression, indicating BRB disruption, which was restored with B-vitamin supplementation.

CONCLUSIONS: a long-term deficiency of vitamins B6, B9, and B12 can lead to disruptions in the BRB. However, supplementation with these B-vitamins has the potential to reverse these effects and help maintain the integrity of BRB. This under-score the significance of one-carbon metabolism for retinal health and suggests that ensuring adequate levels of B-vitamins may aid in preventing aging retinal diseases with BRB disruption such as diabetic retinopathy and age-related macular degeneration.},
}

Animals
*Retinal Degeneration/prevention & control/etiology
Mice, Inbred C57BL
*Vitamin B 12 Deficiency/blood
Homocysteine/blood
Vitamin B 12/administration & dosage/blood/pharmacology
Mice
*Vitamin B Complex/pharmacology/administration & dosage
*Blood-Retinal Barrier/drug effects/metabolism
*Carbon/metabolism
Disease Models, Animal
Male
Cystathionine beta-Synthase/genetics
Vitamin B 6/administration & dosage

@article {pmid41598408,
year = {2026},
author = {Sarna, M and Waszczykowska, A},
title = {Submacular Hemorrhage Management: Evolving Strategies from Pharmacologic Displacement to Surgical Intervention.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/jcm15020469},
pmid = {41598408},
issn = {2077-0383},
support = {no//Medical University of Lodz/ ; },
abstract = {Background: Submacular hemorrhage (SMH) is a vision-threatening condition most associated with neovascular age-related macular degeneration (nAMD), although it may also arise from polypoidal choroidal vasculopathy, pathological myopia, retinal vascular diseases, trauma, and systemic factors. Rapid management is essential because subretinal blood induces photoreceptor toxicity, clot organization, and fibroglial scarring, leading to irreversible visual loss. The choice and urgency of treatment depend on hemorrhage size, duration, and underlying pathology, and the patient's surgical risk category, which can influence the invasiveness of the selected procedure. This review aims to provide an updated synthesis of recent advances in the surgical and pharmacological management of SMH, focusing on evidence from the past five years and comparing outcomes across major interventional approaches. Methods: A narrative review of 27 recent clinical and multicentre studies was conducted. The included literature evaluated pneumatic displacement (PD), pars plana vitrectomy (PPV), subretinal or intravitreal recombinant tissue plasminogen activator (rtPA), anti-VEGF therapy, and hybrid techniques. Studies were analyzed about indications, surgical methods, timing of intervention, anatomical and functional outcomes, and complication and patient risk stratification. Results: Outcomes varied depending on the size and duration of hemorrhage, as well as the activity of underlying macular neovascularization. PD with intravitreal rtPA was reported as effective for small and recent SMH. PPV combined with subretinal rtPA, filtered air, and anti-VEGF therapy demonstrated favorable displacement and visual outcomes in medium to large hemorrhages or those associated with active nAMD. Hybrid techniques further improved clot mobilization in selected cases. Across studies, delayed intervention beyond 14 days correlated with reduced visual recovery due to blood organization and photoreceptor loss. Potential risks, including recurrent bleeding and rtPA-associated toxicity, were reported but varied across studies. Conclusions: Management should be individualized, considering hemorrhage characteristics and surgical risk. Laser therapy, including PDT, may serve as an adjunct in the perioperative or postoperative period, particularly in PCV patients. Early, tailored intervention typically yields the best functional outcomes.},
}

@article {pmid41598388,
year = {2026},
author = {Ongun, GT and Yağcı, R},
title = {The Effect of Intravitreal Ranibizumab Injection on Retinal Nerve Fiber Layer Thickness and Optic Disc Parameters.},
journal = {Journal of clinical medicine},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/jcm15020449},
pmid = {41598388},
issn = {2077-0383},
abstract = {Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the clinical records of 60 patients who received intravitreal ranibizumab injections for macular edema secondary to AMD, DME, or RVO between October 2014 and January 2016. All patients received intravitreal ranibizumab at a dose of 0.5 mg. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were recorded at baseline and during follow-up. RNFL thickness and optic disc parameters were assessed using optical coherence tomography (OCT) and Heidelberg Retina Tomograph III (HRT-3). Measurements were obtained before treatment and at 1 week, 1 month, 3 months, and 6 months after injection. Comparisons were performed within and between disease groups. Results: Of the 60 patients, 31 (51.7%) had DME, 20 (33.3%) had AMD, and 9 (15.0%) had RVO. Best-corrected visual acuity improved significantly during the follow-up period. Mean RNFL thickness measured by OCT showed a significant reduction in the DME and RVO groups (p = 0.0001 and p = 0.043, respectively). In contrast, no significant changes in RNFL thickness were detected using HRT-3, and no consistent alterations in other optic disc parameters were observed. Changes in optic disc parameters varied among disease groups. Conclusions: Intravitreal ranibizumab treatment was associated with a reduction in mean RNFL thickness measured by OCT in patients with DME and RVO during a six-month follow-up period, whereas no corresponding RNFL thinning was detected using HRT-3 in any disease group. The observed optic disc parameter changes appeared to be disease specific. Given the absence of untreated control eyes and the exclusion of patients with glaucoma, these findings apply only to non-glaucomatous eyes and should not be extrapolated to patients with glaucoma. Further prospective studies with larger cohorts, appropriate control groups, and longer follow-up durations are warranted to clarify the long-term effects of anti-VEGF therapy on the optic nerve.},
}

@article {pmid41598179,
year = {2025},
author = {Li, B and Addo, EK and Chang, FY and Guo, S and Awuni, M and Conway, E and Ying, J and Ramos, D and Bernstein, PS},
title = {Retinal Carotenoid Supplementation Increases HDL Cholesterol in Humans and Mice.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/life16010023},
pmid = {41598179},
issn = {2075-1729},
support = {EY-11600, EY-14800//NIH grants EY-11600, EY-14800, by the BrightFocus Foundation, and by unrestricted departmental funds from Research to Prevent Blindness/ ; },
abstract = {Carotenoid supplementation may reduce the risk of age-related macular degeneration (AMD). These retinal nutrients are hydrophobic molecules obtained from the diet that are transported to the retina through high-density lipoprotein (HDL) complexes. HDL cholesterol is a recognized biomarker for AMD risk. This study examined the effect of carotenoid supplementation on circulating HDL cholesterol levels. Serum lipid profiles were measured in 20 participants from the Lutein and Zeaxanthin in Pregnancy (L-ZIP) trial, which enrolled 40 pregnant women. In addition to standard prenatal supplements, half received 10 mg of lutein and 2 mg of zeaxanthin daily from the first trimester, and half received a placebo. Carotenoid supplementation significantly increased HDL cholesterol in the third trimester, with no changes in total cholesterol, LDL cholesterol, or triglycerides (TG) across trimesters. To further evaluate individual carotenoids, serum lipids were analyzed in macular pigment transgenic mice fed lutein, zeaxanthin, or β-carotene for one month. All three carotenoids significantly increased HDL cholesterol and reduced TG levels, with the effect ranking as zeaxanthin > lutein > β-carotene. These findings suggest that carotenoid supplementation modulates the serum lipid profile-elevating HDL cholesterol and lowering TG-which may contribute to protection against AMD and other lipid-associated diseases.},
}

