@article {pmid41732606,
year = {2026},
author = {Ladki, M and Gupta, PK and Malaya, L and Afrouzian, M},
title = {Dry Age-Related Macular Degeneration and Dense Deposit Disease: A Histopathological Comparison of Macular and Renal Lesions.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e102164},
pmid = {41732606},
issn = {2168-8184},
abstract = {Background Dry age-related macular degeneration (AMD) and dense deposit disease (DDD) in the kidney have molecular commonality due to the involvement of the complement system. DDD is a renal disease linked to defects of the complement alternative pathway, and in dry AMD, complement components have been found within drusen. In this study, pathologic features of dry AMD and DDD were studied by light and immunofluorescence microscopy to clarify whether morphologic similarities exist between the two diseases. Methodology Sections were obtained from (1) the macula of four patients with dry AMD; (2) renal biopsies of two DDD patients; (3) the macula from healthy eye donors; and (4) a kidney biopsy of a normal human subject. Sections were stained with hematoxylin and eosin, periodic acid-Schiff (PAS), and periodic-acid-methenamine silver for light microscopy and with C3b antisera for fluorescence microscopy. Results Changes observed in dry AMD specimens included (1) the presence of numerous drusen containing PAS- and silver-positive material; (2) thickening of the Bruch's membrane; (3) thickening of prominent PAS-positive intercapillary pillars; and (4) degeneration and dropouts in the choriocapillaris and dilatation and congestion of vessels in the Sattler's layer. In comparison, changes in the DDD specimens included (1) thickening of the glomerular basement membrane (GBM) and presence of double contours; and (2) mesangial and endocapillary proliferation. C3b was positive in both macular drusen and along the GBM. Conclusions Basement membrane changes in dry AMD share morphological similarities with the GBM changes in DDD, and, in both diseases, C3b is deposited, suggesting that the association between the two diseases possibly reflects a common pathogenesis.},
}

@article {pmid41731445,
year = {2026},
author = {Seweryn, M and Kopel, J and Augustynska, J and Mikołajewicz, A and Toro, MD and Rejdak, R},
title = {Multidimensional evaluation of the potential impact of faricimab availability on healthcare system accessibility for retinal disease treatment in Poland.},
journal = {BMC health services research},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12913-026-14231-9},
pmid = {41731445},
issn = {1472-6963},
}

@article {pmid41731033,
year = {2026},
author = {Lamanna, F and Riotto, E and Faes, L and Fu, DJ},
title = {Infographic: ranibizumab for neovascular age-related macular degeneration: the MARINA study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41433-026-04348-w},
pmid = {41731033},
issn = {1476-5454},
}

@article {pmid41728315,
year = {2026},
author = {Liu, R and Wang, X and Corradetti, G and Soylu, C and Ferrington, DA and Sadda, SR and Zhang, Y},
title = {Adaptive Optics Fluorescence Lifetime Imaging Ophthalmoscopy for Single-Cell-Resolved In Vivo Metabolic and Structural Imaging of the Human Retinal Pigment Epithelium.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.07.26345814},
pmid = {41728315},
abstract = {Fluorescence lifetime imaging ophthalmoscopy permits in vivo assessment of retinal metabolism but has remained limited by insufficient cellular resolution in the human eye. Here we present adaptive optics-enhanced fluorescence lifetime imaging ophthalmoscopy (AOFLIO), a method for single-cell-resolved, in vivo structural and metabolic imaging of the human retinal pigment epithelium (RPE). Through real-time correction of ocular wavefront aberrations, precisely synchronized adaptive optics reflectance and lifetime image acquisition via a phase-locked loop-based timing architecture, and sub-pixel photon registration that localizes individual autofluorescence photons with high spatial precision, AOFLIO directly resolves the RPE cell mosaic and measures autofluorescence decay using the same photons, enabling direct structural-functional correlation at the single-cell level. We demonstrate single-cell RPE lifetime mapping in healthy subjects and reveal altered metabolic signatures and fine characterization of RPE metabolic in age-related macular degeneration. AOFLIO establishes a platform for cellular-scale metabolic imaging in the living human eye.},
}

@article {pmid41727524,
year = {2026},
author = {Patel, RH and Mothy, D and Boinpally, N and Choudhry, HS and Bhavsar, P and Khouri, AS},
title = {Evaluation of Social Media Short-Form Video Content for Patient Education on Vision-Threatening Diseases.},
journal = {Journal of ophthalmology},
volume = {2026},
number = {},
pages = {8987000},
pmid = {41727524},
issn = {2090-004X},
abstract = {PURPOSE: The rapid spread of unreliable misinformation on vision-threatening diseases can significantly affect the eye health behaviors and outcomes of the patients consuming short-form social media content. This study evaluates short-form videos pertaining to vision-threatening diseases to quantify video quality, content, and popularity.

METHODS: This cross-sectional study analyzed short-form videos on cataracts, diabetic retinopathy, glaucoma, and age-related macular degeneration from TikTok, Instagram Reels, and YouTube Shorts. A hashtag search identified the first fifty videos on each disease from each social media platform. Two reviewers evaluated them, resolving discrepancies with a third. Outcome measures included number of views, likes, comments, uploader source, content type, modified DISCERN score (0-5 scale), and global quality scale (GQS) score (1-5 scale). Engagement outcomes were summarized descriptively using medians and interquartile ranges, while reliability and quality outcomes were analyzed using one-way ANOVA with Tukey post hoc comparisons.

RESULTS: TikTok videos demonstrated higher median engagement (views, likes, and comments) compared to Instagram Reels and YouTube Shorts. Videos on cataracts had higher engagement statistics compared to the other vision-threatening diseases across all platforms. Physicians were the most common video source (45%). The most common content categories were treatments/management (36%) and general symptoms (22%). YouTube Shorts had a significantly greater average DISCERN (2.93 ± 0.70) and GQS score (3.85 ± 1.26) than Instagram Reels and TikTok (p < 0.001). Videos from patients had the lowest mean DISCERN and GQS scores.

CONCLUSIONS: TikTok had the greatest median engagement levels, while YouTube Shorts had the greatest mean quality and reliability. Videos from patients and philanthropists had lower quality scores, while healthcare professionals and organizations had the highest. Future efforts should understand the patients' perspectives, address misinformation, and improve quality across all social media platforms.},
}

@article {pmid41727089,
year = {2026},
author = {Lim, RR and Zhao, E and Hass, DT and Wang, Y and Eminhizer, M and Ortolan, D and Niernberger, S and Tong, A and Nelson, BR and Nazario, M and Adipudi, V and Bharti, K and Hurley, JB and Du, J and Chao, JR},
title = {Nutrient microenvironments reprogram RPE metabolism.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.11.705448},
pmid = {41727089},
issn = {2692-8205},
abstract = {Induced pluripotent stem cell-derived retinal pigment epithelium (iPSC RPE) has become a widely used model for studying the mechanisms of age-related macular degeneration (AMD). However, the nutrient composition of currently used RPE culture media is highly variable, posing a major challenge to reproducibility in RPE metabolism and phenotype. We systematically investigate how six distinct nutrient microenvironments shape RPE phenotype, function and metabolism in both iPSC RPE and fetal RPE (fRPE). These included MEMα, DMEM-HG/F12 basal media, physiological human plasma-like medium (HPLM) supplemented with FBS or B27, and X-VIVO 10. Although canonical RPE markers were expressed across all conditions, B27 supplementation and X-VIVO 10 increased RPE cell size, hexagonality, and transepithelial resistance. Culture in HPLM+FBS induced accumulation of lipid droplets and sub-RPE deposits, whereas X-VIVO 10 resulted in the formation of large intracellular vacuoles. B27 supplementation enhanced basal respiration, while X-VIVO 10 increased glycolytic capacity. Amino acid consumption was broadly conserved across media types, including complete depletion of proline in all conditions by 48 hours; however, lipid and nucleotide metabolism varied substantially between conditions. Notably, B27 supplementation in specific media types reversed the net direction of several metabolites, with creatine, serine and taurine shifting from consumption to production, while riboflavin and guanine shifted from production to consumption. These findings establish the nutrient environment as a key determinant of RPE phenotype, function and metabolism. Our work provides a valuable resource for media selection and interpretation of cellular and metabolic phenotypes relevant to RPE disease modeling.},
}

@article {pmid41726370,
year = {2026},
author = {Afarid, M and Baghban, R and Ghasemali, S and Zamani, J and Zareei, A},
title = {In Silico Design and Analysis of a Novel Ranibizumab-derived Peptide against the Vascular Endothelial Growth Factor.},
journal = {Journal of ophthalmic & vision research},
volume = {21},
number = {},
pages = {},
pmid = {41726370},
issn = {2008-2010},
abstract = {PURPOSE: Blocking the interaction between vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) is recognized as an effective strategy for treating neovascular age-related macular degeneration (nAMD). The present research aimed at designing and modelling an anti-VEGF peptide based on ranibizumab for potential application in inhibiting the VEGF/VEGFR2 interaction.

METHODS: Effective amino acids in the interaction between VEGF and ranibizumab were analyzed using Swiss-PdbViewer (SPDBV), PyMOL, and Chimera software. The effective area in this interaction was determined and applied as a basis to design a peptide. Then, this sequence (containing 25 amino acids) was subjected to random mutagenesis, and the binding affinity of the resulting peptides was analyzed using the ClusPro software. Subsequently, GROMACS v5.0.6 was employed for molecular dynamics (MD) simulations to evaluate the stability of target-ligand complexes. Ultimately, the peptide exhibiting the highest affinity was grafted into the kB1 and MCoTI-II frameworks to enhance the stability.

RESULTS: This modification resulted in improved peptide-VEGF binding affinity, demonstrating the potential of in silico design for creating effective anti-angiogenic peptides in antiangiogenic therapies.

CONCLUSION: The findings from this study provide a basis for designing and validating peptide inhibitors against VEGF.},
}

@article {pmid41725834,
year = {2026},
author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Wang, YX and Nangia, V and Panda-Jonas, S},
title = {Differentiation Between Moderate Versus High Myopia: The 2-Continent Eye Study.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {100999},
pmid = {41725834},
issn = {2666-9145},
abstract = {OBJECTIVE: To determine the cutoff value in axial length between moderate myopia versus high myopia in dependence on the prevalence of myopic macular degeneration (MMD).

DESIGN: Population-based studies conducted in Russia, China, and India.

PARTICIPANTS: The project included the population-based investigations of the Beijing Eye Study (n = 3325; age: 40+ years), Russian Ural Eye and Medical Study (n = 5586 participants; age: 40+ years), Ural Very Old Study (n = 541; age: 85+ years) and Ural Children Eye Study (n = 4255; age: 6+ years), and Central India Eye and Medical Study (n = 4467; age: 30+ years).

METHODS: The participants underwent a series of general medical and ophthalmic examinations, including fundus photography and ocular biometry. Myopic macular degeneration was defined according to the Meta-analysis for Pathologic Myopia Study Group.

MAIN OUTCOME MEASURES: Prevalence of MMD in dependence on axial length.

RESULTS: The total study population included 36 123 eyes (18 471 individuals) (age: 47.4 ± 23.4 years; range: 6-100 years) (axial length: 23.2 ± 1.1 mm; range: 18.22-34.20 mm). In the total study population, higher MMD stage was associated with longer axial length (β: 0.55; B: 0.14; 95% confidence interval [CI]: 0.14-0.15; P < 0.001), older age (β: 0.09; B: 0.001; 95% CI: 0.001-0.001; P < 0.001), female sex (β: 0.12; B: 0.07; 95% CI: 0.06-0.07; P < 0.001), and Indian ethnicity (β: 0.10; B: 0.07; 95% CI: 0.06-0.07; P < 0.001). Higher prevalence of MMD stage 2+ and 3+ correlated with longer axial length (odds ratio [OR]: 9.10; 95% CI: 6.93-11.9; P < 0.001 and OR: 6.90; 95% CI: 5.14-9.26; P < 0.001, respectively), older age (OR: 1.06; 95% CI: 1.04-1.08; P < 0.001 and OR: 1.08; 95% CI: 1.05-1.11; P < 0.001, respectively), and Indian ethnicity (OR: 6.96; 95% CI: 2.70-17.9; P < 0.001 and OR: 3.69; 95% CI: 1.26-10.8; P = 0.02, respectively). The turning points of the regression curves of the associations of axial length with prevalence of MMD stage 2+ and 3+ were located at axial length values of between 26.0 and 26.5 mm, respectively.

CONCLUSIONS: The axial length-related cutoff for moderate versus high myopia was located approximately at 26.0 and 26.5 mm for the prevalence of MMD stage 2+ and 3+, respectively, with higher values for younger individuals. Myopic macular degeneration prevalence was higher in the Indian cohort.

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

@article {pmid41724259,
year = {2026},
author = {Han, M and Wei, M and Zhao, J and Yu, Y and Li, J and Li, X and Gou, J and He, H and Tang, X and Kong, J and Yin, T and Zhang, Y},
title = {Butylphthalide nanoemulsion for management of dry age-related macular degeneration via antioxidant and anti-inflammatory mechanisms.},
journal = {International journal of pharmaceutics},
volume = {},
number = {},
pages = {126702},
doi = {10.1016/j.ijpharm.2026.126702},
pmid = {41724259},
issn = {1873-3476},
abstract = {Dry age-related macular degeneration (dry AMD) is a posterior ocular segment disease characterized primarily by progressive retinal pigment epithelium degeneration, which is driven largely by oxidative stress. Effective treatment remains challenging owing to limited therapeutic agents and intrinsic physiological barriers that hinder drug delivery to the posterior eye. To address this, we developed a butylphthalide-loaded nanoemulsion (NBP-NE) that exhibits potent reactive oxygen species-scavenging and anti-inflammatory properties. Ex vivo permeation studies and pharmacokinetic analysis revealed that NBP-NE significantly enhances corneal and scleral penetration of butylphthalide (NBP), suggesting improved posterior ocular delivery. Moreover, NBP-NE exhibited robust antioxidant and anti-inflammatory effects in both in vitro and in vivo models, mechanisms associated with upregulation of the Nrf2 pathway and suppression of NF-κB signaling. In a sodium iodate-induced mouse model of dry AMD, topical administration of NBP-NE provided superior retinal morphological and functional protection by effectively attenuating oxidative stress and inflammatory responses. These findings represent the first reported application of NBP for dry AMD therapy and position NBP-NE as a promising noninvasive strategy for managing other oxidative stress-related posterior ocular diseases.},
}

@article {pmid41723561,
year = {2026},
author = {Wu, L and Rojas, S and Rao, X and Politis, M and Roca, JA and Nehemy, M and Berrocal, MH and Fromow-Guerra, J and Barraza-Lino, K and Lopez, C and Maia, M and Cardenas-Mirón, A and Gabela, G and Baldivieso-Hurtado, O and Gabela, C and Chinchilla, L and Verdaguer, JI and Zas, M and Young, M and García-Aguirre, G and Ramirez-Estudillo, JA and Abreu, N and Flores, M and Velez, W and Baez, Y and Arriola-Lopez, A and Casella, AM},
title = {Early Latin American experience with faricimab for retinal diseases: FARI-LATAM study for the Pan-American collaborative retina study (PACORES) group.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00804-7},
pmid = {41723561},
issn = {2056-9920},
}

@article {pmid41723406,
year = {2026},
author = {Moukhadder, HM and Wahoud, N and Hassan, SA and Saade, JS},
title = {A case report of spontaneously resolving Descemet's detachment after cataract surgery.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {41723406},
issn = {1471-2415},
abstract = {PURPOSE: To report a case of large central Descemet's membrane detachment (DMD) following cataract surgery and discuss the potential for spontaneous resolution as an alternative to surgical intervention.

OBSERVATIONS: A 79-year-old male with a history of macular degeneration and ocular hypertension developed a large central DMD following cataract surgery complicated by posterior capsular rupture. The patient initially presented with severe corneal edema and an uncorrected visual acuity (UCVA) of 20/200. Despite medical treatment, the DMD persisted, and surgical intervention was considered at week 4 post-op. However, the patient was lost to follow-up, and the surgery could not be performed. At a six-week follow-up, the DMD had resolved spontaneously, with the patient's UCVA improving to 20/30 and best-corrected visual acuity (BCVA) to 20/20.