@article {pmid41598159,
year = {2025},
author = {Kudasiewicz-Kardaszewska, A and Ozimek, MA and Urbański, T and Jamontt, K and Tkaczenko, A and Bonińska, K and Cisiecki, S},
title = {Combined Pharmacological and Pneumatic Displacement Therapy for Sub-Macular Haemorrhage Secondary to Age-Related Macular Degeneration: A Case Series and Review of the Literature.},
journal = {Life (Basel, Switzerland)},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/life16010003},
pmid = {41598159},
issn = {2075-1729},
abstract = {PURPOSE: We aimed to present the clinical outcomes of a combined pharmacological and gas-assisted treatment for sub-macular haemorrhage secondary to neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective case series included ten eyes with sub-macular haemorrhage (SMH) treated between January 2024 and September 2025. All patients received intravitreal alteplase (100 µg) and C3F8 gas, followed by aflibercept (2 mg or 8 mg) within a treat-and-extend regimen. BCVA- and OCT-based anatomical changes were recorded at baseline, 7-14 days, 1 month, 3 months, and 6 months. BCVA changes were analysed using repeated-measures testing.

RESULTS: Mean BCVA improved from 0.99 ± 0.21 logMAR at baseline to 0.89 ± 0.20 at 7-14 days, 0.80 ± 0.20 at 1 month, 0.60 ± 0.18 at 3 months, and 0.53 ± 0.20 at 6 months (p < 0.05 for overall change). Eight eyes (80 percent) showed restoration of foveal contour, while two developed foveal atrophy. No major adverse events occurred.

CONCLUSION: Combined intravitreal alteplase and C3F8, followed by aflibercept, may provide favourable short-term visual and anatomical improvement in SMH secondary to nAMD. Early intervention appears beneficial, but larger controlled studies are needed to confirm these findings.},
}

@article {pmid41594936,
year = {2026},
author = {Zhang, YY and Sun, QF and Bai, W and Yao, J},
title = {Retinal Astrocytes: Key Coordinators of Developmental Angiogenesis and Neurovascular Homeostasis in Health and Disease.},
journal = {Biology},
volume = {15},
number = {2},
pages = {},
doi = {10.3390/biology15020201},
pmid = {41594936},
issn = {2079-7737},
support = {82271107//National Natural Science Foundation of China/ ; K2023060//Jiangsu Provincial Health Commission Medical Research Key Project/ ; JX10414318//Postgraduate Research and Practice Innovation Program of Jiangsu Province/ ; },
abstract = {Retinal astrocytes reside mainly in the nerve fiber layer and are central to shaping retinal vessels and maintaining neurovascular balance. Derived from the optic nerve head, they spread across the inner retina to form a meshwork that both supports and instructs the emerging superficial vascular plexus. Immature astrocytes supply vascular endothelial growth factor-A(VEGF-A) to guide endothelial sprouting, while signals from growing vessels promote astrocyte maturation and strengthen the blood-retinal barrier. In disorders such as diabetic retinopathy and neovascular age-related macular degeneration, these cells show marked plasticity. Reactive astrogliosis can sustain VEGF and inflammation, favoring fragile, leaky neovessels, whereas alternative astrocyte states help reinforce barrier function and release anti-angiogenic factors. Located at the core of the neurovascular unit, astrocytes communicate continuously with endothelial cells, pericytes and neurons. This review integrates data from single-cell profiling and advanced imaging to outline astrocyte development, morphology and key signaling pathways (VEGF, PDGF, Wnt/Norrin, Eph/ephrin), and considers how tuning astrocyte polarization might be exploited to preserve retinal vascular integrity.},
}

@article {pmid41594154,
year = {2026},
author = {Yoon, T and Kang, D},
title = {Efficient Ensemble Learning with Curriculum-Based Masked Autoencoders for Retinal OCT Classification.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {2},
pages = {},
doi = {10.3390/diagnostics16020179},
pmid = {41594154},
issn = {2075-4418},
support = {RS-2023-00249104//National Research Foundation of Korea (NRF) through a grant funded by the Korean government (MSIT)/ ; },
abstract = {Background/Objectives: Retinal optical coherence tomography (OCT) is essential for diagnosing ocular diseases, yet developing high-performing multiclass classifiers remains challenging due to limited labeled data and the computational cost of self-supervised pretraining. This study aims to address these limitations by introducing a curriculum-based self-supervised framework to improve representation learning and reduce computational burden for OCT classification. Methods: Two ensemble strategies were developed using progressive masked autoencoder (MAE) pretraining. We refer to this curriculum-based MAE framework as CurriMAE (curriculum-based masked autoencoder). CurriMAE-Soup merges multiple curriculum-aware pretrained checkpoints using weight averaging, producing a single model for fine-tuning and inference. CurriMAE-Greedy selects top-performing fine-tuned models from different pretraining stages and ensembles their predictions. Both approaches rely on one curriculum-guided MAE pretraining run, avoiding repeated training with fixed masking ratios. Experiments were conducted on two publicly available retinal OCT datasets, the Kermany dataset for self-supervised pretraining and the OCTDL dataset for downstream evaluation. The OCTDL dataset comprises seven clinically relevant retinal classes, including normal retina, age-related macular degeneration (AMD), diabetic macular edema (DME), epiretinal membrane (ERM), retinal vein occlusion (RVO), retinal artery occlusion (RAO), and vitreomacular interface disease (VID) and the proposed methods were compared against standard MAE variants and supervised baselines including ResNet-34 and ViT-S. Results: Both CurriMAE methods outperformed standard MAE models and supervised baselines. CurriMAE-Greedy achieved the highest performance with an area under the receiver operating characteristic curve (AUC) of 0.995 and accuracy of 93.32%, while CurriMAE-Soup provided competitive accuracy with substantially lower inference complexity. Compared with MAE models trained at fixed masking ratios, the proposed methods improved accuracy while requiring fewer pretraining runs and reduced model storage for inference. Conclusions: The proposed curriculum-based self-supervised ensemble framework offers an effective and resource-efficient solution for multiclass retinal OCT classification. By integrating progressive masking with snapshot-based model fusion, CurriMAE methods provide high performance with reduced computational cost, supporting their potential for real-world ophthalmic imaging applications where labeled data and computational resources are limited.},
}

@article {pmid41593166,
year = {2026},
author = {Lee, JH and Lee, SY and Jang, B and Kim, YG and Yoon, CK and Park, UC and Park, KH and Lee, EK},
title = {OCT biomarkers as predictors of treatment interval in neovascular age-related macular degeneration treated with intravitreal aflibercept using a treat-and-extend regimen.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-36751-4},
pmid = {41593166},
issn = {2045-2322},
}

@article {pmid41592857,
year = {2026},
author = {Wang, Z and Xu, C and Wang, L and Qiang, W and Li, Y and Li, D and Xu, F and Zhang, Y and Jiang, J and Li, Z},
title = {Evaluating reasoning large language models with human-like thinking in ophthalmic question answering.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {1},
pages = {},
doi = {10.1136/bmjophth-2025-002615},
pmid = {41592857},
issn = {2397-3269},
mesh = {Humans ; *Ophthalmology/education ; *Thinking/physiology ; *Language ; *Educational Measurement/methods ; Large Language Models ; },
abstract = {OBJECTIVES: To evaluate the performance of reasoning large language models (LLMs) with human-like thinking in ophthalmic question answering.

METHODS: We evaluated two state-of-the-art open-source reasoning LLMs (DeepSeek-R1 and QwQ-32B) and one conventional non-reasoning LLM (LLaMA-3.3-70B-Instruct) models on ophthalmology questions, assessing not only answer accuracy (ACC) but also the quality of their reasoning processes. First, we curated MedQA-Eye, a dataset of 967 ophthalmology questions across 10 subspecialties, 3 scenarios, 5 medical entities and 3 languages. Second, we proposed a novel framework considering human thinking patterns essential to medical practice to evaluate the thinking performance of reasoning LLMs on MedQA-Eye.

RESULTS: DeepSeek-R1 demonstrated superior overall ACC (90.59%, 95% CI 88.59% to 92.27%) to LLaMA-3.3-70B-Instruct (87.90%, 95% CI 85.69% to 89.81%, p=0.015) and QwQ-32B (84.28%, 95% CI 81.85% to 86.44%, p<0.001) with performance varying across subspecialties. Analysis of reasoning LLMs revealed incorrect logical inference as the primary point of failure, accounting for 93.41%-94.74% of incorrectly answered questions. We further quantified semantic uncertainty in reasoning LLM thinking as a predictor of answer reliability. DeepSeek-R1 exhibited lower semantic uncertainty (1.04±3.63) compared with QwQ-32B (4.31±40.70), p<0.001.

CONCLUSION: Reasoning LLMs demonstrated superior performance in ophthalmology question answering, with DeepSeek-R1 achieving the highest ACC. Our findings demonstrate that reasoning LLM can better simulate human-like thinking processes compared with conventional non-reasoning LLM, suggesting its potential for more trustworthy LLM systems in ophthalmology.},
}

Humans
*Ophthalmology/education
*Thinking/physiology
*Language
*Educational Measurement/methods
Large Language Models

@article {pmid41591569,
year = {2026},
author = {Heidari, Z and Mirghorbani, M and Abounoori, M and Ebrahimibesheli, K and Tabarestani, M and Khabazkhoob, M and Yousefi, S and Modjtahedi, BS},
title = {Vitreoretinal disease detection using artificial intelligence: a systematic review and meta-analysis.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {77},
pmid = {41591569},
issn = {1573-2630},
mesh = {Humans ; *Artificial Intelligence ; *Retinal Diseases/diagnosis ; *Vitreous Body/diagnostic imaging/pathology ; },
abstract = {INTRODUCTION: Early detection of vitreoretinal diseases (VRDs) is critical for preventing vision loss, and currently relies on the examination and interpretation of multimodal imaging techniques. Artificial intelligence (AI) is emerging as a powerful tool to detect abnormalities in vitreoretinal morphology and ideally detect changes at earlier stages to allow for intervention. This meta-analysis evaluates and summarizes the diagnostic performance of AI models in the detection of VRDs using retinal imaging systems.

METHODS: This study was registered in PROSPERO (CRD42023450207). A comprehensive electronic search of PubMed/MEDLINE, EMBASE, and Web of Science was conducted by three independent reviewers up to August 2023. Study validity was assessed using the QUADAS-2 tool, which evaluates risk of bias across four domains and applicability concerns across three domains. Eligible articles were categorized into nine VRD subgroups-age related macular degeneration, diabetic retinopathy, retinal vascular diseases, retinal dystrophies, Cystoid macular edema, vitreoretinal interface disorders, retinal detachment, Central serous chorioretinopathy, and myopic retinopathy-and included in the meta-analysis. Pooled estimates of accuracy (PEA), sensitivity (PESen), and specificity (PESpe) were calculated for all selected studies.

RESULTS: A total of 195 studies were included in the final analysis, yielding an overall PEA of 95.76% (95% CI: 95.0-96.47), PESen of 91.94% (95% CI: 90.72-93.08) and PESpe of 96.09% (95% CI: 95.27-96.79). In the subgroup analysis, most AI models had a PEA > 90%, especially convolutional neural networks (CNN), followed by support vector machine (SVM) and random forest (RF).