CONCLUSIONS AND IMPORTANCE: This case demonstrates that large central DMDs (Descemet's membrane detachments) can occasionally resolve spontaneously.},
}

@article {pmid41723148,
year = {2026},
author = {Cui, X and Hui, J and Han, Z and Han, Q},
title = {Antioxidant vitamin index and risk of age-related macular degeneration: multicenter validation and clinical translation.},
journal = {npj aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41514-026-00348-y},
pmid = {41723148},
issn = {2731-6068},
support = {NKSGZ202305//Nankai University Eye Institute Key Science and Technology Fund/ ; TJYXZDXK-3-004A-3//Tianjin Key Medical Discipline Construction/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults, with oxidative stress as a central driver. We proposed the Antioxidant Vitamin Index (AVI), a composite indicator integrating vitamins A, C, and E to quantify systemic antioxidant nutritional status, and evaluated its association with AMD across three large cohorts: the UK Biobank, NHANES 2005-2008, and a Tianjin clinical cohort. Using Cox proportional hazards models for incident AMD in the UK Biobank and multivariable logistic regression for AMD prevalence in NHANES and Tianjin, complemented by restricted cubic splines, quartile analyses, and machine learning, we consistently observed that higher AVI was independently associated with a lower risk of AMD. Dose-response analyses showed a progressive decline in AMD risk with increasing AVI, and model performance improved when AVI was added to conventional risk factors. Machine learning and SHAP interpretation further identified age and AVI as dominant predictors of AMD. These findings support AVI as a biologically grounded, quantifiable metric with potential for early screening, risk stratification, and nutrition-based prevention of AMD.},
}

@article {pmid41722793,
year = {2026},
author = {Zhuang, Z and Jia, X and Lin, H and Hu, P and Hu, J},
title = {Bidirectional causal associations between immune cell phenotypes and age-related macular degeneration subtypes: A mendelian randomization study.},
journal = {Experimental gerontology},
volume = {},
number = {},
pages = {113074},
doi = {10.1016/j.exger.2026.113074},
pmid = {41722793},
issn = {1873-6815},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly population, characterized by two primary subtypes: dry AMD (dAMD) and wet AMD (wAMD). While immune mechanisms are implicated in AMD pathogenesis, the causal relationships between specific immune cell phenotypes and AMD subtypes remain incompletely characterized.

METHODS: Bidirectional two-sample Mendelian randomization (MR) analysis was conducted to evaluate causal associations between 731 immune cell phenotypes and AMD subtypes. Immune cell phenotype data were sourced from publicly available GWAS datasets, encompassing 3757 individuals of European descent. AMD data were obtained from the Finnish Finngen R10 database, including 5239 wAMD cases and 6651 dAMD cases. The inverse-variance weighted (IVW) method was used as the primary analytical approach, complemented by reverse MR analysis to assess bidirectional relationships.

RESULTS: The MR analysis identified significant causal associations between specific immune cell phenotypes and AMD subtypes. For wAMD, the expression of HLA-DR on CD14[-]CD16[+] monocytes exhibited a positive association (OR = 1.11, P = 1.65 × 10[-5]), whereas CD25 on CD28[+]CD4[+] T cells showed a negative association (OR = 0.87, P = 0.70 × 10[-4]). In the case of dAMD, the expression of HLA-DR on CD14[+]CD16[+] monocytes was positively associated with disease risk (OR = 1.13, P = 0.84 × 10[-6]). Reverse MR analysis revealed that dAMD negatively influenced the expression levels of Effector Memory CD4[-]CD8[-] T cells (OR = 0.91, P = 0.36 × 10[-4]) and CD28[+]CD4[-]CD8[-] T cells (OR = 0.92, P = 0.90 × 10[-4]). Notably, no evidence supported a causal effect of wAMD on immune cell phenotypes.

CONCLUSIONS: Using updated GWAS data, this study confirms subtype-specific immune associations in AMD and reports the first evidence of reverse causality: dAMD may directly modulates adaptive immune cell phenotypes. These findings refine our understanding of AMD immunopathogenesis and highlight potential targets for subtype-specific therapies.},
}

@article {pmid41721855,
year = {2026},
author = {Borchert, GA and Charbel Issa, P and Xue, K and MacLaren, RE and Cehajic-Kapetanovic, J and Downes, SM and De Silva, SR},
title = {Geographic atrophy in age-related macular degeneration: phenotypic characterisation for clinical trial consideration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41721855},
issn = {1435-702X},
abstract = {Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) and a leading cause of central vision loss. Advances in multimodal imaging for GA have improved its phenotypic characterisation, enabling more precise assessment of disease. This is increasingly important for identifying features predictive of progression to inform prognosis and guide patient counselling, enable selection for clinical trials and for disease monitoring both in routine clinical practice and in a research setting. In addition, accurately determining foveal involvement is crucial for selection of patients suitable for emerging therapies. High-resolution imaging is also important to recognise and distinguish GA subtypes such as pachychoroid GA from conventional GA, given their genetic and phenotypic differences and possible variation in response to therapy.Imaging modalities include colour fundus photography, which is widely available and allows an initial assessment of GA lesions. Fundus autofluorescence imaging permits clear visualisation of GA borders and provides an accurate topographical map of GA pattern and extent, whereas near-infrared reflectance imaging may be superior for evaluation of foveal involvement. Optical coherence tomography (OCT) allows for measurement of the ellipsoid zone which may correlate to visual function and permits differentiation between biomarkers such as nascent GA, incomplete and complete retinal pigment epithelium and outer retinal atrophy (iRORA and cRORA respectively), and identification of pachychoroid GA. Each of these have important prognostic implications and enable accurate selection for clinical trials, monitoring progression and treatment response. Emerging approaches such as red excitation light and high-resolution OCT, may provide more accurate and reliable assessment of atrophic changes. Alongside these advances, artificial intelligence-based tools show great potential in automating GA detection, characterising of structural biomarkers, measuring progression rates and screening patients for clinical trials, increasingly reliability and reproducibility. A better understanding of the important role of multimodal imaging in the classification and assessment of GA, and detection of factors that affect progression will enable clinicians to advise, monitor and, where possible, appropriately treat this major cause of sight loss.},
}

@article {pmid41720710,
year = {2026},
author = {Cupertino, L and Colon, CG and Kang, A and Kolosky, T and Zhou, J and Levin, MR and Alexander, JL},
title = {Accessibility and readability of Spanish and Portuguese-translated online information about common eye conditions: A cross-sectional content analysis study.},
journal = {Journal of the National Medical Association},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jnma.2026.01.005},
pmid = {41720710},
issn = {1943-4693},
abstract = {PURPOSE: To evaluate the readability and accountability (reliability, quality, and credibility) of online patient education materials for common eye conditions in English, Portuguese, and Spanish.

DESIGN: Cross-sectional content analysis SUBJECTS: A total of 192 websites across seven eye diseases were analyzed in three languages: English (n = 63), Portuguese (n = 67), and Spanish (n = 62).

METHODS: First-page Google search websites for macular degeneration, cataract, diabetic retinopathy, glaucoma, conjunctivitis, uveitis, and dry eye were assessed for readability using Flesch-Kincaid Grade Level (FKGL), Gunning Fog Index (GFI), and Flesch Reading Ease (FRE). Accountability was evaluated using JAMA and DISCERN benchmarks. Websites were also categorized by source type into: academic, national, private, or crowdsourced. Statistical analyses were done using MANOVA, ANOVA, and Tukey's HSD post-hoc tests.

MAIN OUTCOME MEASURES: Readability (FKGL, GFI, FRE) and accountability (JAMA, DISCERN) indices RESULTS: English-language websites had significantly more accessible readability scores (mean FKGL 8.1) than Spanish (16.6) and Portuguese (16.0) counterparts (p < 0.001). Portuguese websites had the lowest JAMA scores (1.2) and were predominantly authored by private entities. Spanish-language sites showed mixed results, outperforming English in some accountability metrics. Crowdsourced pages like Wikipedia had the highest accountability but poorest readability. Language was a significant predictor for readability and accountability in a multivariate analysis (p < 0.001).

CONCLUSION: Online ophthalmology patient education materials in Portuguese and Spanish demonstrate significantly poorer readability, and in some cases, lower accountability compared to English-language resources, posing a significant barrier for patients with limited English proficiency. Future efforts should focus on developing standardized, multilingual patient education materials that balance readability with content reliability, potentially incorporating tools such as large language models (LLM's), which have shown potential in improving accessibility of non-English health information.},
}

@article {pmid41720386,
year = {2026},
author = {Yang, X and Xu, W and Xie, H and Guo, X and Zhu, F and Xing, Y and Chen, C},
title = {SREBP1-driven SCD1 protects retinal pigment epithelium from oxidative damage by activating the NRF2/GPX4 axis.},
journal = {Experimental eye research},
volume = {266},
number = {},
pages = {110932},
doi = {10.1016/j.exer.2026.110932},
pmid = {41720386},
issn = {1096-0007},
abstract = {This study reveals the pivotal role of the Sterol Regulatory Element-Binding Protein 1 (SREBP1)/Stearoyl-CoA Desaturase 1 (SCD1) lipid metabolic axis in protecting retinal pigment epithelium (RPE) against oxidative damage. We demonstrate SCD1 downregulation in age-related macular degeneration (AMD) patient tissues and sodium iodate (SI)-induced models, while its overexpression enhances cell viability and ameliorates oxidative injury. Mechanistically, we uncover a novel pathway where SCD1-derived oleic acid activates the nuclear factor erythroid 2-related factor 2 (NRF2)/glutathione peroxidase 4 (GPX4) signaling cascade, scavenging reactive oxygen species (ROS) and suppressing lipid peroxidation. Notably, oleic acid also mitigated oxidative stress via this pathway without directly promoting cell survival. These results not only elucidate SCD1's crucial protective mechanism in AMD pathogenesis but also establish the SREBP1/SCD1 axis as a promising therapeutic target for developing innovative interventions against retinal degeneration.},
}

@article {pmid41720012,
year = {2026},
author = {Li, H and Xiong, Y and Zheng, Y},
title = {Hyperoside as a promising multi-target candidate for neovascular age-related macular degeneration. mechanisms involving Wnt/β-catenin signaling, oxidative stress, and inflammation suppression.},
journal = {Phytomedicine : international journal of phytotherapy and phytopharmacology},
volume = {153},
number = {},
pages = {157952},
doi = {10.1016/j.phymed.2026.157952},
pmid = {41720012},
issn = {1618-095X},
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD), which is primarily characterized by choroidal neovascularization (CNV), encounters limitations with current therapeutic approaches, including treatment resistance and the burden of frequent injections, highlighting the need for exploring novel effective therapeutic agents and their mechanisms for nAMD management. Oxidative stress and inflammation are core pathogenic drivers of CNV in nAMD, and hyperoside (HYP)-a major flavonoid from Cuscuta chinensis, exhibits potent antioxidant and anti-inflammatory activities. These properties position HYP as a promising candidate for addressing the unmet treatment needs of nAMD and warrant further investigation into its mechanism of action in CNV modulation.

PURPOSE: This study aimed to explore the therapeutic potential of HYP-the main active component of the traditional Chinese herb Cuscuta chinensis Lam., and to elucidate its underlying molecular mechanisms in treating nAMD.

STUDY DESIGN: A combined in vivo and in vitro experimental strategy was adopted to systematically evaluate the therapeutic efficacy of HYP against nAMD and dissect the mechanistic basis of its action on CNV progression.

METHODS: This study adopted a multi-dimensional research approach: network pharmacology was first used to predict HYP's multi-target potential in regulating inflammation, oxidative stress, and vascular endothelial growth factor (VEGF) signaling; a murine model of laser-induced CNV was established to evaluate HYP's effects on CNV lesion area, retinal/choroidal damage, and inflammatory infiltration; reactive oxygen species (ROS) levels were detected, the expression of endogenous antioxidant enzymes (Cat, Nqo1, Sod2), Vegf, pro-inflammatory cytokines (Il-1β, Ccl2, Il-6, Tnf-α), and Wnt pathway-related genes (Myc, Plcb2, Rspo1, Wnt7a/7b, Ctnnb1) and protein (β-catenin); lipopolysaccharide (LPS)-stimulated ARPE-19 cells were used to corroborate HYP's antioxidant, anti-inflammatory effects, and Wnt pathway inhibition; molecular docking was employed to analyze the interaction between HYP and β-catenin; pharmacokinetic analysis was conducted to assess HYP's distribution in ocular tissues; and integrated transcriptomic analysis (RNA-seq) and Gene Expression Omnibus (GEO) database data analyses were performed to confirm the role of the Wnt pathway in human AMD and its correlation with intraocular inflammation.

RESULTS: Network pharmacology predicted that HYP has multi-target potential against inflammation, oxidative stress, and VEGF signaling; in the murine laser-induced CNV model, HYP treatment significantly reduced CNV lesion area, alleviated retinal/chorioretinal damage, and attenuated inflammatory infiltration; mechanistically, HYP effectively scavenged ROS, significantly upregulated the expression of endogenous antioxidant enzymes (Cat, Nqo1, Sod2), and downregulated the expression of Vegf, pro-inflammatory cytokines (Il-1β, Ccl2, Il-6, Tnf-α), key Wnt pathway genes (Myc, Plcb2, Rspo1, Wnt7a/7b, Ctnnb1), and the Wnt pathway's signature protein β-catenin; HYP's antioxidant, anti-inflammatory effects, and Wnt pathway inhibition were corroborated in LPS-stimulated ARPE-19 cells; molecular docking suggested a direct interaction between HYP and β-catenin; pharmacokinetic analysis showed favorable ocular distribution of HYP, supporting its biological relevance; and integrated transcriptomic and GEO data analyses confirmed the involvement of the Wnt pathway in human AMD and its correlation with intraocular inflammation.

CONCLUSION: Collectively, the findings demonstrate that HYP ameliorates CNV in nAMD through a concerted inhibition of oxidative stress, inflammation, and angiogenesis, primarily by suppressing Wnt/β-catenin signaling, which positions HYP as a promising multi-target candidate for the development of novel nAMD therapies.},
}

@article {pmid41719329,
year = {2026},
author = {Li, Y and Jing, M and Wang, W and Lin, W and Zhang, Y and Nie, T and Liu, P and Lu, WN and Chen, Y and Fielding Hejtmancik, J and Zheng, Q and Hou, L and Ma, X},
title = {DAPL1 restrains RPE PANoptosis in experimental AMD by inhibiting GRP75-mediated mitochondria-associated endoplasmic reticulum membranes.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {8},
pages = {e2511926123},
doi = {10.1073/pnas.2511926123},
pmid = {41719329},
issn = {1091-6490},
support = {2023YFC2506100//MOST | National Key Research and Development Program of China (NKPs)/ ; 82171065//MOST | National Natural Science Foundation of China (NSFC)/ ; 82571231//MOST | National Natural Science Foundation of China (NSFC)/ ; 82371081//MOST | National Natural Science Foundation of China (NSFC)/ ; },
mesh = {Animals ; Mice ; *Mitochondria/metabolism/pathology ; *Macular Degeneration/metabolism/pathology/genetics ; *Retinal Pigment Epithelium/metabolism/pathology ; *Endoplasmic Reticulum/metabolism ; Disease Models, Animal ; *HSP70 Heat-Shock Proteins/metabolism/genetics ; Mice, Knockout ; Humans ; *Membrane Proteins/metabolism/genetics ; Calcium/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/genetics ; *Adaptor Proteins, Signal Transducing/metabolism/genetics ; Mice, Inbred C57BL ; *Necroptosis ; Inflammasomes/metabolism ; },
abstract = {Retinal pigment epithelium (RPE) cell damage is a critical factor of age-related macular degeneration (AMD), the leading cause of blindness among the aged population. This study focuses on the AMD susceptible gene, Death associated protein like 1 (DAPL1), and provides insights with significant therapeutic implications. DAPL1-deficient mice exhibit dry AMD-like pathological features, a phenomenon whose mechanisms have remained largely unknown. Here, we reveal that DAPL1 deficiency promotes the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) to cause mitochondrial Ca[2+] overload and dysfunction, which triggers the activation of inflammasomes, leading RPE cells to RIPK1-mediated PANoptosis, an inflammatory programmed cell death, in an experimental dry AMD (dAMD) mouse model. Knockdown of Ripk1 in the Dapl1-/- mice RPE inhibits RPE cell PANoptosis and ameliorates the severity of dAMD pathological features. Conversely, overexpression of DAPL1 inhibits MAM formation and protects RPE cells from PANoptosis in the model. Mechanistically, DAPL1 suppresses MAM formation by downregulating GRP75 expression. This disrupts the formation of the VDAC-GRP75-IP3R axis, which comprises critical tethering proteins responsible for endoplasmic reticulum to mitochondria coupling and Ca[2+] trafficking. Knockdown of Grp75 inhibits the formation of MAM and prevents mitochondrial Ca[2+] overload, improving mitochondrial quality and inhibiting PANoptosis in RPE cells, thereby interrupting the progression of experimental dAMD in Dapl1-deficient mice. These results unveil the role of MAMs regulated by DAPL1 in RPE cell PANoptosis and AMD progression, highlighting targeting MAM formation as a potential therapeutic strategy for treating dAMD.},
}

Animals
Mice
*Mitochondria/metabolism/pathology
*Macular Degeneration/metabolism/pathology/genetics
*Retinal Pigment Epithelium/metabolism/pathology
*Endoplasmic Reticulum/metabolism
Disease Models, Animal
*HSP70 Heat-Shock Proteins/metabolism/genetics
Mice, Knockout
Humans
*Membrane Proteins/metabolism/genetics
Calcium/metabolism
Receptor-Interacting Protein Serine-Threonine Kinases/metabolism/genetics
*Adaptor Proteins, Signal Transducing/metabolism/genetics
Mice, Inbred C57BL
*Necroptosis
Inflammasomes/metabolism

@article {pmid41719023,
year = {2026},
author = {Anderer, S},
title = {Cataract Surgery Not Linked With Macular Degeneration Progression.},
journal = {JAMA},
volume = {},
number = {},
pages = {},
doi = {10.1001/jama.2025.26398},
pmid = {41719023},
issn = {1538-3598},
}

@article {pmid41717238,
year = {2026},
author = {Hwang, Y and Jamil, MU and Woo, KM and Kaiser, SM and Babiker, F and Rosenfeld, PJ and Waheed, NK and Fujimoto, JG},
title = {Large Hypertransmission Defects Exhibit Choriocapillaris Flow Speed Impairment in Nonexudative Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {3},
pages = {101060},
pmid = {41717238},
issn = {2666-9145},
abstract = {PURPOSE: To investigate choriocapillaris (CC) blood flow speed in regions associated with hypertransmission defects (hyperTDs) in nonexudative age-related macular degeneration (AMD) using variable interscan time analysis (VISTA) OCT angiography (OCTA).

DESIGN: Retrospective cross-sectional analysis of a prospectively collected cohort.

SUBJECTS: Thirty-one eyes from 29 subjects with nonexudative AMD.

METHODS: Patients with age-related macular degeneration were imaged using a 600 kHz A-scan rate prototype swept-source OCT with a 5 × 5 mm field of view and 5 B-scan repeats (1.25 ms interscan time). Hypertransmission defects were traced on choroidal en face projections and categorized by their greatest linear dimension (GLD): large (≥250 μm), medium (63-250 μm), and small (<63 μm). Choriocapillaris blood flow speed was quantified using VISTA, which measures OCTA signal saturation dynamics across multiple interscan times. Variable interscan time analysis flow speed (VFS) was evaluated at the macula and within hyperTDs. Choriocapillaris flow speed impairment (ΔVFS) for each hyperTD was calculated as the difference between its VFS and the macular average. To assess spatial extent, ΔVFS was assessed beyond lesion boundaries. Traditional metrics of OCTA signal and flow deficits (FDs) were also evaluated.

MAIN OUTCOME MEASURES: Choriocapillaris blood flow speed impairment (ΔVFS) within and around hyperTDs.

RESULTS: The macular average CC VFS was 1.47 ± 0.34 ms[-1], with no significant difference between eyes with (n = 14) and without (n = 17) hyperTDs. A total of 88 hyperTDs were analyzed: 19 large, 28 medium, and 41 small. Large hyperTDs showed significant CC flow impairment (ΔVFS = -0.37 ± 0.18 ms[-1], Padjusted < 0.0001), with impairment extending 100 μm beyond lesion boundaries (Padjusted = 0.0061). Medium-sized hyperTDs demonstrated moderate impairment (ΔVFS = -0.30 ± 0.47 ms[-1], Padjusted = 0.031), while small hyperTDs did not. In linear mixed-effects modeling, large and medium hyperTDs were associated with significant reductions in flow speed (-0.40 ms[-1], P = 0.014; -0.31 ms[-1], P = 0.030, respectively), corresponding to approximately 25% decreases from macular average. OCT angiography signal and FD metrics also detected size-dependent flow impairment.

CONCLUSIONS: Large hyperTDs in nonexudative AMD exhibit reduced CC flow speed extending beyond the lesion boundary. Longitudinal studies will investigate whether CC flow predicts onset and progression of hyperTDs.

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

@article {pmid41353311,
year = {2025},
author = {Willmington, C and Kirby, A and Murphy, A},
title = {The economic impact of retinal diseases for which gene therapy is emerging: a systematic literature review.},
journal = {Health economics review},
volume = {16},
number = {1},
pages = {21},
pmid = {41353311},
issn = {2191-1991},
support = {101073316//European Union's Horizon Europe/ ; },
abstract = {BACKGROUND: Retinal disease is one of the leading causes of blindness and vision impairment worldwide, including Europe. With the advent of gene therapy, the treatment landscape for retinal disease is changing and clinical trials are underway investigating the therapeutic potential of gene therapy in both acquired and inherited retinal diseases. Given the high price of innovative medicines, it is essential to consider the current costs associated with retinal diseases to inform economic evaluations early in the life cycle of these forthcoming treatments. These could inform future reimbursement decisions, health budgets and service delivery plans.

AIM: This systematic literature review sought to examine the economic burden of retinal diseases, for which gene therapy is emerging for patients in Europe.

METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guideline, a systematic search was performed using the Medline, CINAHL, EconLit and Embase databases. The searches were restricted to English language articles published after 1st January 2000. Following article selection, data were extracted in a tabular form and a narrative synthesis was performed.

RESULTS: A total of 28 research studies were identified and included in the review that varied in terms of disease of interest, size, country setting, methodology, as well as how costs were reported and valued. While many retinal diseases were considered, almost half of the articles related to the costs of neovascular age-related macular degeneration (nAMD). Significant cost variations were observed across the studies as costs ranged from 45 USD to almost 30,000 USD per patient per annum, across all conditions combined.

CONCLUSION: This systematic literature review evidences the heterogeneity among studies analysing the economics of retinal diseases underlying vision impairment. The paucity in the literature, signals the need for further research investigating the costs associated with retinal diseases, for which innovative therapies are expected to enter the market and will be subject to evaluation by decision-makers, whose decisions will have a significant impact on the delivery of these technologies to patients.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13561-025-00707-7.},
}

@article {pmid41717163,
year = {2026},
author = {Sourla, E and Zaheer, N and Chavan, R},
title = {Switching From Intravitreal Ranibizumab (Lucentis) to Biosimilar Ranibizumab (Ongavia) Injections: Insights From a Tertiary Care Eye Centre.},
journal = {Cureus},
volume = {18},
number = {1},
pages = {e101850},
pmid = {41717163},
issn = {2168-8184},
abstract = {BACKGROUND: Ranibizumab has been widely used to treat retinal conditions such as wet age-related macular degeneration, diabetic macular oedema, and macular oedema secondary to retinal vein occlusions. In 2022, the Medicines and Healthcare products Regulatory Agency (MHRA) approved Ongavia, the first biosimilar of ranibizumab. Ongavia offers comparable efficacy and safety, with a similar side effect profile to the original medication, while being more cost-effective.

METHOD: The study was conducted in the medical retina department of a tertiary care eye hospital. Data were collected from patients undergoing treatment with intravitreal ranibizumab (Lucentis) who were switched to the ranibizumab biosimilar, Ongavia, between November 2023 and February 2024. This study included two components. The first was a cross-sectional observational survey, in which patients being switched to Ongavia completed a satisfaction questionnaire regarding the information leaflet received and the discussions held about the switch. The second component was a retrospective review to assess the effectiveness and safety of ranibizumab biosimilar Ongavia in patients with wet AMD. After two Ongavia injections, the treatment interval for the next injection was reviewed and compared with the treatment interval with ranibizumab. Similarly, OCT scans before and after the switch were reviewed and compared. Any adverse effects documented in the clinical notes were recorded.

RESULTS: Out of 121 eyes, 92 eyes (76%) were switched to biosimilar ranibizumab (Ongavia) injections, while 18 eyes (15%) continued receiving ranibizumab injections. Patient satisfaction with the information process was 100%. Eighty-seven eyes of patients with wet AMD received more than two Ongavia injections as per the treat-and-extend protocol. Out of these 87 eyes, in 64 eyes (73.5%), injection intervals were either maintained or extended. The treatment interval was reduced in seven eyes (8%), and nine eyes (10.3%) were switched to a different anti-VEGF medication. No safety concerns were identified with biosimilar ranibizumab.

CONCLUSIONS: Patient satisfaction with the information process was high, likely due to active involvement in treatment decision-making. The results indicate that the clinical effectiveness of ranibizumab biosimilar Ongavia is comparable to ranibizumab and that it has a similar safety profile. Ongavia could serve as a cost-effective alternative, reducing healthcare system costs while maintaining high standards of patient care.},
}

@article {pmid41717027,
year = {2026},
author = {Cen, S and Li, J and Reilly, J and Chen, J and Jiang, HR and Shu, X},
title = {The therapeutic potential of gypenosides for age-related macular degeneration.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1773391},
pmid = {41717027},
issn = {2296-861X},
}

@article {pmid41716779,
year = {2026},
author = {Hahn, W and Erffmeier, K and Schulze, M and Zahnert, F and Knake, S and Tsalouchidou, PE},
title = {Intermittent ketogenic fasting with medium-chain triglycerides improves ataxia in COQ8A-related coenzyme Q10 deficiency: A case report.},
journal = {Molecular genetics and metabolism reports},
volume = {46},
number = {},
pages = {101296},
pmid = {41716779},
issn = {2214-4269},
abstract = {BACKGROUND: Mutations in COQ8A cause primary coenzyme Q10 deficiency, which can present clinically heterogeneously: Symptoms range from cerebellar ataxia, epilepsy, encephalomyopathy, macular degeneration to nephropathy. High-dose coenzyme Q10 supplementation is widely used, yet there is little evidence on complementary strategies, particularly for non-epileptic features such as cerebellar ataxia.

CASE PRESENTATION: We report a 46-year-old female with genetically confirmed COQ8A-related coenzyme Q10 (CoQ10) deficiency, presenting with ataxia and epilepsy characterized by myoclonic and bilateral tonic-clonic seizures, who participated in a clinical protocol of ketogenic intermittent fasting, a method of intermittent fasting combined with medium-chain triglycerides (MCT) primarily designed for seizure management. The patient followed a 16:8 intermittent fasting regime combined with MCT intake for three months, followed by three months of all-alone intermittent fasting. Routine blood markers and brain MRI, including diffusion imaging were obtained before and after ketogenic fasting.

RESULTS: During the study protocol, while no seizure reduction in myoclonic seizures could be observed, ataxia - quantified by the Scale for the Assessment and Rating of Ataxia (SARA) - improved significantly from 8.5 to 6.0 during the interventions. MRI showed a trend suggesting improved cerebellar microstructural integrity.

CONCLUSIONS: This case highlights the potential of ketogenic intermittent fasting as an adjunct therapy for mitochondrial ataxia. Ketogenic intermittent fasting was associated with clinically meaningful improvement of ataxia in a patient with COQ8A-related CoQ10 deficiency, suggesting that ketogenic dietary strategies may represent a promising adjunct therapeutic approach for mitochondrial ataxia. Future research should assess this intervention in larger patient cohorts to confirm its potential benefits.},
}

@article {pmid41716622,
year = {2026},
author = {Rohowetz, LJ and Flynn, HW and Townsend, JH},
title = {A second occurrence of intravitreal injection-associated endophthalmitis 2 years apart.},
journal = {American journal of ophthalmology case reports},
volume = {42},
number = {},
pages = {102525},
pmid = {41716622},
issn = {2451-9936},
abstract = {PURPOSE: This case report describes a patient who developed a second episode of endophthalmitis in the same eye following intravitreal injections administered 2 years apart.

OBSERVATIONS: An 83-year-old pseudophakic male with a history of neovascular age-related macular degeneration and diabetes mellitus complained of decreased visual acuity and pain in the left eye 1 day after receiving intravitreal aflibercept 2 mg. Best-corrected visual acuity (BCVA) was light perception. The clinical examination revealed signs of endophthalmitis including fibrin and hypopyon while B-scan ultrasonography demonstrated vitreous opacities and membranes. The patient underwent vitreous tap and injection with intravitreal vancomycin, ceftazidime, and dexamethasone. Pars plana vitrectomy with posterior hyaloid detachment was performed the following day due to a relative lack of clinical improvement. Vitreous cultures ultimately demonstrated no growth and BCVA improved to baseline. Anti-VEGF therapy was resumed 3 months after the initial diagnosis of endophthalmitis. Two years later the patient presented with evidence of a second episode of endophthalmitis 4 days after receiving aflibercept 8 mg. Vitreous tap and injection was again performed and cultures revealed growth of Staphyloccoccus epidermidis. The patient demonstrated marked improvement with no evidence of residual inflammation at 2 weeks. Best-corrected visual acuity was 20/50 at 7-month follow-up examination.

CONCLUSION AND IMPORTANCE: Endophthalmitis is a rare complication of intravitreal injection. The current report describes a patient who developed a second occurrence of endophthalmitis associated with an intravitreal injection 2 years later.},
}

@article {pmid41716475,
year = {2026},
author = {Al-Latayfeh, M and Aleshawi, A and El-Mulki, OS and Baker, M and Qaddoumi, Z and Attar, D and Alma'aitah, L and Jarrah, EZ and Abu Khalil, Z and Awad, W and Dayeh, MR and Al Beiruti, S and Al-Dwairi, R},
title = {Accuracy and Reproducibility of Different Artificial Intelligence Chatbots' Responses to Patient-Based Vitreoretinal Questions: A Comparative Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {580133},
pmid = {41716475},
issn = {1177-5467},
abstract = {BACKGROUND: Generative artificial intelligence (AI) chatbots are increasingly used by patients and their reliability in complex ophthalmic conditions remains uncertain. This study aimed to compare the accuracy, comprehensiveness, and reproducibility of five AI chatbots-ChatGPT-5.o, DeepSeek R1, Meta AI, Grok 3.0, and Google Gemini 2.5 Pro-in responding to patient-centered vitreoretinal questions.

METHODS: A total of 135 questions covering diabetic retinopathy, floaters/flashes, age-related macular degeneration, retinal tear/detachment, and vitrectomy were sourced from the American Academy of Ophthalmology "Ask an Ophthalmologist" database. Each question was submitted twice to each chatbot under standardized instructions. Two board-certified vitreoretinal ophthalmologists independently graded responses for accuracy and reproducibility. Accuracy was calculated as the proportion of responses graded "Correct and Comprehensive" or "Accurate but incomplete"; reproducibility was defined as agreement between the two responses.