CONCLUSIONS: AI diagnostic tools, particularly CNNs, have demonstrated robust performance in VRDs detection. However, results from studies with limited generalizability should be applied cautiously in real-world settings. Further exploration of emerging models, such as large language models (LLMs), is recommended.},
}

Humans
*Artificial Intelligence
*Retinal Diseases/diagnosis
*Vitreous Body/diagnostic imaging/pathology

@article {pmid41590921,
year = {2026},
author = {Lopukhova, EA and Idrisova, GM and Mukhamadeev, TR and Voronkov, GS and Kutluyarov, RV and Topolskaya, EP},
title = {A Hierarchical Deep Learning Architecture for Diagnosing Retinal Diseases Using Cross-Modal OCT to Fundus Translation in the Lack of Paired Data.},
journal = {Journal of imaging},
volume = {12},
number = {1},
pages = {},
doi = {10.3390/jimaging12010036},
pmid = {41590921},
issn = {2313-433X},
abstract = {The paper focuses on automated diagnosis of retinal diseases, particularly Age-related Macular Degeneration (AMD) and diabetic retinopathy (DR), using optical coherence tomography (OCT), while addressing three key challenges: disease comorbidity, severe class imbalance, and the lack of strictly paired OCT and fundus data. We propose a hierarchical modular deep learning system designed for multi-label OCT screening with conditional routing to specialized staging modules. To enable DR staging when fundus images are unavailable, we use cross-modal alignment between OCT and fundus representations. This approach involves training a latent bridge that projects OCT embeddings into the fundus feature space. We enhance clinical reliability through per-class threshold calibration and implement quality control checks for OCT-only DR staging. Experiments demonstrate robust multi-label performance (macro-F1 =0.989±0.006 after per-class threshold calibration) and reliable calibration (ECE =2.1±0.4%), and OCT-only DR staging is feasible in 96.1% of cases that meet the quality control criterion.},
}

@article {pmid41587655,
year = {2026},
author = {Faurite, C and Michaud, C and Olivier, P and Gallice, M and Chiquet, C and Soler, V and Berry, I and Cottereau, BR and Peyrin, C},
title = {Enhancing peripheral scene recognition through spatial frequency training: Behavioral evidence from macular degeneration and healthy aging.},
journal = {Neuropsychologia},
volume = {223},
number = {},
pages = {109377},
doi = {10.1016/j.neuropsychologia.2026.109377},
pmid = {41587655},
issn = {1873-3514},
abstract = {Macular degeneration (MD) causes central vision loss and leads to long-term reorganization of visual functions. Central vision loss in MD severely reduces access to high spatial frequencies (HSF) that convey fine visual details, while low spatial frequencies (LSF) remain relatively accessible through peripheral vision and may support compensatory processing. This study investigated whether repeated training in categorizing filtered scenes improves peripheral scene recognition by enhancing spatial frequency processing. Ten MD patients and ten age- and gender-matched controls performed a scene categorization task (indoor vs. outdoor) using LSF or HSF images. Both groups completed a 12-session training protocol: patients performed the task at their preferred retinal location (PRL), and controls fixated with their fovea and viewed stimuli through an individualized artificial scotoma matched to their paired patient. Before training, MD patients showed a marked deficit for HSF scenes compared to controls, and a milder deficit for LSF scenes. After training, patients exhibited a significant improvement in categorizing LSF scenes, and an improvement specifically limited to HSF outdoor scenes, suggesting enhanced use of preserved peripheral information and partial compensation for the HSF deficit. Older controls also showed reduced performance for HSF scenes in peripheral vision, and similarly benefited from training. These results highlight the potential of perceptual training to enhance peripheral visual processing in MD patients, particularly by leveraging coarse visual cues. They support the idea that such protocols may be beneficial not only for visual rehabilitation in MD but also for preserving visual-cognitive functions in normal aging.},
}

@article {pmid41587414,
year = {2026},
author = {Ramulu, S and Sindal, MD and Thotakura, M and Vaidya, MV and Venkatesh, R and Ramulu, PY},
title = {Patients with age-related macular degeneration face impairment in activities of daily living.},
journal = {Clinical & experimental optometry},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/08164622.2026.2616034},
pmid = {41587414},
issn = {1444-0938},
abstract = {CLINICAL RELEVANCE: Age-related macular degeneration can lead to significant visual impairment in older individuals. These can significantly impact their day-to-day life, and understanding these limitations is crucial for healthcare providers.

BACKGROUND: The aim of this work is to determine impairment of activities of daily living secondary to visual impairment caused by age-related macular degeneration in a South Indian population.

METHODS: In this prospective cross-sectional study, the instrumental activities of daily living questionnaire was administered to participants with uniocular or binocular visual impairment due to age-related macular degeneration, and controls who did not have any significant ocular or retinal pathology.

RESULTS: The study recruited 90 participants in each arm, where those with age-related macular degeneration were older. More participants with age-related macular degeneration (92.2%) had impairment with one or more activities of daily living as compared to controls (55.6%,p < 0.001). The age-related macular degeneration group faced a median of 4 (IQR 2-8) impairments and could perform 53.3% with difficulty, 39.4% with assistance and 7.3% activities could not be completed. In the age-related macular degeneration group, those with unilateral disease had 8.95-fold (p < 0.001) greater level of impairment, while those with bilateral disease has a 10.72-fold (p = 0.001) greater level of impairment as compared to controls.

CONCLUSION: Visual impairment due to age-related macular degeneration has a significant impact on activities of daily living. The patients often need assistance in completing their activities. Care in age-related macular degeneration needs to involve rehabilitation and help in carrying out daily activities in addition to treatment for visual benefits.},
}

@article {pmid41585411,
year = {2026},
author = {Sun, Y and Huang, J and Zhang, Z and Chen, Z and Li, Z and Wu, F and Wang, Z and Wu, T and Yi, G and Meng, F and Wu, S},
title = {Protective Effects of Bone Mineral Density on Age-Related Macular Degeneration: A Mendelian Randomization Study.},
journal = {International journal of endocrinology},
volume = {2026},
number = {},
pages = {6619808},
pmid = {41585411},
issn = {1687-8337},
abstract = {INTRODUCTION: Observational studies have established the connection between a decrease in bone mineral density (BMD) and an increased susceptibility to age-related macular degeneration (AMD). However, the cause-and-effect link of this correlation remains uncertain. This study employed Mendelian randomization (MR) methods to examine the causality between BMDs and AMD.

MATERIALS AND METHODS: The GEnetic Factors for OSteoporosis (GEFOS) Consortium, UK Biobank, and FinnGen Biobank offered summary statistics for BMD and AMD. We adopted an array of quality control procedures to screen for eligible instrumental single nucleotide polymorphisms (SNPs). The inverse variance weighting (IVW) algorithm was the most trustworthy approach in MR analyses. Furthermore, we employed additional analytical methods such as MR-Egger and weighted median (WM) for confirming the soundness of the present MR outcomes.