RESULTS: ChatGPT-5.o achieved the highest overall accuracy (94%, n=127/135, 95% CI: 89.9%-98.1%) with a reproducibility rate of 96.3% (n=130/135, 95% CI: 93.1%-99.5%). DeepSeek R1 demonstrated the greatest reproducibility (98.5%, n=133/135, 95% CI: 96.5%-100.0%) and high accuracy (92.6%, n=125/135, 95% CI: 88.1%-97.1%). Meta AI showed 91% (95% CI: 86.1%-95.9%) accuracy and 94% (95% CI: 89.9%-98.1%) reproducibility, whereas Grok 3.0 yielded the lowest accuracy (49.6%, n=67/135, 95% CI: 41.2%-58.0%) despite moderate reproducibility (88.1%, n=119/135, 95% CI: 82.7%-93.5%). Google Gemini 2.5 Pro recorded 72.6% (95% CI: 65.1%-80.1%) accuracy and the lowest reproducibility (77%, 95% CI: 69.9%-84.1%). By category, "Vitrectomy" scored the highest across all chatbots (94%, 95% CI: 87.2%-100.0%), followed by "Macular degeneration" (90%, 95% CI: 85.0%-95.0%). However, the category "Diabetic retinopathy" scored the lowest accuracy rate (64.7%, 95% CI: 52.1%-77.3%).

CONCLUSION: ChatGPT-5.o and DeepSeek R1 approached high accuracy and reproducibility comparable to clinical standards, indicating potential as patient-education tools in vitreoretinal care. However, variability across models and disease categories highlights the need for cautious clinical adoption and continued optimization to ensure safe, reliable information delivery.},
}

@article {pmid41714517,
year = {2026},
author = {Shen, Y and Chen, Q and He, X and Agrawal, R and Grzybowski, A and Jin, K and Ye, X},
title = {Automated Report Generation in Ophthalmology: Integrating Artificial Intelligence, Multimodal Imaging, and Clinical Data.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41714517},
issn = {2193-8245},
support = {QZYY-2025-225//Project on Scientific and Technological Research of Traditional Chinese Medicine and Ethnic Medicine in Guizhou Province/ ; gzwkj2025-099//Science and Technology Fund Project of Guizhou Provincial Health Commission/ ; },
abstract = {Artificial intelligence (AI) has emerged as a transformative force in ophthalmology, enabling automated, accurate, and efficient clinical reporting. This review summarizes recent advances in AI-driven report generation, emphasizing the integration of multimodal imaging and clinical data. Deep learning and natural language processing (NLP) models can synthesize information from diverse sources-including fundus photography, optical coherence tomography, fluorescein angiography, and patient records-to generate structured, interpretable, and personalized diagnostic reports. Such systems enhance diagnostic precision, streamline workflow, and reduce interobserver variability. We outline the technological foundations underlying these systems, including convolutional and transformer-based architectures, self-supervised and multimodal learning, and large language models. Representative applications in diabetic retinopathy, glaucoma, cataract, and age-related macular degeneration are discussed, highlighting their clinical value and emerging real-world deployment. Persistent challenges-including data heterogeneity, model interpretability, ethical governance, and clinical integration-are critically reviewed. Finally, we explore future directions such as real-time AI-assisted reporting, predictive and personalized analytics, and global scalability across healthcare ecosystems. Multimodal, explainable, and clinically integrated AI systems hold promise to redefine ophthalmic diagnostics and improve both clinician efficiency and patient outcomes.},
}

@article {pmid41714388,
year = {2026},
author = {Sadeghi, E and DeCicco, J and Gandhi, P and Hasan, N and DiCenzo, B and Jiang, JY and Rahmanipour, E and Sahel, JA and Eller, AW and Chhablani, J},
title = {Differentiation of macular atrophy secondary to neovascular age-related macular degeneration vs. de novo geographic atrophy: a multimodal analysis.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41714388},
issn = {1476-5454},
abstract = {PURPOSE: To compare macular atrophy following neovascular age-related macular degeneration (nAMD) vs. geographic atrophy (GA) following dry AMD.

METHODS: We analysed 60 eyes from 44 patients: 30 eyes with de novo GA and 30 with macular atrophy secondary to nAMD. All patients had monthly follow-ups before GA onset and continued for at least two years after. GA was defined as complete retinal pigment epithelium atrophy ≥250 μm using OCT scans. OCT biomarkers at GA onset, including central macular thickness (CMT), subfoveal choroidal thickness (SFCT), epiretinal membrane (ERM), double-layer sign (DLS), subretinal hyperreflective material (SRHM), hyperreflective foci (HRF), outer retinal tubulation (ORT), and intraretinal fluid (IRF), were assessed. Chi-square test, Spearman correlation, and linear mixed models were used.

RESULTS: The mean age was 80.06 ± 8.60 years, with 50.0% male. Eyes with nAMD progressed to macular atrophy after 31.38 ± 30.72 months and 8.86 ± 10.84 anti-vascular endothelial growth factor (VEGF) injections. Compared to de novo GA, eyes with macular atrophy following nAMD had larger baseline atrophic area (3.791 ± 2.661 mm² vs. 1.115 ± 0.951 mm²; P < 0.001) and greater atrophy growth (2.646 ± 2.014 mm² vs. 0.652 ± 0.722 mm²; P < 0.001), with more frequent ERM, DLS, HRF, SRHM, ORT, and IRF. Atrophy growth correlated with baseline SFCT (r = -0.545, P = 0.002) and GA area (r = 0.501, P = 0.005) but not with the number of anti-VEGF injections (p > 0.05).

CONCLUSION: Eyes with macular atrophy secondary to nAMD exhibit larger initial atrophic areas and faster progression compared to de novo GA. OCT biomarkers may detect previous exudation, helping identify cases where recently FDA-approved GA therapies may be relatively contraindicated due to prior disease.},
}

@article {pmid41713794,
year = {2026},
author = {Liao, X and Lou, J and Liu, C and Wang, Y and Zhu, G and Ke, Y and Bai, M and Yang, P and Yang, W and Chi, W},
title = {Advancements in OCT and OCTA Imaging for AMD: An In-depth Analysis of Research Hotspots, Emerging Trends, and Technological Innovations.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105402},
doi = {10.1016/j.pdpdt.2026.105402},
pmid = {41713794},
issn = {1873-1597},
abstract = {PURPOSE: To map research hotspots and emerging trends of Optical Coherence Tomography (OCT) and Optical Coherence Tomography Angiography (OCTA) in Age-related Macular Degeneration (AMD) from 2015-2024 using bibliometric analysis.

METHODS: We searched the Web of Science Core Collection (2015-2024) on January 2025, identified 2,471 English-language articles on OCT/OCTA in AMD, and extracted data on countries, institutions, journals, keywords, and citations. CiteSpace 6.4 and Excel were used for co-occurrence/co-citation analyses and visualization; H-indexes were compiled for countries and institutions.

RESULTS: Seventy-eight countries/regions contributed to the field; the United States led in publications and H-index, followed by China. Among 200 institutions, the University of California System produced the most studies and showed the highest influence. Publication output increased steadily (R[2]≈0.69). Core topics clustered around geographic atrophy (GA), choroidal neovascularization (CNV), ranibizumab, OCT, and AMD. Recent keyword bursts highlighted macular neovascularization (MNV), hyperreflective foci (HRF), deep learning, impact, and growth. High-impact literature underscored OCT/OCTA's noninvasive vascular imaging utility, anti-VEGF treatment outcomes, GA progression metrics, and rapid advances in AI-driven detection/segmentation and prognostication. Meta-analyses reported high diagnostic accuracy of OCTA for CNV, while technical challenges (e.g., signal-to-noise) persist. Emerging themes include multimodal integration, biomarkers such as hyperreflective foci for prognosis, and time-series/AI models for predicting GA/CNV trajectories and personalizing treatment intervals.

CONCLUSION: OCT and OCTA research in AMD has expanded substantially, with the U.S. and leading academic centers driving influence. Integrating AI with OCT/OCTA enables earlier detection, refined phenotyping, and data-informed, personalized management. Advancing precision and standardization will further improve diagnostic accuracy and therapeutic decision-making in AMD.},
}

@article {pmid41713160,
year = {2026},
author = {Ashrafi, S and Sajedi, H},
title = {Task-specific neural networks for medical imaging using pretrained fragments.},
journal = {Computers in biology and medicine},
volume = {204},
number = {},
pages = {111545},
doi = {10.1016/j.compbiomed.2026.111545},
pmid = {41713160},
issn = {1879-0534},
abstract = {The StitchNet framework introduced a paradigm shift in Neural Architecture Search (NAS) by proposing the construction of neural networks from pre-trained fragments. This approach reduces computational costs and enables task-specific model creation without retraining entire networks. Building on this foundation, our study evaluates the practical application of StitchNet in constructing neural networks tailored to medical image classification tasks. Specifically, we assess its performance on a dataset of retinal images classified into three categories: healthy, dry, and wet AMD (Age-Related Macular Degeneration), namely drusen and choroidal neovascularization (CNV). By employing fragments from five pre-trained networks and integrating techniques such as recurrent neural networks (RNNs) and autoencoders, we aim to validate and enhance StitchNet's capabilities. Our findings demonstrate that while StitchNet achieves competitive accuracy with reduced computational overhead, incorporating domain-specific optimizations further improves its adaptability and efficiency. So, the developed network outperforms a scientist-designed network by 6%. In the next phase, we will explore ways to improve the algorithm's efficiency and minimize the data required for processing. Fully reproducible code here: https://github.com/ShafighAshrafi/stitchnet.},
}

@article {pmid41712907,
year = {2026},
author = {Sather, RN and Chiang, T and Moon, JY and Dev, S and Belin, PJ},
title = {Real-World Durability of Aflibercept 8 mg and Faricimab in Initiators Versus Switchers: A Multicenter Retrospective Analysis.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004813},
pmid = {41712907},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate real-world differences in treatment durability, functional, and anatomical outcomes in patients who initiated or switched to aflibercept 8 mg or faricimab.

METHODS: Patients were categorized into four cohorts: (1) initiators of aflibercept 8 mg, (2) initiators of faricimab, (3) switchers to aflibercept 8 mg, and (4) switchers to faricimab. Switchers were further stratified as early (≤5 prior injections) or late (>5 injections). Treatment durability was assessed using the mean treatment interval, defined as the average of the three most recent injection intervals before or after the switch. Multivariate linear regression models were used to assess the independent effect of treatment strategy on durability, best-corrected visual acuity (BCVA), and central subfield thickness (CST).

RESULTS: A total of 10,247 patients (12,501 eyes) with either nAMD, DME, or RVO initiated aflibercept 8 mg or faricimab. Initiators achieved greater mean treatment intervals (10 weeks) than switchers (9 weeks post-switch; p < 0.01). Early switchers showed greater durability and CST reduction (-66 µm) than late switchers (-19 µm; p < 0.01). Faricimab initiators had greater durability (p < 0.01) and CST reductions (p = 0.01) compared to other cohorts. Medicare coverage was associated with longer durability than Medicare Advantage recipients (p < 0.01).

CONCLUSION: In this real-world cohort, initiation of faricimab or aflibercept 8 mg was associated with greater treatment intervals and improved anatomical outcomes compared to eyes that were switched from older anti-VEGF agents. These findings support early initiation of these anti-VEGF therapies and that step-therapy delays may compromise clinical outcomes.},
}

@article {pmid41712218,
year = {2026},
author = {Pitcher, JD and Koh, AHC and Tan, CS and Vakharia, P and Dagincourt, N and Patel, S and Yang, M and Margaron, P and Gallego-Pinazo, R},
title = {Rapid Fluid Resolution and Durability With Faricimab in Neovascular Age-Related Macular Degeneration.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.6365},
pmid = {41712218},
issn = {2168-6173},
abstract = {IMPORTANCE: In the TENAYA and LUCERNE randomized clinical trials (RCTs), approximately 80% of study participants with treatment-naive neovascular age-related macular degeneration (nAMD) achieved at least every-12-week faricimab dosing at week 112. Subsequent post hoc analyses showed more rapid drying with faricimab compared with aflibercept, 2 mg, during the initial head-to-head dosing phase (weeks 0-12).

OBJECTIVE: To investigate whether rapid drying with faricimab, specifically intraretinal fluid (IRF) and subretinal fluid (SRF) resolution through week 12, is associated with later treatment durability.

This is a post hoc analysis of faricimab-treated study participants from the TENAYA and LUCERNE RCTs, which were randomized, double-masked, multicenter, noninferiority studies of the efficacy and safety of faricimab, 6 mg, up to every 16 weeks vs aflibercept, 2 mg, every 8 weeks. Study participants in this post hoc analysis were those who had treatment-naive nAMD and were in the faricimab arm of TENAYA and LUCERNE. Data analysis was performed from July 2024 to December 2025.

INTERVENTION: Faricimab, 6 mg, up to every 16 weeks after 4 loading doses (received once every 4 weeks). Following disease activity assessments at week 20 or 24, participants received fixed dosing up to every 16 weeks until week 60 and then a treat-and-extend-based dosing regimen.

MAIN OUTCOMES AND MEASURES: Multinomial logistic regression modeling was used to test the association between resolution of IRF and SRF through week 12 and the faricimab treatment interval at week 20 or 24 (the first opportunity to extend treatment intervals) and at week 112 (study completion).

RESULTS: This analysis included 552 participants with their dosing interval at week 20 or 24 available (265 participants with IRF and SRF resolution and 287 without resolution); among them, 478 patients had their dosing interval at 112 weeks available (223 participants with IRF and SRF resolution and 255 without resolution). Study participants with IRF and SRF resolution through week 12, compared with those without resolution through week 12, were more likely to receive every-16-week dosing than every-8-week dosing (odds ratio [OR], 1.99; 95% CI, 1.23-3.21; P = .005) and to receive every-12-week dosing than every-8-week dosing (OR, 1.77; 95% CI, 1.09-2.87; P = .02) at week 20 or 24, and they were more likely to receive every-16-week dosing than every-8-week dosing at week 112 (OR, 1.76; 95% CI, 1.10-2.83; P = .02).

CONCLUSIONS AND RELEVANCE: These findings suggest that rapid fluid resolution through week 12 with faricimab may be a predictor of extended durability (dosing intervals of every 12 weeks or longer) in participants with nAMD.

TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT03823287 and NCT03823300.},
}

@article {pmid41712059,
year = {2026},
author = {Barbosa, M and Bartolomeo, N and Schuetz, YP and Nascimbeni, AC and Castro, DG and Barry, MP and Ambresin, A},
title = {Loading dose and 12-month outcomes in treatment-naïve patients with neovascular age-related macular degeneration treated with faricimab, with AI-based analysis of fluid dynamics.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {124},
pmid = {41712059},
issn = {1573-2630},
mesh = {Humans ; Male ; Female ; Intravitreal Injections ; *Visual Acuity ; Aged ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; Angiogenesis Inhibitors/administration & dosage ; Treatment Outcome ; Aged, 80 and over ; Follow-Up Studies ; Fluorescein Angiography/methods ; *Artificial Intelligence ; Hydrodynamics ; Dose-Response Relationship, Drug ; Time Factors ; Fundus Oculi ; Middle Aged ; Subretinal Fluid ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To evaluate the effects of loading dose and 12 months of faricimab treatment on visual function, retinal anatomy, and fluid dynamics in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

METHODS: Patients received intravitreal faricimab 6 mg monthly (to Month 4) followed by personalized treat-and-extend regimens allowing 4-week interval adjustments. Best-corrected visual acuity (BCVA), retinal anatomy, and fluid dynamics (evaluated using an artificial intelligence-based automated fluid quantification system) were assessed monthly to Month 4, then at Months 6, 9, and 12.

RESULTS: Fifty-one patients (57 study eyes; mean [SD] BCVA: 66.5 [13.4] letters; mean [SD] central retinal thickness [CRT]: 340.7 [84.7] μm at baseline) were enrolled. Significant improvements in mean BCVA (+ 3.3 letters; P < 0.001) and CRT (- 70.5 μm; P < 0.001) were observed by Month 4. Maximal pigment epithelium detachment (PED) height reduced significantly from baseline to Month 4. Improvements were maintained to Month 12. Intra- and subretinal fluid and PED volumes were significantly reduced versus baseline at all time points. At Month 12, 73.3% of patients were on treatment intervals of 12 weeks or longer. Three adverse events were observed, including one mild intraocular inflammation.

CONCLUSION: Treatment with faricimab resulted in rapid and sustained functional and anatomical improvements in treatment-naïve nAMD.},
}

Humans
Male
Female
Intravitreal Injections
*Visual Acuity
Aged
*Wet Macular Degeneration/drug therapy/diagnosis/physiopathology
Tomography, Optical Coherence/methods
Angiogenesis Inhibitors/administration & dosage
Treatment Outcome
Aged, 80 and over
Follow-Up Studies
Fluorescein Angiography/methods
*Artificial Intelligence
Hydrodynamics
Dose-Response Relationship, Drug
Time Factors
Fundus Oculi
Middle Aged
Subretinal Fluid
Antibodies, Bispecific

@article {pmid41711523,
year = {2026},
author = {He, R and Ding, W and Cao, J and Guo, C and Li, X and Xiao, G},
title = {Ergothioneine: Evaluation of a Novel Antioxidant for Targeting Ocular Oxidative Stress.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/02713683.2026.2618755},
pmid = {41711523},
issn = {1460-2202},
abstract = {PURPOSE: To evaluate ergothioneine (EGT), a naturally occurring amino acid and endogenous antioxidant, as a novel therapeutic agent for oxidative stress-related ocular diseases. This evaluation specifically aimed to address the challenge of targeted ocular delivery by assessing EGT's antioxidant potency, stability, ocular tolerance, and crucially, its ability to reach the posterior segment (fundus) via topical administration.

METHODS: This study evaluated EGT as a novel ocular antioxidant by examining its radical scavenging capacity (DPPH assay compared to glutathione, astaxanthin, and coenzyme Q10), stability (at 40 °C/75% relative humidity for six months using HPLC), ocular tolerance (using a New Zealand rabbit model), and fundus delivery efficiency (topical D9-EGT eye drops quantified by LC-MS/MS).

RESULTS: EGT demonstrated significantly superior radical scavenging activity, exhibiting 6.4-fold and 46-fold higher rates than glutathione and coenzyme Q10, respectively, at 50 ppm. It also showed excellent stability, retaining over 97% of its initial concentration after six months, and caused no ocular irritation at any tested concentration (score 0). Importantly, topical administration of EGT resulted in effective fundus delivery, with peak concentrations reached at 0.5 h post-application (1181 ± 56 ng/g), confirming successful penetration through corneal and scleral barriers. These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops.

CONCLUSION: These findings establish EGT as a potent, multi-mechanistic antioxidant characterized by high stability, ocular safety, and exceptional posterior segment penetrance via noninvasive eye drops. By overcoming key delivery limitations, EGT presents a promising therapeutic strategy for oxidative stress-related ocular diseases such as age-related macular degeneration and diabetic retinopathy. Further studies are warranted to evaluate its long-term efficacy and clinical translation potential.},
}

@article {pmid41710168,
year = {2026},
author = {Estreicher, A and Biedka, K and Błaszczyk, K and Wesołowski, M and Bulski, J and Sobaś, AE and Ziobro, O and Maj, FJ and Sornat, KB and Klasa, AM and Żełabowski, K and Karwacki, J and Sebzda, T},
title = {The Amsler Grid in Everyday Practice: A Review of Its Role and Limitations in Primary Care.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {542357},
pmid = {41710168},
issn = {1177-5467},
abstract = {This narrative review provides a comprehensive overview of current evidence on the use of the Amsler grid as a simple and cost-effective tool for detecting central visual field defects, particularly in macular disorders such as age-related macular degeneration (AMD). Despite the availability of advanced imaging techniques like optical coherence tomography (OCT), the grid remains valuable in primary care and home monitoring due to its accessibility and ease of use. This review includes studies evaluating its diagnostic performance, clinical applications, and recent digital adaptations, with a focus on early detection and patient self-monitoring. It facilitates early detection of visual disturbances, enabling timely diagnosis and intervention. The test is applicable in various retinal conditions, including AMD, diabetic macular edema, central serous chorioretinopathy, and epiretinal membrane. Although its diagnostic accuracy varies depending on the condition and stage, clinical studies support its reliability as an adjunctive tool in everyday practice. Recent developments include mobile and web-based platforms, as well as integration with artificial intelligence, which may enhance diagnostic accuracy, enable longitudinal monitoring, and improve patient adherence. Early detection is crucial for preserving vision and reducing the global burden of visual impairment.},
}

@article {pmid41709226,
year = {2026},
author = {Villarruel Hinnerskov, JM and Nielsen, MK and Thomsen, AK and Steffensen, MA and Honoré, B and Vorum, H and Nissen, MH and Sørensen, TL},
title = {Complement regulatory proteins are associated with progression rate of geographic atrophy secondary to age-related macular degeneration.},
journal = {Immunity & ageing : I & A},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12979-026-00562-y},
pmid = {41709226},
issn = {1742-4933},
}

@article {pmid41709128,
year = {2026},
author = {Öncül, H and Dertsiz Kozan, B and Dağ, U and Çağlayan, M and Alakuş, MF and Temel, C and Utlu, ES},
title = {Evaluation of primary care physicians' knowledge, attitudes, and awareness levels regarding age-related macular degeneration.},
journal = {BMC primary care},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12875-026-03228-2},
pmid = {41709128},
issn = {2731-4553},
}

@article {pmid41708012,
year = {2026},
author = {Stuard Sambhariya, W and Bowes Rickman, C and D'Amore, PA and Corradetti, G and Hageman, GS and Howell, GR and Marola, OJ and Phatnani, H and Philp, NJ and Sinha, D and Toomey, CB and Stone, F and Eberhart, C and Handa, JT},
title = {Age-related macular degeneration and cerebral amyloid angiopathy have similar pathologies from cholesterol-APOE-amyloid-β-complement mediated inflammation.},
journal = {Progress in retinal and eye research},
volume = {111},
number = {},
pages = {101449},
doi = {10.1016/j.preteyeres.2026.101449},
pmid = {41708012},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) and Alzheimer's disease (AD) are neurodegenerative conditions that afflict millions of elderly people around the world. AMD is a progressive retinal disorder that leads to central vision loss whereas AD primarily causes cognitive decline and behavioral changes. While each disease has distinct clinical manifestations, the accumulation of extracellular amyloid-β is a common histopathologic finding. Similarly, cerebral amyloid angiopathy (CAA), a vascular condition that can exist independent or with AD, is characterized by the accumulation of amyloid-β in cerebral blood vessels. While significant investigation of the pathophysiologic links between AMD and AD has been conducted, the underlying similarities and differences in the pathobiology of AMD and CAA has not been considered. In this review, we discuss the common pathological features of these two conditions. We then discuss the similar pathobiology that involves cholesterol metabolism, apolipoprotein E, amyloid-β, and complement mediated inflammation. At the same time, we discuss key differences in their pathobiology. This discussion sheds new perspective and insights of their pathobiology.},
}

@article {pmid41707600,
year = {2026},
author = {Posnic, A and Vaast, M and Poinas, A and Le Pabic, E and Bellamy, JP and Delhay, C and Faure, S and Le Rouic, JF and Henry, A and Lebreton, O and Masse, H and Guillaumie, T and Fournier, I and Mainguy, A and Le Lez, ML and Khanna, RK and George, A and Pipelart, V and Bernard, Y and Grimbert, P and Mazhar, D and Benzerroug, M and Briend, B and Clement, M and Jammes-Veaux, HP and Posnic, MP and Bonissent, A and Guyot, C and Rousseau, N and Trinh Van Dam, B and Bellot, L and Ferron, R and Le Meur, G and Mouriaux, F and Weber, M and Maucourant, Y and Ducloyer, JB},
title = {Extension of the intravitreal injection interval after switching to faricimab in patients with exudative AMD: The multicenter FAR WEST study.},
journal = {Journal francais d'ophtalmologie},
volume = {49},
number = {3},
pages = {104795},
doi = {10.1016/j.jfo.2026.104795},
pmid = {41707600},
issn = {1773-0597},
abstract = {PURPOSE: To assess whether switching to faricimab allowed extending injection intervals without exudation in patients with neovascular age-related macular degeneration (nAMD) and to identify predictive factors for interval extension.

METHODS: FAR WEST was a multicenter, observational retrospective cohort study, including patients with nAMD treated with intravitreal anti-VEGF injections (IVI) for at least one year prior to switching to faricimab. Data were collected from the medical records at the time of the decision to switch to faricimab (M0) and at the M6 follow-up visit. The switch strategy (whether an induction phase was performed or not) was left to the practitioner's discretion.

RESULTS: A total of 814 eyes of 705 patients were included in 23 centers. The recurrence-free IVI interval increased significantly from 5.6 weeks at M0 to 7.2 weeks at M6 (+1.6 weeks, P<0.0001). The proportion of exudative patients decreased by 37% (P<0.0001). Among 228 refractory cases at M0, 88 (39%) achieved a dry macula at M6. A greater interval extension was found in patients who underwent immediate extension. No significant differences were observed in terms of age, time since first injection, type of neovascularisation, or pre-switch IVI interval. The intraocular inflammation rate was 0.6% (n=5).

CONCLUSION: Switching to faricimab allowed for significantly extending the recurrence-free IVI interval and decreasing the proportion of exudative patients in this cohort. Significant extension was found in a wide range of patients, including those without a loading phase. Further controlled prospective studies are needed to assess the value of a loading phase when switching to faricimab. Safety outcomes were consistent with prior studies.},
}

@article {pmid41707077,
year = {2026},
author = {Pandya, BU and Mihalache, A and Huang, RS and Jhaveri, A and Cao, X and Ballios, B and Felfeli, T},
title = {Effectiveness and Safety of Biosimilar Anti-Vascular Endothelial Growth Factor for Retinal Diseases: A Systematic Review and Meta-Analysis.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004807},
pmid = {41707077},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the comparative effectiveness and safety of biosimilar anti-vascular endothelial growth factor (VEGF) versus reference anti-VEGF intravitreal injections for the treatment of retinal diseases.

METHODS: A systematic review and meta-analysis was performed on studies identified through searches of OVID MEDLINE, Embase, and the Cochrane Library between January 2015 and September 2024. Studies evaluating effectiveness and/or safety outcomes of biosimilar anti-VEGF were included. Meta-analysis was performed with a random effects model. Risk of bias (ROB) assessment was performed with the Joanna Briggs Institute (JBI) tools, and certainty of evidence was evaluated with the GRADE criteria.

RESULTS: A total of 25 studies were included in the meta-analysis. Diagnoses studied were neovascular age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and polypoidal choroidal vasculopathy. There were no significant differences in final visual acuity (VA), change in VA, final retinal thickness (RT), change in RT, and incidence of adverse events over a follow-up duration of 12-63.6 weeks. Subgroup analyses of randomized controlled trials, observational studies, AMD, DME, and agent-specific analysis (aflibercept and ranibizumab) were not significant. Findings are supported by evidence of moderate to high certainty as per the GRADE tool. There was a low to moderate ROB in the included study as per the JBI tool.

CONCLUSION: Biosimilar anti-VEGF is comparable to reference anti-VEGF with respect to safety profile and visual outcomes. Future research should prioritize including diverse patient populations and adopting standardized, extended follow-up periods to enhance the assessment of long-term safety and effectiveness of biosimilars.},
}

@article {pmid41705769,
year = {2026},
author = {Huang, L and Cong, L and Grzybowski, A},
title = {Tobacco-Attributable Age-Related Macular Degeneration Vision Impairment in Japan: A National and Prefecture-Level Analysis From 1990 to 2040.},
journal = {Translational vision science & technology},
volume = {15},
number = {2},
pages = {23},
doi = {10.1167/tvst.15.2.23},
pmid = {41705769},
issn = {2164-2591},
mesh = {Humans ; Japan/epidemiology ; *Macular Degeneration/epidemiology/etiology ; Male ; Female ; Aged ; Prevalence ; Disability-Adjusted Life Years ; *Vision Disorders/epidemiology/etiology ; Aged, 80 and over ; Middle Aged ; Cost of Illness ; Global Burden of Disease ; },
abstract = {PURPOSE: This study aimed to analyze the spatiotemporal burden of vision impairment due to age-related macular degeneration (AMD) in Japan from 1990 to 2021, projecting to 2040.

METHODS: Using data from the Global Burden of Disease (GBD) study, we systematically analyzed the prevalence, disability-adjusted life years (DALYs), and temporal trends of vision impairment due to AMD in Japan from 1990 to 2021 and projected disease burden to 2040. We also quantified the burden of vision impairment due to AMD attributable to tobacco.

RESULTS: From 1990 to 2021, the number of AMD-related vision impairment cases increased by 159% to 93,310 (95% uncertainty interval [UI], 78,103-112,033); DALYs increased by 134% to 8907 (95% UI, 5984-12,298). However, the age-standardized prevalence rates declined from 22.3 to 19.73 per 100,000, and DALY rates decreased from 2.34 to 1.94. Prevalence was slightly higher in females, although the DALY rate difference was minimal. Burden disparities across all 47 prefectures were small. The contribution of tobacco to age-standardized DALYs decreased by 36.3%. Projections to 2040 estimate a 42.51% increase in total cases, with a rise in the age-standardized prevalence rate among males but a decline continuing among females.

CONCLUSIONS: Despite an increase in absolute cases, age-standardized rates of AMD-related vision impairment in Japan declined from 1990 to 2021, likely due to universal health insurance coverage and effective tobacco control policies. This supports ongoing investment to alleviate the burden in an aging society.

TRANSLATIONAL RELEVANCE: Translating 30-year population data, this study shows that tobacco control and healthcare equity reduce AMD-related vision impairment burden, informing vision loss prevention in aging societies.},
}

Humans
Japan/epidemiology
*Macular Degeneration/epidemiology/etiology
Male
Female
Aged
Prevalence
Disability-Adjusted Life Years
*Vision Disorders/epidemiology/etiology
Aged, 80 and over
Middle Aged
Cost of Illness
Global Burden of Disease

@article {pmid41704651,
year = {2026},
author = {Wong, MW and Li, H and Dan, YS and Lor, SC and Soh, R and Hoang, QV and Chong, RS},
title = {Associations between Intraocular Pressure or Glaucoma Medication with Axial Length and Pathologic Myopia Incidence and Progression.},
journal = {Ophthalmology science},
volume = {6},
number = {3},
pages = {101061},
pmid = {41704651},
issn = {2666-9145},
abstract = {OBJECTIVE: To investigate the relationship between intraocular pressure (IOP) and antiglaucoma medications on both the incidence and progression of myopic macular degeneration (MMD), posterior staphyloma and axial length (AXL) elongation in highly myopic (HM) eyes.

DESIGN: A retrospective multiethnic cohort study with cross-sectional and longitudinal analyses.

Nine hundred eighty-eight HM eyes from 518 multi-ethnic subjects assessed at the Singapore National Eye Centre (2017-2022). Eyes with glaucoma or on existing IOP-lowering therapy were excluded from the primary analyses. Secondary cross-sectional and longitudinal analyses included eyes with glaucoma to explore medication effects.

METHODS: Intraocular pressure was measured with noncontact tonometry. Logistic and linear regression models assessed associations between IOP and MMD/staphyloma presence and progression and AXL elongation. Multivariate analysis was performed to identify independent predictors of progression, including effects of antiglaucoma medication use.

MAIN OUTCOME MEASURES: Presence and progression of MMD and staphyloma, current AXL, and AXL elongation as determined by imaging and clinical examination. Progression was defined by changes in MMD grade, atrophic lesions, or structural staphyloma features over time.