RESULTS: The findings indicated that genetically predicted total body BMD (TB-BMD, IVW: OR = 0.772, 95% CI = 0.642-0.928, p = 0.006), lumbar spine BMD (LS-BMD, IVW: OR = 0.739, 95% CI = 0.583-0.937, p = 0.013), femoral neck (FN-BMD, WM: OR = 0.626, 95% CI = 0.432-0.906, p = 0.013), and TB-BMD (age over 60, MR-Egger, OR = 0.383, 95% CI = 0.163-0.902, p = 0.041) were associated with lower odds of wet AMD. No significant causal relationship can be found between other BMDs and Wet-AMD, or between BMDs and Dry-AMD.

CONCLUSION: Our MR analysis supported the causal correlation between genetically predicted BMD and Wet-AMD. As to Dry-AMD, it was not causally related to BMD. Our study complemented the evidence from previous observational surveys and emphasized the extraordinary importance of monitoring BMD for preventing and treating AMD.},
}

@article {pmid41584098,
year = {2026},
author = {Weng, CY and Blinder, KJ and Hall, EF and Rosenthal, WN},
title = {Personalizing Personalized Medicine: The Pursuit of Optimal Thresholds in the Home OCT Artificial Intelligence Algorithm for Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {101017},
pmid = {41584098},
issn = {2666-9145},
}

@article {pmid41584096,
year = {2026},
author = {Chakravarthy, U and Csincsik, L and Teo, KYC and Munk, MR and Grewal, DS and Guymer, RH and Jaffe, GJ and Peto, T and Sadda, SR and Staurenghi, G and Cheung, CMG and , },
title = {Standardization of Imaging Criteria for Detecting Macular Fibrosis in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {101027},
pmid = {41584096},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate conventional imaging modalities for detecting fibrosis in neovascular age-related macular degeneration (nAMD) and to develop a standardized diagnostic workflow.

DESIGN: Systematic discussion and grading exercise assessing multiple imaging modalities.

PARTICIPANTS: Retina specialists from the International Fibrosis Consensus workgroup and members of the International Retinal Imaging Society.

METHODS: An international panel assessed the advantages and limitations of 5 imaging modalities-color fundus photography (CFP), fluorescein angiography (FA), spectral domain OCT (SD-OCT), near-infrared reflectance, and fundus autofluorescence-for detecting fibrosis in nAMD. A structured debate was followed by 2 online, masked image grading surveys. Sensitivity, specificity, and predictive accuracy of each modality, alone and in combination, were determined. Intergrader agreement was calculated. Imaging features were also correlated with histology in a nonhuman primate laser model. Based on consensus discussions at 2 in-person meetings and survey results, a 2-step diagnostic approach using SD-OCT as the primary modality was proposed.

MAIN OUTCOME MEASURES: Recommendation for a standardized approach for diagnosing fibrosis in eyes with nAMD.

RESULTS: Among the 5 modalities, SD-OCT was considered essential by all workgroup members. Hyperreflective material on OCT was unanimously identified as a key indicator of fibrosis. However, its limited specificity was acknowledged. In 2 masked grading exercises, SD-OCT showed the highest sensitivity (0.88 and 0.84) but only moderate specificity (0.56 and 0.57). The area under the curve (AUC) for SD-OCT was 0.72 and 0.70. A 2-step strategy combining SD-OCT with CFP or FA improved diagnostic accuracy. Hyperreflective material was defined as material with reflectivity equal to or greater than normal retinal pigment epithelium (RPE), well-defined margins, RPE disruption, and a laminated appearance. Corresponding CFP findings included well-defined yellow/white/gray subretinal lesions, and FA findings included early blocked fluorescence and late staining. This 2-step approach increased AUC to 0.85, with sensitivity of 0.83 and specificity of 0.87.

CONCLUSIONS: The study establishes a 2-step approach using OCT as the primary modality in clinical studies for the detection of fibrosis.

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

@article {pmid41584094,
year = {2026},
author = {Hunt, PW and Olshen, AB and Murad, N and Ambayec, GC and Sezgin, E and Schneider, MF and Jabs, DA},
title = {Erratum to "Plasma Proteomic Markers of Interleukin-1β Pathway Associated with Incident Age-Related Macular Degeneration in Persons with AIDS" [Ophthalmol Sci. 2025;5:100794].},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {100974},
doi = {10.1016/j.xops.2025.100974},
pmid = {41584094},
issn = {2666-9145},
abstract = {[This corrects the article DOI: 10.1016/j.xops.2025.100794.].},
}

@article {pmid41582411,
year = {2026},
author = {},
title = {Highlighting Eye Health for National Age-Related Macular Degeneration Awareness Month.},
journal = {Nursing},
volume = {56},
number = {2},
pages = {63},
doi = {10.1097/NSG.0000000000000329},
pmid = {41582411},
issn = {1538-8689},
}

@article {pmid41582270,
year = {2026},
author = {Fukuda, Y and Sakurada, Y and Kotoda, Y and Kikushima, W and Kashiwagi, K},
title = {Two year outcomes of as needed brolucizumab therapy in exudative age related macular degeneration with or without pachychoroid phenotype.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-37591-y},
pmid = {41582270},
issn = {2045-2322},
abstract = {Brolucizumab is a second-generation vascular endothelial growth factor (VEGF) inhibitor. To date, there have been no reports comparing treatment outcomes between exudative age-related macular degeneration with or without the pachychoroid phenotype using a second-generation VEGF inhibitor. The present study compared two-year as-needed brolucizumab treatment outcomes in patients with and without pachychoroid phenotypes. Sixty-six eyes completed two years of follow-up, and 14 and 52 eyes were classified into the pachychoroid and non-pachychoroid phenotypes, respectively. At 24 months, best-corrected visual acuity (BCVA) significantly improved in both groups, from 0.30 ± 0.29 to 0.12 ± 0.21 in the pachychoroid phenotype and 0.43 ± 0.36 to 0.31 ± 0.37 in the non-pachychoroid phenotype (p = 0.014 and 0.0013, respectively). At the 24-month follow-up, there were significantly fewer eyes requiring retreatment in the pachychoroid phenotype than in the non-pachychoroid phenotype (50% vs. 83%, p = 0.03). Although the number of additional injections was comparable between the two groups in the first 12 months (1.2 ± 1.4 vs. 1.7 ± 1.6, p = 0.29), the number of additional injections was significantly lower in the pachychoroid phenotype than in the non-pachychoroid phenotype (1.5 ± 2.4 vs. 3.2 ± 2.6, p = 0.0098) in the second 12 months. In the 24-month as-needed brolucizumab treatment group, the response to the pachychoroid phenotype was favorable, with significant BCVA improvement and fewer additional injections, particularly in the second 12 months.},
}