RESULTS: In nonglaucomatous eyes, IOP was not significantly associated with the presence or progression of MMD, staphyloma, or AXL (all P > 0.05). Across all eyes, longer AXL was correlated with earlier spectacle onset, worse visual acuity, longer anterior chamber depth, presence of tilted disc, superior peripapillary atrophy, vitreomacular traction, staphyloma, epiretinal membrane, dome- or saddle-shaped macula, and lacquer crack (P < 0.05). In longitudinal analyses, baseline glaucoma medication use was significantly associated with reduced AXL elongation over time (β = -0.077, P = 0.036), independent of IOP, whereas tilted disc and staphyloma presence predicted greater elongation (P < 0.05). Myopic macular degeneration and staphyloma progression were primarily associated with structural factors, including presence of sloped fovea, macular retinoschisis, epiretinal membrane, and dome- or saddle-shaped macula at baseline (P < 0.05).

CONCLUSIONS: Intraocular pressure was not associated with pathologic myopia-related structural changes or AXL in HM eyes. In contrast, use of antiglaucoma medications was associated with reduced AXL elongation. These findings suggest the potential for IOP-independent pharmacologic modulation of AXL in HM eyes.

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

@article {pmid41703599,
year = {2026},
author = {Yu, J and Zhang, Y and Gao, YL and Xu, JM and Chen, H and Ho, M and Kam, KW and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Metabolic vulnerability index and MetaboHealth score as risk factors for age-related macular degeneration in a large-scale prospective cohort.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-07863-2},
pmid = {41703599},
issn = {1479-5876},
}

@article {pmid41703248,
year = {2026},
author = {Viggiano, P and Borrelli, E and Giannaccare, G and Reibaldi, M and Boscia, F},
title = {Response to: 'Comment on: 'Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results".},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41703248},
issn = {1476-5454},
}

@article {pmid41703247,
year = {2026},
author = {Lolli, I and Pignataro, MG and Termite, AC and Ribezzi, G and Boscia, G and Borrelli, E and Reibaldi, M and Alessio, G and Boscia, F and Viggiano, P},
title = {The progressive journey of poor-responder neovascular AMD: tracking structural evolution and visual decline over time.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41703247},
issn = {1476-5454},
abstract = {PURPOSE: To characterise the natural history of poor-responder neovascular age-related macular degeneration (AMD) by tracking structural evolution and visual decline over time.

METHODS: This retrospective longitudinal study analysed 70 eyes of 70 treatment-naive neovascular AMD patients who completed loading dose therapy, received ≥7 injections in the first year, and experienced ≥10 ETDRS letter visual acuity (BCVA) loss from post-loading baseline. Spectral-domain OCT imaging and BCVA were evaluated at three timepoints: baseline (post-loading), 10-letter loss, and worst visual outcome. Multivariate regression analysis identified independent predictors of visual acuity at each timepoint. Primary structural parameters assessed included macular atrophy, subretinal fibrosis, external limiting membrane (ELM) and ellipsoid zone (EZ) integrity, central retinal thickness (CRT), and fluid parameters.

RESULTS: Mean follow-up was 38.5 ± 22.8 months. Macular atrophy progression was dramatic (7.1% → 41.4% → 81.4%, p < 0.001) and subretinal fibrosis increased substantially (11.4% → 25.7% → 57.1%, p < 0.001). CRT showed paradoxical biphasic evolution (262.6 → 278.6 → 252.0 μm). Multivariate analysis revealed three distinct phases: no independent predictors at baseline, comprehensive multi-pathway model at 10-letter loss with subretinal fibrosis (β = -0.536), hyperreflective material (β = -0.350), and intraretinal fluid (β = -0.223) as independent predictors (R² = 0.428), and fibrotic dominance at worst outcome where subretinal fibrosis emerged as the sole predictor (β = -0.469, R² = 0.220). CRT showed no predictive value across all timepoints.

CONCLUSIONS: Poor-responder neovascular AMD follows a three-phase evolutionary journey with subretinal fibrosis as the dominant independent predictor of visual decline. These findings demand a paradigmatic shift toward qualitative structural assessment focusing on fibrotic changes rather than thickness-based monitoring.},
}

@article {pmid41703113,
year = {2026},
author = {Frank-Publig, S and Buehl, W and Mares, V and Fuchs, P and Coulibaly, LM and Eidenberger, A and Scheschy, U and Faustmann, G and Gumpinger, M and Sükei, E and Bogunovic, H and Reiter, GS and Sacu, S and Schmidt-Erfurth, U},
title = {Artificial Intelligence-based characterization of therapeutic response in fluid types and volumes influencing retinal function in neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-40138-w},
pmid = {41703113},
issn = {2045-2322},
}

@article {pmid41701438,
year = {2026},
author = {Zhang, X and Liu, ZL and Lin, X and Sun, SN and Shi, D and Tian, L and Li, Y and Jin, ZB},
title = {Wnt signaling dysregulation drives Stargardt disease pathogenesis.},
journal = {Science China. Life sciences},
volume = {},
number = {},
pages = {},
pmid = {41701438},
issn = {1869-1889},
abstract = {Stargardt disease, the most common inherited juvenile macular degeneration, is primarily caused by ABCA4 mutations, yet the cellular origin of pathology remains debated. Here, we identify a critical role for Wnt signaling dysregulation, specifically non-canonical Wnt pathway suppression, in driving retinal pigment epithelium (RPE) dysfunction as a central mechanism of disease. Using patient-derived iPSC-RPE harboring distinct ABCA4 mutations, we demonstrate that ABCA4 loss disrupts RPE hexagonal morphology, reduces pigmentation, and aberrantly activates neural retinal differentiation. Mechanistically, transcriptomic and functional analyses revealed pronounced downregulation of non-canonical Wnt signaling (e.g., Wnt5a), which correlated with epithelial disorganization and ectopic neurogenesis. Notably, while canonical Wnt activation failed to rescue these pathological defects, pharmacological stimulation of non-canonical Wnt signaling restored RPE integrity and suppressed neural transdifferentiation in a mutation-dependent manner. These findings not only redefine ABCA4 as a regulator of epithelial Wnt crosstalk but also unveil a divergence in Wnt pathway vulnerability among patients. Our work positions non-canonical Wnt agonism as a therapeutic strategy for Stargardt and underscores the broader imperative for mutation-tailored interventions in inherited retinal diseases. By revealing phenotypic convergence on Wnt signaling dysregulation in ABCA4-deficient RPE, this study provides a framework for understanding epithelial-pathway-driven degeneration, with implications for AMD, fibrosis, and developmental disorders characterized by polarity loss.},
}

@article {pmid41397462,
year = {2026},
author = {Liesenhoff, C and Krause, D and Eckardt, F and Lorger, A and Meyrl, C and Deiters, V and Hafner, M and Schiefelbein, J and Klaas, J and Schworm, B and Priglinger, SG and Siedlecki, J},
title = {Efficacy of 2 mg vs. High-Dose 8 mg Aflibercept in Neovascular Age Related Macular Degeneration.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {243},
number = {2},
pages = {103-109},
doi = {10.1055/a-2760-5850},
pmid = {41397462},
issn = {1439-3999},
mesh = {Humans ; *Recombinant Fusion Proteins/administration & dosage ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage ; Female ; Male ; Aged ; Treatment Outcome ; Dose-Response Relationship, Drug ; Visual Acuity/drug effects ; *Wet Macular Degeneration/drug therapy/diagnosis ; Aged, 80 and over ; Intravitreal Injections ; Angiogenesis Inhibitors/administration & dosage ; },
abstract = {PURPOSE: To investigate the efficacy of switching treatment from 2 mg aflibercept to high-dose 8 mg aflibercept in neovascular age-related macular degeneration (nAMD).

METHODS: The database was screened for eyes with nAMD switched from 2 mg to 8 mg aflibercept. Demographic data, multimodal imaging, treatment parameters and outcomes were recorded. Efficacy of 2 mg vs. 8 mg aflibercept was compared four injections prior to, and four injections after switching by analysing central subfield thickness (CST), subretinal fluid (SRF) and intraretinal fluid (IRF) as well as visual acuity (VA).

RESULTS: Sixteen consecutive eyes of 16 patients (mean age 78.5 ± 5.5 years) were identified. There were 13 women (81.3%) and 3 men (18.7%). Prior to switching, mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 8.1 ± 2.1 years and pretreatment amounted to a mean of 27.8 ± 23.6 injections. Mean injection intervals were similar prior to and after switching (5.05 vs. 5.13 weeks; p = 0.76). CST remained stable before and after switching (p = 0.25). After switching, the percentage of eyes with a dry macula increased from 0% to 37.5% (p = 0.02) and the percentage of eyes with SRF decreased from 93.8% to 56.3% (p = 0.037). There was a trend, but no significant effect towards a reduction of IRF (18.8% to 6.3%, p = 0.60). Visual acuity remained stable irrespective of treatment (p = 0.78).

CONCLUSIONS: Concerning CST on OCT, no clear advantage of high-dose 8 mg aflibercept over conventional 2 mg aflibercept was seen in this study. However, with high-dose 8 mg aflibercept the number of eyes with a dry macula increased, and the amount of eyes with SRF decreased significantly. In pretreated eyes, the analysis of macular fluid compartments (as compared to CST) might be more sensitive for comparing treatment effects between 2 mg and 8 mg aflibercept.},
}

Humans
*Recombinant Fusion Proteins/administration & dosage
*Receptors, Vascular Endothelial Growth Factor/administration & dosage
Female
Male
Aged
Treatment Outcome
Dose-Response Relationship, Drug
Visual Acuity/drug effects
*Wet Macular Degeneration/drug therapy/diagnosis
Aged, 80 and over
Intravitreal Injections
Angiogenesis Inhibitors/administration & dosage

@article {pmid41701337,
year = {2026},
author = {Gilead, N and Chong, YJ and Lim, J and Teo, KYC and Ohno-Matsui, K and Cheung, CMG},
title = {ROLE OF INFLAMMATION IN ATROPHY DEVELOPMENT AND PROGRESSION IN PATHOLOGIC MYOPIA.},
journal = {Retina (Philadelphia, Pa.)},
volume = {46},
number = {3},
pages = {465-476},
doi = {10.1097/IAE.0000000000004697},
pmid = {41701337},
issn = {1539-2864},
mesh = {Humans ; Retrospective Studies ; Male ; Female ; Disease Progression ; *Myopia, Degenerative/diagnosis/physiopathology/complications ; Atrophy/etiology ; *Tomography, Optical Coherence/methods ; Middle Aged ; Aged ; Fluorescein Angiography/methods ; Follow-Up Studies ; Inflammation ; Visual Acuity ; Fundus Oculi ; Adult ; },
abstract = {PURPOSE: To describe the progression of atrophy in pathologic myopia eyes with prior retinal inflammatory lesions consistent with punctate inner choroidopathy.

METHODS: Retrospective case series of 21 eyes with pathologic myopia and resolved retinal inflammatory lesions compared with 26 noninflamed controls (14 fellow eyes; 12 external myopic eyes with pre-existing patchy atrophy). The primary outcome was annual atrophy-area change (mm2/year) on multimodal imaging. Secondary outcomes included incident/enlarging atrophy, multifocal versus unifocal appearance, and META-PM category progression. Group comparisons used Welch t tests and Fisher exact tests; an age-adjusted linear regression examined independent associations.

RESULTS: Over 5.2 ± 3.2 years in inflamed eyes and 5.3 ± 2.4 years in controls, patchy atrophy progressed faster with inflammation (0.76 ± 0.67 vs. 0.38 ± 0.47 mm2/year; P = 0.03). Among eyes starting in myopic macular degeneration Category 1 to 2, incident atrophy occurred in 14 of 14 (100%) inflamed versus 4 of 11 (36.4%) controls (P < 0.01). Overall atrophy activity (new or enlarging) was 21 of 21 (100%) in inflamed eyes versus 19 of 26 (73.1%) controls (P < 0.01). Multifocal atrophy was more frequent with inflammation (15/21, 71.4%) than in controls (6/26, 23.1%; P < 0.01). In age-adjusted regression, inflammation remained independently associated with faster atrophy expansion (β = 0.41 mm2/year; 95% CI, 0.04-0.78; P = 0.033).

CONCLUSION: In pathologic myopia, prior retinal inflammation is independently associated with more frequent multifocal involvement, higher risk of incident atrophy, and a substantially faster atrophy-expansion. Beyond mechanical factors, inflammation seems to be a key driver of atrophic progression in this population.},
}

Humans
Retrospective Studies
Male
Female
Disease Progression
*Myopia, Degenerative/diagnosis/physiopathology/complications
Atrophy/etiology
*Tomography, Optical Coherence/methods
Middle Aged
Aged
Fluorescein Angiography/methods
Follow-Up Studies
Inflammation
Visual Acuity
Fundus Oculi
Adult

@article {pmid41700798,
year = {2026},
author = {Trinh, M and Borrelli, E and Reibaldi, M and Foti, C and Nivison-Smith, L},
title = {Inner Retinal Reflectivity Loss and Concurrent Thickening Predict Short-Term Conversion to Neovascular AMD.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {2},
pages = {34},
doi = {10.1167/iovs.67.2.34},
pmid = {41700798},
issn = {1552-5783},
mesh = {Humans ; Retrospective Studies ; Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; *Retinal Ganglion Cells/pathology ; Case-Control Studies ; *Wet Macular Degeneration/diagnosis ; Nerve Fibers/pathology ; Aged, 80 and over ; Disease Progression ; Visual Acuity ; Middle Aged ; Follow-Up Studies ; *Retina/pathology ; },
abstract = {PURPOSE: To examine inner retinal changes preceding conversion from intermediate age-related macular degeneration (iAMD) to exudative neovascular AMD (nAMD), using topographic optical coherence tomography (OCT) reflectivity and thickness analysis.

METHODS: This retrospective case-control study included 60 individual eyes with iAMD (30 converters and 30 non-converters to nAMD within 1 year). Baseline macular OCT scans were segmented for the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL). Raw linear reflectivity (normalized against vitreous intensity) and thickness were extracted from 48 × 48 grids. Primary outcomes were differences in reflectivity (%) and thickness (µm) between converters and non-converters, adjusted for person-level factors. Secondary outcomes examined retinal macrovascular metrics and odds of conversion (odds ratios [ORs]), further adjusted for traditional AMD factors.

RESULTS: Converters showed global reductions in reflectivity across the RNFL (-6.24%), GCL (-2.01%), and IPL (-1.58%), with modest RNFL thickening (4.48 µm). Topographic analyses revealed nasal reflectivity loss in all layers and localized thickening in the nasal RNFL and paracentral GCL/IPL (P < 0.0001). Macrovascular metrics did not differ between groups. Global and topographic reflectivity loss strongly predicted conversion (univariable ORs up to 1.85 per 1% decrease; 95% confidence interval [CI], 1.38-2.72). RNFL thickening was also predictive (univariable ORs up to 1.64 per 1-µm increase; 95% CI, 1.25-2.32). Both metrics remained significant in multivariable models, whereas drusen volume, pigmentary abnormalities, and fellow-eye status did not.

CONCLUSIONS: Inner retinal reflectivity loss with mild thickening is a strong predictor of short-term progression to nAMD. These OCT-derived biomarkers showed stronger associations with conversion than traditional risk factors and may improve short-term risk stratification and monitoring.},
}

Humans
Retrospective Studies
Tomography, Optical Coherence/methods
Male
Female
Aged
*Retinal Ganglion Cells/pathology
Case-Control Studies
*Wet Macular Degeneration/diagnosis
Nerve Fibers/pathology
Aged, 80 and over
Disease Progression
Visual Acuity
Middle Aged
Follow-Up Studies
*Retina/pathology

@article {pmid41699987,
year = {2026},
author = {Li, ZY and Yang, D and Huang, Y and Li, Y and Zhao, T and Xu, Y},
title = {Dynamin-Related Protein 1-Dependent Disruption of Mitochondrial Homeostasis Drives Blue Light-Induced Epithelial-Mesenchymal Transition in Retinal Aging.},
journal = {Aging cell},
volume = {25},
number = {2},
pages = {e70416},
doi = {10.1111/acel.70416},
pmid = {41699987},
issn = {1474-9726},
support = {#2023A1515012397//Natural Science Foundation of Guangdong Province/ ; #2023A03J0899//Guangzhou Science and Technology Projects/ ; },
mesh = {*Epithelial-Mesenchymal Transition/radiation effects ; Animals ; Humans ; *Dynamins/metabolism ; *Mitochondria/metabolism/radiation effects ; Mice ; *Homeostasis/radiation effects ; *Light/adverse effects ; *Retinal Pigment Epithelium/metabolism/pathology ; Mitochondrial Dynamics/radiation effects ; *Retina/pathology/metabolism/radiation effects ; *Aging ; Macular Degeneration/pathology/metabolism ; Oxidative Stress ; Blue Light ; },
abstract = {Age-related macular degeneration (AMD) stands as a leading cause of blindness in the elderly, yet the fundamental aging processes that underpin its pathogenesis remain incompletely defined. The dysfunction of retinal pigment epithelial (RPE) cells is a central event in AMD, a process that shares key hallmarks with broader cellular aging, particularly the progressive decline in mitochondrial function. In this study, we investigated how a common environmental stressor-blue light-triggers a key pathological transformation, epithelial-mesenchymal transition (EMT), in RPE cells by specifically disrupting mitochondrial dynamics, a core pillar of cellular aging. Using an in vitro model of human RPE cells, we demonstrated that blue light exposure induces a marked shift in mitochondrial dynamics towards excessive fission. This imbalance directly resulted in mitochondrial dysfunction, elevated oxidative stress, and served as the critical driver for the initiation of EMT. Importantly, pharmacological inhibition of the mitochondrial fission GTPase Dynamin-related protein 1 (Drp1) with Mdivi-1 effectively restored mitochondrial network homeostasis, rescued mitochondrial function, and fully reversed the EMT phenotype. These findings were corroborated in a mouse model of blue light-induced retinal damage, where Drp1 inhibition successfully preserved retinal light responses, mitigated structural degeneration, and slowed disease progression. Our study demonstrates that Drp1-mediated excessive mitochondrial fission drives EMT in RPE cells under blue light, linking this mechanism to AMD progression. Consequently, targeting mitochondrial dynamics to maintain cellular homeostasis emerges as a promising and broadly applicable geroscience-based strategy for mitigating age-related tissue dysfunction.},
}

*Epithelial-Mesenchymal Transition/radiation effects
Animals
Humans
*Dynamins/metabolism
*Mitochondria/metabolism/radiation effects
Mice
*Homeostasis/radiation effects
*Light/adverse effects
*Retinal Pigment Epithelium/metabolism/pathology
Mitochondrial Dynamics/radiation effects
*Retina/pathology/metabolism/radiation effects
*Aging
Macular Degeneration/pathology/metabolism
Oxidative Stress
Blue Light

@article {pmid41699888,
year = {2026},
author = {Samoila, L and Farcasanu, A and Simon, S and Bodoki, E and Samoila, O and Vostinaru, O and Dinte, E and Bodoki, AE and Iudean, D and Muresan, C and Clichici, S},
title = {Noninvasive 11.7-T Magnetic Resonance Spectroscopy and Imaging Reveals Retinal Metabolic Alterations Induced by Blue Light Exposure.},
journal = {NMR in biomedicine},
volume = {39},
number = {3},
pages = {e70240},
doi = {10.1002/nbm.70240},
pmid = {41699888},
issn = {1099-1492},
support = {352/390028/23.09.2021//Romanian Ministry of European Investment and Projects (MIPE)/ ; G-2024-71962/23.10.2024//Romanian Ministry of European Investment and Projects (MIPE)/ ; 390005/23.10.2024//Ministry of Research, Innovation and Digitalization (MCID)/ ; },
mesh = {Animals ; *Retina/metabolism/radiation effects/diagnostic imaging ; *Light ; Male ; Rats ; Magnetic Resonance Spectroscopy/methods ; Oxidative Stress/radiation effects ; *Proton Magnetic Resonance Spectroscopy ; Blue Light ; },
abstract = {The eye is a complex structure, with multiple systems involved in focusing and detecting light. Among them, the retina, an integral component of the central nervous system, is considered the most vital and exhibits the highest metabolic activity among all tissues in the human body. It interacts with light, and excessive exposure, especially to blue light, is prone to produce degeneration, mainly through oxidative reactions. This mechanism is involved in age-related macular degeneration or diabetic retinopathy. Animal research is important, considering the high prevalence of these diseases; yet noninvasive procedures involving this research are lacking so far. Our objective was to apply an animal model of oxidative stress and monitor the metabolic changes using 11.7-T [1]H-magnetic resonance spectroscopy ([1]H-MRS). We exposed adult rats to high intensity blue light, at 440 nm (6000 lx) and investigated retinal metabolic changes up to 48 h post exposure. The acquired spectrum highlighted the presence of several essential retinal metabolites, including lipids (alkyl chain CH2), lactate, N-acetylaspartate (NAA), glutamate (Glu), choline (Cho), taurine (Tau), creatine (Cre), and glucose (Glc). Blue light induced specific changes, relatable to oxidative stress, and [1]H-MRS allowed us to follow the dynamic metabolic changes post exposure. This is the first in vivo spectroscopic study of the retinal tissue in which no animals were sacrificed. To validate the in vivo metabolite assignments, localized ex vivo [1]H-MRS was performed on eyes from separate animals that had not been exposed to blue light.},
}

Animals
*Retina/metabolism/radiation effects/diagnostic imaging
*Light
Male
Rats
Magnetic Resonance Spectroscopy/methods
Oxidative Stress/radiation effects
*Proton Magnetic Resonance Spectroscopy
Blue Light

@article {pmid41699676,
year = {2026},
author = {Yang, H and Liu, B and Zhang, Y and Zhang, Z and Tan, H and Li, X},
title = {Caffeine intake and late dry age-related macular degeneration: tea's protective role-insights from NHANES and Mendelian randomization.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00813-6},
pmid = {41699676},
issn = {2056-9920},
support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; },
abstract = {BACKGROUND: Although caffeine is widely consumed and has demonstrated neuroprotective effects, its role in age-related macular degeneration (AMD) remains unclear, particularly across disease subtypes and dietary sources such as tea and coffee.

METHODS: We analyzed 2005-2008 NHANES data using weighted logistic regression and restricted cubic splines to assess the dose-response relationship between caffeine intake and the prevalence of early and late AMD. Two-sample Mendelian randomization (MR) using GWAS summary statistics was employed to evaluate causal effects of tea and coffee consumption on AMD subtypes. Furthermore, a two-step MR approach was utilized to identify potential immune-mediated pathways.

RESULTS: NHANES data showed that caffeine intake was inversely associated with late AMD (fully adjusted OR = 0.65, 95% CI: 0.44-0.96). Dose-response modeling revealed an L-shaped nonlinear relationship (P for nonlinear = 0.046), indicating that the protective effect of caffeine plateaued once daily intake exceeded approximately 110-150 mg. MR analysis further supported a causal protective association between tea consumption and dry AMD, including geographic atrophy (OR = 0.44, 95% CI: 0.20-0.97), which may be partially attributable to immunological mechanisms, specifically the downregulation of secretory regulatory T cells (% of CD4 + Tregs) and CD45RA- CD4 + T cell (% of CD4 + T cell). In contrast, coffee consumption showed no significant effect.

CONCLUSIONS: Tea, a specific source of caffeine typically corresponding to moderate intake levels, may confer protection against dry AMD, including geographic atrophy, potentially through modulation of immune cell profiles. These findings suggest a potential preventive strategy and warrant further clinical investigation.},
}

@article {pmid41697345,
year = {2026},
author = {Fukuda, Y and Notomi, S and Shiose, S and Maehara, Y and Yuge, K and Kiyohara, K and Yasaka, Y and Mori, K and Ishikawa, K and Murakami, Y and Sonoda, KH},
title = {Wide-field choroidal thickness changes after loading-phase anti-VEGF therapy in treatment-naïve neovascular AMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41697345},
issn = {1435-702X},
support = {JP24KJ1780//Japan Society for the Promotion of Science/ ; JP25K12836//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: While it is known that anti-vascular endothelial growth factor (anti-VEGF) treatment for neovascular age-related macular degeneration (nAMD) leads to a reduction in choroidal thickness in the macula, changes in peripheral choroidal thickness remain unclear. This study aimed to evaluate choroidal thickness changes following three monthly intravitreal injections of aflibercept and faricimab in treatment-naïve nAMD.

METHODS: Treatment-naïve nAMD patients receiving three consecutive monthly injections as the loading phase were enrolled in this study. Wide-field swept-source OCT was used to quantify regional choroidal thickness. In the 1:1 propensity score matching, sex, age, baseline best-corrected visual acuity, axial length, and nAMD subtypes were selected as covariates.

RESULTS: A total of 142 eyes from 142 patients were included, with 71 eyes receiving aflibercept and 71 eyes receiving faricimab. Significant reductions in choroidal thickness were observed in both central and peripheral areas, with the most pronounced changes occurring in the central 3 mm-subfield. After propensity score matching, choroidal thickness change rates were compared between the two drug groups. In the central 3 mm-subfield, aflibercept was associated with a significantly greater reduction in choroidal thickness compared with faricimab. No significant differences were observed in other subfields.

CONCLUSION: This study highlights the importance of considering both central and peripheral choroidal changes when evaluating the impact of different anti-VEGF therapies in nAMD.},
}

@article {pmid41694669,
year = {2026},
author = {Reinisalo, M and Helisalmi, S and Koskela, A and Küblbeck, J and Liukkonen, M and Mutikainen, M and Cree, AJ and Griffiths, H and Papp, A and Seitsonen, S and Immonen, I and Soininen, H and Urtti, A and Hiltunen, M and Winiarczyk, M and Resch, M and Ratnayaka, JA and Lotery, AJ and Kaarniranta, K and Honkakoski, P},
title = {Functional polymorphisms in pigmentation-related genes MC1R and DCT display population-specific association with wet age-related macular degeneration.},
journal = {Biochemistry and biophysics reports},
volume = {45},
number = {},
pages = {102477},
pmid = {41694669},
issn = {2405-5808},
abstract = {Age-related macular degeneration (AMD) is among the leading causes of vision loss. Factors increasing the risk of AMD include aging, smoking, cardiovascular diseases and heritability. Although melanin pigment is known to protect retinal homeostasis, the link between pigmentation-related genes and AMD is unclear. We investigated associations between 26 variations in six pigmentation-related genes and wet AMD risk in a Finnish population, followed by replication in the United Kingdom (UK), Hungarian and Polish cohorts, totaling 775 patients and 959 controls. Associations of genetic components with smoking and body mass index (BMI) were tested in the Finnish and UK cohorts. The functionality of candidate variants in human retinal pigment epithelial (RPE) cells was evaluated using gene promoter analysis and gene silencing. Non-coding variants, rs1407995 in the dopachrome tautomerase (DCT) intron and rs3212351 in the melanocortin-1 receptor (MC1R) promoter, were associated with wet AMD in the Finnish cohort. The variant rs3212351 disrupts a binding site for transcription factor MITF and reduces MC1R expression in RPE cells. Unlike in the Finnish cohort, the data regarding the MC1R variant suggested a protective association in the Polish cohort. The incidence of AMD increased with age in all cohorts. Smoking increased AMD risk in the cohorts studied. Sex and BMI showed no associations. These findings suggest that variations in DCT and MC1R genes known to affect skin and eye pigmentation may also play a role in development of wet AMD. The observed population differences may be related to variable pigmentation traits.},
}

@article {pmid41694267,
year = {2026},
author = {Pan, L and Deng, J and Yang, J and Wang, M and Chen, Z and Wang, T and Li, Y},
title = {Causal effects of antibody-mediated immunity to pathogens on five ophthalmic diseases: a Mendelian randomization study.},
journal = {Experimental biology and medicine (Maywood, N.J.)},
volume = {251},
number = {},
pages = {10906},
pmid = {41694267},
issn = {1535-3699},
mesh = {Humans ; Mendelian Randomization Analysis ; *Eye Diseases/immunology/genetics ; Polymorphism, Single Nucleotide ; Genome-Wide Association Study ; },
abstract = {While immune responses related to infections have been linked to ocular diseases, their causal role remains to be established. This study aimed to assess the causal relationship between antibody-mediated immune responses to infectious agents and five ocular conditions: chronic iridocyclitis (CIR), scleritis, wet age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma. We performed a two-sample Mendelian randomization (MR) analysis using GWAS data to assess causality between antibody responses to 46 pathogens and five ophthalmic diseases. The instrumental variables were Single nucleotide polymorphisms (SNPs). Causal estimates were primarily generated via the inverse-variance weighted method, supplemented by MR-Egger and weighted median methods. A Bonferroni-corrected threshold of P < 2.17 × 10[-4] was applied. Sensitivity analyses included Cochran's Q, MR-Egger, and MR-PRESSO for heterogeneity and pleiotropy. Reverse MR was performed to assess bidirectionality. Forward MR identified causal effects of infection-induced immune responses on ocular diseases. Epstein-Barr virus (EBV) ZEBRA antibodies were positively correlated with CIR, whereas Varicella zoster virus glycoproteins E and I antibodies were associated with scleritis and DR as risk factors. Genetically predicted anti-polyomavirus 2 IgG seropositivity (JCV IgG+) was identified as a risk factor for DR, wet AMD and glaucoma. In contrast, The EBV EBNA-1 antibody is associated with DR, wet AMD, and glaucoma as a protective factor, whereas the EBV VCA18 antibody is negatively associated with wet AMD. Reverse MR analysis indicated that DR may elevate JCV VP1 antibody levels. This study provides the first genetic evidence of a causal link between pathogen-specific immune responses and ocular diseases, offering a foundation for targeted immunomodulatory and personalized therapies.},
}

Humans
Mendelian Randomization Analysis
*Eye Diseases/immunology/genetics
Polymorphism, Single Nucleotide
Genome-Wide Association Study

@article {pmid41694220,
year = {2026},
author = {Li, J and Ma, Y and Hu, M and Zhang, Q and Wang, A and Tang, Q and Guo, Q and Huang, B},
title = {PANoptosis-Related Diagnostic Biomarkers in Non-Neovascular Age-Related Macular Degeneration: An Integrative Transcriptomic and Experimental Study.},
journal = {Genetics research},
volume = {2026},
number = {},
pages = {8903808},
pmid = {41694220},
issn = {1469-5073},
mesh = {Humans ; Animals ; *Macular Degeneration/genetics/diagnosis/pathology ; *Transcriptome/genetics ; Mice ; Biomarkers/metabolism ; Retinal Pigment Epithelium/metabolism/pathology ; Gene Expression Profiling ; Female ; Male ; Retina/metabolism/pathology ; },
abstract = {Age-related macular degeneration (AMD), particularly its non-neovascular (dry) form, is a progressive retinal disorder that causes central vision loss and substantial impairment in daily life. Inflammation and immune dysregulation are recognized as core drivers of AMD, yet the contribution of PANoptosis, a form of programmed cell death that integrates pyroptosis, apoptosis, and necroptosis, remains unclear. In this study, we integrated human single-cell transcriptomic and bulk microarray datasets from the retina and retinal pigment epithelium-choroid to characterize PANoptosis-related transcriptional changes in dry AMD. Dimensionality reduction, cell-type annotation, and PANoptosis gene-set scoring revealed a distinct PANoptosis signature enriched in AMD, with particularly strong activation in myeloid populations. By combining differential expression analysis with machine learning-based feature selection, we identified four PANoptosis-related genes (PON2, BNIP3, EPHB6, and TPD52) that robustly distinguished AMD from control samples and were associated with an altered immune microenvironment. Genetic instrument analysis further suggested a positive association between TPD52 expression and AMD risk. At the cellular level, our data highlighted macrophages, especially pro-inflammatory M1-like macrophages, as key coordinators of PANoptosis-related pathways in dry AMD. To validate these findings in vivo, we used a sodium iodate-induced mouse model of dry AMD and observed significant dysregulation of PON2, BNIP3, EPHB6, and TPD52 in the retina by RT-qPCR, consistent with the human transcriptomic results and supporting their involvement in retinal degeneration and inflammation. Together, these findings implicate PANoptosis as an important and previously underappreciated component of dry AMD pathophysiology, define a four-gene PANoptosis-related signature with diagnostic potential, and suggest new molecular targets for therapeutic intervention.},
}