@article {pmid41582115,
year = {2026},
author = {Kose, H and Ozkan, B and Kanli, A and Karabas, LV and Akpinar, G and Kasap, M and Sumer, F},
title = {Correction: Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.},
journal = {BMC geriatrics},
volume = {26},
number = {1},
pages = {100},
pmid = {41582115},
issn = {1471-2318},
}

@article {pmid41582022,
year = {2026},
author = {Wang, L and Liu, H and Liu, C},
title = {Comment on "A deep learning approach for the screening of referable age-related macular degeneration - Model development and external validation".},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.01.049},
pmid = {41582022},
issn = {0929-6646},
}

@article {pmid41581636,
year = {2026},
author = {Wu, F and Xu, K and Zhao, Y and Wang, W and Yang, H and Li, Y and Zheng, G and Li, Z and Xia, Y and Liu, Y and Wu, H and Bai, S},
title = {Associations of cardiovascular-kidney-metabolic syndrome with age-related macular degeneration risk.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.01.023},
pmid = {41581636},
issn = {1879-1891},
abstract = {PURPOSE: No study has explored the longitudinal association between cardiovascular-kidney-metabolic (CKM) syndrome and age-related macular degeneration (AMD). We aimed to investigate the associations between CKM syndrome, genetic predisposition, and AMD risk.

DESIGN: Retrospective cohort study.

PARTICIPANTS: A total of 319,638 participants from the UK Biobank who did not have AMD at baseline.

METHODS: CKM syndrome was diagnosed based on the presence of chronic kidney disease, cardiovascular disease, and metabolic risk factors. We categorized participants into stage 0-4 according to their CKM syndrome status. A genetic risk score was used to estimate genetic predisposition to AMD. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AMD.

MAIN OUTCOME MEASURES: AMD incidence.

RESULTS: During a median follow-up of 12.5 years, 4,982 AMD cases were identified. After multivariable adjustment, the HRs (95% CIs) for AMD were 1.15 (1.02-1.30), 1.25 (1.13-1.38), 1.22 (1.08-1.38), and 1.48 (1.30-1.68) for participants in CKM stage 1, 2, 3, and 4, respectively, compared to those in CKM stage 0. No significant interaction between genetic predisposition and CKM syndrome was observed (P for interaction = 0.06). Joint analyses showed that compared to those with CKM stage 0 and low genetic predisposition, individuals with CKM stage 4 and high genetic predisposition, exhibited the highest risk of AMD (HR = 2.67, 95% CI: 2.22-3.33).

CONCLUSIONS: Poor CKM health was positively associated with AMD risk, independent of genetic predisposition.},
}

@article {pmid41581044,
year = {2026},
author = {Ranga, D and Kaur, S and Nallabelli, N and Sharma, SP and Tigari, B and Dogra, M and Katoch, D and Sharma, SK and Singh, R and Singh, N},
title = {Impact of age-related maculopathy susceptibility 2, high-temperature requirement A serine peptidase 1, and complement factor H genetic variants on clinical phenotypes of age-related macular degeneration.},
journal = {Indian journal of ophthalmology},
volume = {74},
number = {2},
pages = {279-285},
doi = {10.4103/IJO.IJO_1395_25},
pmid = {41581044},
issn = {1998-3689},
mesh = {Humans ; *High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism ; *Complement Factor H/genetics/metabolism ; Male ; Female ; *Polymorphism, Single Nucleotide ; Tomography, Optical Coherence ; Aged ; Phenotype ; *Macular Degeneration/genetics/diagnosis/epidemiology/metabolism ; Fluorescein Angiography ; Genotype ; *Proteins/genetics/metabolism ; India/epidemiology ; Middle Aged ; *Genetic Predisposition to Disease ; *DNA/genetics ; Fundus Oculi ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. This study investigated the association of single-nucleotide polymorphisms (SNPs) in ARMS2, HTRA1, and CFH with AMD and its clinical phenotypes and systemic cytokine profiles in a North Indian population.

METHOD: A total of 113 AMD patients and 99 controls were genotyped using TaqMan assays. All patients underwent detailed ophthalmic evaluations, including optical coherence tomography (OCT), fundus photography, and angiography-based imaging. Serum cytokine levels were quantified using bead-based multiplex immunoassay and analyzed via flow cytometry. Statistical analyses were performed using SPSS v23.0, employing t-tests, ANOVA, and Mann-Whitney U tests.

RESULTS: Significant associations were observed between AMD and control for risk alleles in ARMS2 (36.3% vs 10.1%, P = 0.001), HTRA1 (37.2% vs 33.3%, P = 0.003), and CFH (27.4% vs 13.1%, P = 0.001). Genotype-phenotype correlations revealed that heterozygous and homozygous risk genotypes were significantly associated with hallmark AMD features such as pigment epithelial detachment (PED), choroidal neovascular membrane (CNVM), large drusen, and retinal pigment epithelium (RPE) atrophy. Cytokine profiling showed significantly reduced levels of erythropoietin (EPO) in AMD patients and granulocyte colony-stimulating factor (G-CSF) in controls (P = 0.044 and P = 0.023).

CONCLUSION: This study establishes novel genotype-phenotype correlations for ARMS2, HTRA1, and CFH SNPs in a North Indian cohort, linking heterozygous/homozygous risk alleles to distinct AMD clinical features. Reduced EPO and G-CSF levels suggest impaired neuroprotective/anti-inflammatory mechanisms, revealing dual pathways in AMD pathogenesis. By integrating these findings with global data, future efforts can deepen our understanding of AMD's complex etiology and improve patient outcomes worldwide.},
}

Humans
*High-Temperature Requirement A Serine Peptidase 1/genetics/metabolism
*Complement Factor H/genetics/metabolism
Male
Female
*Polymorphism, Single Nucleotide
Tomography, Optical Coherence
Aged
Phenotype
*Macular Degeneration/genetics/diagnosis/epidemiology/metabolism
Fluorescein Angiography
Genotype
*Proteins/genetics/metabolism
India/epidemiology
Middle Aged
*Genetic Predisposition to Disease
*DNA/genetics
Fundus Oculi

@article {pmid41578358,
year = {2026},
author = {Pellegrini, M and Adamo, GG and Cartabellotta, A and Talli, PM and Crisafulli, S and Parmeggiani, F and Mura, M},
title = {Add-on implantation of the smaller-incision new generation implantable miniature telescope (SING IMT™) in pseudophakic eyes.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00797-9},
pmid = {41578358},
issn = {2056-9920},
}

@article {pmid41578078,
year = {2026},
author = {Bansal, M and Singh, P and Mehta, RK and Laul, RS and Rana, P and Shah, U and Vohra, R and Desai, S and Bhomaj, S and Patwardhan, S and Manoher, JM and Sapar, A and Parwal, S and Amabde, AK and Shroff, R and Natesh, S and Biswas, RK and D, LR and Sinha, BP and C K, M and Patel, E and Kamble, A and Bhende, P and Patil, S and Shah, A and Narula, R and Kumari, B and Bathula, L and Kirtane, S and Darji, B and Doshi, M and Parmar, D},
title = {A Phase III Randomized Trial Comparing Efficacy, Safety, and Immunogenicity of ZRC-3285 vs. Eylea[®] in Patients with Wet Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41578078},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aims to evaluate the efficacy, safety, and immunogenicity of ZRC-3285 (aflibercept biosimilar) with Eylea[®] (aflibercept) in patients with neovascular (wet) age-related macular degeneration (nAMD).

METHODS: This phase III, multicenter, double-blind study was conducted across 27 sites in India and randomized (2:1) patients with nAMD into either the test aflibercept (ZRC-3285, Zydus Lifesciences Ltd.) or Eylea[®] (Regeneron Pharmaceuticals, Inc.) groups. All 184 enrolled patients (122 and 62 in the ZRC-3285 and Eylea[®] groups, respectively) were included in the modified intend-to-treat (mITT) population. ZRC-3285 or Eylea[®] was administered by intravitreal injection at a dose of 2 mg (0.05 mL) on days 1, 29, and 57. The primary objective was to assess non-inferiority of ZRC-3285 versus Eylea[®] in treating nAMD and was evaluated by determining the proportion of patients who lose fewer than 15 letters from baseline visual acuity over 12 weeks using the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Secondary objectives included comparison of additional efficacy outcomes, immunogenicity, and safety.

RESULTS: Over 12 weeks, all patients in the ZRC-3285 (122, 100%) and Eylea[®] (62, 100%) groups showed loss of fewer than 15 letters, demonstrating non-inferiority [95% confidence interval (CI) not evaluable (NE); p = NE)] of ZRC-3285 to Eylea[®]. The proportion of patients who gained more than 15 letters in best corrected visual acuity (BCVA) over 12 weeks and the mean changes in BCVA, choroidal neovascularization (CNV), and central retinal thickness (CRT) were similar in both arms.

CONCLUSION: Efficacy, immunogenicity, and safety profiles of ZRC-3285 were found to be similar to those of Eylea[®].

TRIAL REGISTRATION: Clinical trial Registry of India (CTRI): CTRI/2023/09/057655 [Registered on 14/09/2023].},
}

@article {pmid41577331,
year = {2026},
author = {Chung, YC and Alhelaly, M and Nittala, MG and Velaga, SB and He, Y and Haines, JL and Pericak-Vance, MA and Stambolian, D and Sadda, SR},
title = {Optical Coherence Tomography Risk Factors for Progression to Late-Stage Age-related Macular Degeneration in the Amish Eye Study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.01.010},
pmid = {41577331},
issn = {2468-6530},
abstract = {PURPOSE: To characterize the prevalence of some critical optical coherence tomography (OCT) biomarkers-including cuticular drusen and acquired vitelliform lesions (AVLs)-and to identify their relative risk for progression to late age-related macular degeneration (AMD) over two years in subjects with early or intermediate AMD in the Amish Eye Study.

DESIGN: Prospective, observational, longitudinal, population-based cohort study.

PARTICIPANTS: This study included 276 eyes from 171 subjects with early or intermediate AMD at baseline who completed the two-year follow-up.

METHODS: Baseline OCT scans were evaluated for the presence of: cuticular drusen, AVLs, subretinal drusenoid deposits (SDD), high drusen volume (defined as ≥0.2mm[3] within the central 5mm), intraretinal hyperreflective foci (IHRF), hyporeflective drusen cores (hDC), thick/thin double-layer sign, and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). Subfoveal choroidal thickness (SFCT) was also measured.

MAIN OUTCOME MEASURES: Incidence of late AMD (geographic atrophy or macular neovascularization) at two years as determined by multimodal imaging (OCT, color fundus photography (CFP), and confocal fundus autofluorescence (FAF)).

RESULTS: By 2-years of follow-up, 26 eyes (10.7%) progressed to late AMD. The most prevalent baseline features in this cohort, in descending order, were cuticular drusen (52.3%), IHRF (17.3%), hDC (16.0%), thin DLS (11.9%), SDD (8.2%), iRORA (7.8%), AVL (7.0%), and high drusen volume (2.5%). The mean SFCT was 243.23 ± 75.45 μm. Univariate analysis demonstrated that the presence of thick DLS, iRORA, AVL, SDD, IHRF, hDC, and SFCT were associated with increased risk of progression. In multivariate regression, however, only the presence of iRORA (OR: 29.60; 95% CI: 6.86-127.84; p < 0.001) and AVL (OR: 15.90; 95% CI: 3.24-78.00; p < 0.001) remained significant, while the presence of IHRF showed borderline significance (OR: 4.71; 95% CI: 1.00-22.16; p = 0.050).

CONCLUSIONS: In this cohort, the presence of iRORA and AVL was independently associated with progression to late AMD over 2 years. Although cuticular drusen were highly prevalent, their presence, as assessed in this study, was not significantly associated with an increased risk of progression to late AMD.},
}

@article {pmid41577329,
year = {2026},
author = {Lee, J and Han, M and Wang, K and Butler, LR and Sinclair, DA},
title = {Epigenetic Reprogramming for Ocular Aging and Disease: Mechanisms, Biomarkers, and the Road to the Clinic.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101442},
doi = {10.1016/j.preteyeres.2026.101442},
pmid = {41577329},
issn = {1873-1635},
abstract = {The eye's visual function relies on retinal neural cells that are long-lived, post-mitotic, and possess minimal regenerative capacity. These combined properties render them exceptionally vulnerable to the cumulative damage that drives age-related functional decline. Accumulating evidence now implicates epigenetic alterations, such as aberrant DNA methylation and histone modifications, not merely as correlates of aging but as fundamental drivers of aging and disease. These changes disrupt the stable gene expression programs required to maintain cellular identity and function, thereby contributing to the pathogenesis of irreversible blinding diseases like glaucoma and age-related macular degeneration (AMD). Unlike immutable genetic mutations, the reversible nature of these epigenetic marks offers a novel therapeutic paradigm. Epigenetic reprogramming, a strategy involving the transient expression of Yamanaka factors or chemical cocktails, provides a powerful means to reset this dysregulated epigenetic landscape and restore cells to a more youthful state. Compelling preclinical studies have validated this approach by demonstrating vision restoration in models of optic neuropathy through the rejuvenation of damaged and aged neurons. This review provides a comprehensive overview of ocular aging from an epigenetic perspective, examines the promise and potential concerns of epigenetic reprogramming, and discusses the future of rejuvenation therapies in ophthalmology.},
}

@article {pmid41576663,
year = {2026},
author = {Liu, W and Wang, L and Jiang, S},
title = {FGF21 protects retinal pigment epithelium from sodium iodate-induced injury: Association with inhibition of ferroptosis and the NRF2/GPX4 pathway.},
journal = {Experimental eye research},
volume = {265},
number = {},
pages = {110883},
doi = {10.1016/j.exer.2026.110883},
pmid = {41576663},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness, with retinal pigment epithelium (RPE) cell death representing a central pathological event. Ferroptosis, an iron-dependent form of regulated cell death, has recently been implicated in RPE degeneration. Although fibroblast growth factor 21 (FGF21) has demonstrated cytoprotective effects in various contexts, its specific role and mechanism in RPE protection, particularly concerning ferroptosis, remain unexplored. This study investigated the protective effect of FGF21 against sodium iodate (NaIO3)-induced damage and its underlying mechanism, with a focus on ferroptosis. In vitro, NaIO3 treatment induced significant injury in ARPE-19 cells, which was effectively rescued by FGF21 co-treatment. The protective efficacy of FGF21 was comparable to that of the specific ferroptosis inhibitor Ferrostatin-1. Mechanistically, FGF21 alleviated intracellular iron overload in ARPE-19 cells by modulating the expression of iron regulators (CD71 and FPN1), reduced lipid peroxidation, and restored glutathione levels. Mechanistic exploration revealed that FGF21 treatment was associated with the upregulation of NRF2 and HO-1 and, crucially, with the attenuation of GPX4 downregulation. In a NaIO3-induced mouse model of retinal degeneration, FGF21 administration significantly preserved retinal structure, as evidenced by the maintained outer nuclear layer and total retinal thickness in optical coherence tomography (OCT) and histological analyses. Consistent with the cellular findings, FGF21 upregulated GPX4, NRF2, and HO-1 protein expression in retinal tissues. Our findings demonstrate that FGF21 protects ARPE-19 cells and the retina from NaIO3-induced damage. Its protective profile is closely associated with the mitigation of key ferroptosis hallmarks and correlates with the modulation of the NRF2/GPX4 antioxidant axis. This study provides novel insights and important preclinical evidence supporting further investigation into FGF21 as a potential therapeutic agent for ferroptosis-related retinal degenerative diseases.},
}

@article {pmid41573440,
year = {2025},
author = {Mangrio, SM and Faisal, S and Malik, Z and Naeem, A and Saeed, U},
title = {Unilateral Ptosis and Bulbar Symptoms as the Initial Presentation of Late-Onset Acetylcholine Receptor Antibody-Positive Myasthenia Gravis Mimicking Acute Ischemic Stroke in an 82-Year-Old Man.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99832},
pmid = {41573440},
issn = {2168-8184},
abstract = {Myasthenia gravis is an autoimmune disorder of the neuromuscular junction. In older adults, it may present with bulbar and ocular symptoms that resemble acute stroke. Ocular myasthenia is typically asymmetric and often bilateral; persistent unilateral ptosis in this context can be misleading. An 82-year-old man with type 2 diabetes mellitus, chronic kidney disease, cataracts, and macular degeneration presented with a two-week history of fatigable dysphagia, slurred speech, and new-onset unilateral left ptosis. Symptoms were worse towards the end of the day. He denied diplopia and limb weakness. On examination, he was alert with marked left ptosis, mild left facial weakness, and normal limb strength and gait. A working diagnosis of ischemic stroke was made. Computed tomography of the head, magnetic resonance imaging of the brain with magnetic resonance angiography, and carotid Doppler ultrasound showed no acute vascular pathology. Speech and language therapy assessment demonstrated moderately dysarthric but functional speech and a safe swallow using compensatory strategies. ENT review was arranged as a safety assessment to exclude structural lesions or throat pathology in view of his recent swallowing difficulty, sensation of food sticking on the left side, and intermittent nasal speech later in the day; flexible nasal endoscopy was normal. Neurology review noted fluctuating bulbar symptoms with isolated unilateral ptosis, normal extraocular movements, and a normal limb examination, raising suspicion for myasthenia gravis. Pyridostigmine was started with rapid improvement in ptosis, speech, and swallowing. By the following day, both eyes were open, and he was seen reading, although transient recurrence of ptosis was observed during reassessment, consistent with fatiguability. Computed tomography of the chest excluded thymoma. During brief withdrawal of pyridostigmine for neurophysiology, unilateral ptosis and dysphagia recurred. Nerve conduction studies and limited single-fibre electromyography were non-diagnostic. Subsequent serology confirmed positive acetylcholine receptor antibodies (13.8) and negative anti-MuSK antibodies. He was treated with pyridostigmine and oral prednisolone with gastric and bone protection and close monitoring of glycaemic control. At follow-up, he remained asymptomatic, with full resolution of unilateral ptosis and bulbar symptoms. Persistent unilateral ptosis with fluctuating bulbar symptoms in an elderly patient, normal neuroimaging, and preserved limb strength should prompt consideration of myasthenia gravis despite an initial stroke pathway. As most cases classically present before the age of 50-60 years, this presentation in an 82-year-old man also illustrates very late-onset acetylcholine receptor antibody-positive disease. This case highlights that unilateral ocular involvement does not exclude myasthenia gravis and that close attention to fatigability and symptom evolution can prevent misdiagnosis and support timely, appropriate treatment.},
}