Humans
Animals
*Macular Degeneration/genetics/diagnosis/pathology
*Transcriptome/genetics
Mice
Biomarkers/metabolism
Retinal Pigment Epithelium/metabolism/pathology
Gene Expression Profiling
Female
Male
Retina/metabolism/pathology

@article {pmid41693903,
year = {2026},
author = {Patel, Y and Baumann, B and Merkle, C},
title = {Blood flow analysis of retinal neovascularisations in a VLDLR mouse model using contrast-enhanced optical coherence tomography.},
journal = {Biomedical optics express},
volume = {17},
number = {2},
pages = {991-1010},
pmid = {41693903},
issn = {2156-7085},
abstract = {Age-related macular degeneration (AMD) is a major cause of global blindness that affects millions worldwide. Certain forms of AMD cause neovascularisations (NVs), which form retinal-choroidal anastomoses. This disrupts healthy haemodynamic patterns, and early detection and treatment are crucial for preserving vision. Here, we employ a custom-built optical coherence tomography (OCT) imaging system to investigate these NVs in a very low-density lipoprotein receptor (VLDLR) knockout mouse model. Mice were imaged before, during, and after contrast agent injection, aiming to enhance our understanding of the NV haemodynamics. Doppler signal analysis techniques were employed to calculate flow velocities within individual NVs. Flow rates pre- and post-injection were determined based on these velocity measurements. Particle tracking was performed on two NVs for a comparative analysis with the Doppler velocity measurements. Both methods of measuring flow velocities showed good agreement post-contrast injection. The analysis of post-injection flow rates from the NVs revealed diverse behaviours. Some NVs exhibited stable flow rates over time, while others showed signs of instability, with flow rates changing substantially or even changing flow direction at different time points. Additionally, it was observed at multiple time points that flow from certain NVs moved from the choroid to the retina at the same time that other NVs displayed flow in the opposite direction. These observations suggest complex interactions between choroidal and retinal vascular networks in diseases like AMD. Further characterisation using contrast-enhanced Doppler OCT may improve our understanding of neovascular haemodynamics.},
}

@article {pmid41692377,
year = {2026},
author = {Vidal-Oliver, L and Garzone, D and Schloesser, L and Thiele, S and Pfau, M and Harmening, WM and Ameln, J and Dolz-Marco, R and Cuenca, N and Ortuño-Lizaran, I and Wu, Z and Guymer, RH and Finger, RP},
title = {Structural photoreceptor evaluation in age-related macular degeneration. A comprehensive review of methods and clinical significance.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101447},
doi = {10.1016/j.preteyeres.2026.101447},
pmid = {41692377},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) is a disease that primarily affects the outer retina, with progressive photoreceptor degeneration and atrophy of the retinal pigment epithelium (RPE). Advances in imaging now enable photoreceptor changes to be detected and quantified with unprecedented sensitivity, whereas comparable biomarkers of RPE dysfunction remain less developed. As such, photoreceptor-based biomarkers are increasingly considered potential surrogates for current clinical trial endpoints. This review examines the current imaging modalities-particularly optical coherence tomography (OCT) and modalities enhanced by adaptive optics (AO) -used to evaluate photoreceptor structure in AMD. We explore the intrinsic value of parameters such as outer nuclear layer thickness, external limiting membrane integrity, photoreceptor inner and outer segment thickness, ellipsoid zone (EZ) integrity, and EZ reflectivity on OCT, and cone density and regularity on AO imaging, highlighting their potential and limitations. While OCT-based metrics are the most accessible in clinical settings, their clinical utility is hampered by inconsistent segmentation protocols and methodological heterogeneity. AO imaging offers unmatched resolution but faces practical barriers to widespread adoption. The field is moving in a promising direction with emerging computational tools and artificial intelligence improving accuracy and scalability. However, progress is contingent on establishing consensus definitions, standardized acquisition and analysis protocols, and normative datasets. Future efforts should focus on translating high-resolution imaging into robust, reproducible biomarkers that can be widely adopted in both clinical practice and therapeutic development.},
}

@article {pmid41692319,
year = {2026},
author = {Karami, S and Charpentier, P and Landreville, S and Proulx, S},
title = {Pigment epithelium-derived factor and osteopontin protect retinal pigment epithelial cells from oxidative stress in human primary retinal pigment epithelial cells in 2D and 3D models.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.02.034},
pmid = {41692319},
issn = {1873-4596},
abstract = {Retinal pigment epithelial (RPE) cells are particularly vulnerable to oxidative stress. Neighboring choroidal melanocytes (CMs) secrete trophic factors, such as pigment epithelium-derived factor (PEDF) and osteopontin (OPN), which may mitigate oxidative damage in RPE cells. Herein, we investigated the ability of PEDF and OPN to protect RPE cells from extended NaIO3-induced oxidative stress damage. Primary human RPE cells were seeded on plastic (2D culture) or on a 3D tissue-engineered choroidal stroma (TECS) containing (or not) CMs. PEDF or OPN was added before, during, and after 5 days of NaIO3 exposure. Analyses included assessment of PEDF and OPN expression, intracellular reactive oxygen species (ROS), lipid peroxidation, mitochondrial superoxide, cell death, antioxidant capacity (TAC) and p-Nrf2 nuclear translocation. Adding exogenous PEDF to the growth media stimulated de novo PEDF secretion by RPE cells, whereas OPN concentration detected in the growth media corresponded to the amount added. PEDF and OPN levels were consistently lower in the growth media of 3D TECS compared to the 2D cultures. Oxidative stress significantly increased intracellular ROS, lipid peroxidation, and RPE cell death in both 2D and 3D cultures, which were reduced by PEDF or OPN supplementation. Oxidative stress and PEDF or OPN supplementation did not alter the TAC of RPE cells. PEDF or OPN supplementation promoted p-Nrf2 nuclear translocation in RPE cells on plastic, even without oxidative stress, whereas this response was not observed in 3D TECS cultures. Adding CMs to the 3D TECS did not influence p-Nrf2 nuclear translocation in RPE cells. Overall, PEDF and OPN supplementation significantly protected human RPE cells against NaIO3-induced oxidative stress damage. In 3D TECS, CMs secreted insufficient levels of PEDF and OPN for RPE cells to manage oxidative stress-induced damage. These findings demonstrate that exogenous supplementation with PEDF and OPN proteins may be beneficial for oxidative-stress related eye diseases.},
}

@article {pmid41692264,
year = {2026},
author = {Zhang, Z and Wang, H and Pan, S and Han, W and Liu, M and Chen, Y and Li, X and Zhan, Y and Wu, H and Yao, J and Yang, J and Wu, F},
title = {Enhancing Mouse Fundus Imaging with OCT Embedding Medium: Prolonging Imaging Duration and Improving Image Quality.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110914},
doi = {10.1016/j.exer.2026.110914},
pmid = {41692264},
issn = {1096-0007},
abstract = {Fundus diseases are common and serious ophthalmic conditions, including macular degeneration, diabetic retinopathy, glaucoma, and others, which can lead to severe vision loss. Mice, widely used as experimental animal models, play a crucial role in ophthalmic disease research. However, existing mouse fundus imaging techniques encounter several challenges during prolonged, high-precision imaging, such as corneal whitening, poor optical quality, and motion artifacts. In this study, we propose an innovative method based on an OCT embedding medium that, when applied to the mouse corneal surface, improves the alignment between the eye and the OCT lens. This method effectively reduces stray light (flare)and motion artifacts while slowing corneal dehydration. It significantly enhances the quality of mouse fundus imaging and extends imaging duration, particularly in the age-related macular degeneration (AMD) mouse model, where it improves retinal blood vessel visualization. This approach provides a novel technical solution for ophthalmic research and holds potential for clinical applications.},
}

@article {pmid41692178,
year = {2026},
author = {Yaldo, L and Ngo, A and Yaldo, M and Abdelaal, A and Ong, J and Kiryakoza, L and Sengillo, J},
title = {Obstructive sleep apnea and risk of age-related macular degeneration: A systematic review and meta-analysis.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.02.016},
pmid = {41692178},
issn = {1879-1891},
abstract = {TOPIC: We evaluated whether obstructive sleep apnea (OSA) is associated with an increased risk of age-related macular degeneration (AMD). The population included adults with and without OSA. Outcomes included overall AMD risk and AMD stage-specific outcomes, including neovascular AMD (nAMD), non-neovascular AMD, late AMD with geographic atrophy (GA), and anti-VEGF therapy requirement.

CLINICAL RELEVANCE: AMD is a leading cause of irreversible vision loss worldwide. OSA, characterized by intermittent hypoxia, oxidative stress, and vascular dysregulation, shares key pathogenic mechanisms with AMD. Understanding whether OSA increases AMD risk could help identify high-risk populations for earlier detection, monitoring, and intervention.

METHODS: We conducted a systematic review and meta-analysis of observational studies. PubMed, Web of Science, and Scopus were searched to June 27, 2025, supplemented by Google Scholar and citation tracking. Eligible studies reported AMD outcomes in both OSA and non-OSA groups. Methodological quality was assessed using the National Institutes of Health Quality Assessment Tool. Random-effects models were used to pool odds ratios (ORs) and adjusted hazard ratios (aHRs). Certainty of evidence was evaluated with the GRADE framework. The protocol was registered in PROSPERO (CRD420251119881).

RESULTS: Eight studies (3,536,314 participants; 207,130 with OSA) were analyzed. In crude analyses, OSA was associated with higher odds of AMD (OR=1.45; 95%CI: 1.13-1.84; low certainty) with similar increases for nAMD (OR=1.76; 95%CI: 1.06-2.93; low certainty) and non-neovascular AMD (OR=1.95; 95%CI: 1.04-3.66; low certainty). No significant associations were observed in subgroups without confounder adjustment (low certainty) or with regression adjustment (low certainty), whereas propensity-score matched studies indicated higher odds (OR=1.92; 95%CI: 1.05-3.52; low certainty). Adjusted analyses confirmed the association (aOR=1.44; 95%CI: 1.11-1.77; moderate certainty) with no heterogeneity. Time-to-event analyses showed an increased hazard of AMD (aHR=1.66; 95%CI: 1.13-2.19; low certainty), though stage-specific analyses for neovascular and non-neovascular AMD were not significant (very low certainty).

CONCLUSION: OSA may be associated with an increased risk of AMD, though the certainty of evidence ranges from moderate to very low. Variability in diagnostic criteria for OSA and AMD, high heterogeneity in several analyses, and reliance on observational data limit the strength of inference.},
}

@article {pmid41690011,
year = {2026},
author = {Zhao, P and Ansaripour, R and Singh, D and Rong, G and Young, MJ and Carrier, RL},
title = {Novel explant model for human retinal progenitor cell transplantation.},
journal = {Biochemical and biophysical research communications},
volume = {807},
number = {},
pages = {153432},
doi = {10.1016/j.bbrc.2026.153432},
pmid = {41690011},
issn = {1090-2104},
abstract = {Retinal degenerative diseases, including age-related macular degeneration and retinitis pigmentosa, have led to vision loss for millions worldwide. While stem/progenitor cell transplantation shows promise, its clinical application is limited by poor survival, efflux, and low integration of transplanted cells. Biopolymer scaffolds have been explored to improve viability and differentiation, but most in vitro assessments rely on simplified or endpoint analyses that fail to capture dynamic behaviors. Retinal explant models, which preserve tissue architecture and neuronal connections, provide a more physiologically relevant platform. However, conventional explant models are often limited to endpoint analyses and lack real-time monitoring capabilities. Here, we developed a novel explant model for human retinal progenitor cell (hRPC) transplantation using porcine retinal tissue slice, agarose hydrogel, and confocal microscope with an incubation cage. Retinal tissue slices exhibited comparable viability before and after imaging. Alginate-based hydrogels containing hRPCs were injected adjacent to photoreceptor or ganglion cell layer of cross-sectional retinal tissue slices, enabling visualization of the cells' position relative to retinal tissue slice over time. Real-time confocal imaging tracked key cellular behaviors, including migration, attachment, invasion, viability, and apoptosis. Injected hRPCs displayed random movement within the bulk alginate hydrogel and localized attachment or invasion at the hydrogel-tissue interface. Notably, laminin-incorporated alginate hydrogels promoted cell clustering and facilitated deeper invasion into retinal tissue compared with single cells.},
}

@article {pmid41688763,
year = {2026},
author = {Kim, TH and Kwon, CY and Song, JY and Yoo, HC},
title = {AAV-based gene therapies for neovascular AMD.},
journal = {Gene therapy},
volume = {},
number = {},
pages = {},
pmid = {41688763},
issn = {1476-5462},
support = {RS-2024-00412879//National Research Foundation of Korea (NRF)/ ; 2021R1C1C2006283//National Research Foundation of Korea (NRF)/ ; RS-2024-00403169//Korea Basic Science Institute (KBSI)/ ; 2024//Chung-Ang University (CAU)/ ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision loss in the elderly, driven by choroidal neovascularization and dysregulated vascular endothelial growth factor (VEGF) signaling. While anti-VEGF injections have transformed management, their frequent administration imposes a substantial burden on patients and limits adherence. Adeno-associated virus (AAV)-based gene therapy offers sustained intraocular delivery of anti-angiogenic agents with a single treatment, potentially overcoming these limitations. This review summarizes the rationale for AAV use in ocular gene therapy, compares major delivery routes, and highlights leading clinical candidates, including RGX-314, ADVM-022, 4D-150, and NG101. Advances in vector engineering, promoter optimization, and immune modulation are discussed alongside key challenges such as preexisting immunity and inflammation. Future directions include next-generation capsids, combination regimens, and precision patient selection. Collectively, these developments position AAV-based gene therapy as a promising strategy to redefine the therapeutic landscape of nAMD.},
}

@article {pmid41687799,
year = {2026},
author = {Browning, DJ},
title = {The Trouble with PDT.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.02.002},
pmid = {41687799},
issn = {1879-1891},
abstract = {PURPOSE: To examine the role of photodynamic therapy (PDT) in the treatment of retinal disease and obstacles to use in the United States for evidence-based indications Design: Perspective essay Methods: Historical summary, exemplary case report, and relevant literature review.

RESULTS: PDT has been approved by the Food and Drug Administration for use in neovascular age related macular degeneration (AMD) but has been superseded by anti-vascular endothelial growth factor drugs and is rarely used for this indication. It is regularly used in polypoidal choroidal vasculopathy (PCV) without reimbursement difficulty because PCV is acknowledged to be a form of AMD. It is effective for serous retinal detachment associated with choroidal hemangioma. Because this is rare indication insurers generally authorize its use. It is the most effective treatment for chronic central serous retinopathy (CSR), a relatively common indication, but authorization from insurers is difficult to obtain leading to avoidable loss of vision because patients often will not or cannot pay chargemaster prices. Many retina specialists eschew PDT because the expense in time and the laser does not balance the difficulties with reimbursement and comparative advantage of allocating their time in other ways.

CONCLUSIONS: In the United States, finding a retina specialist who does PDT is challenging for patients with diseases for which it is indicated. Obtaining coverage for CSR is difficult for retina specialists treating patients with CSR in the United States, but not internationally. As a result, delayed or no treatment for cases indicated leads to avoidable loss of vision. A suggested solution is that insurers agree to cover PDT for chronic CSR at a rate equal to 1.3 times Medicare reimbursement for neovascular AMD.},
}

@article {pmid41687798,
year = {2026},
author = {Kikushima, W and Gilead, N and Sherif, MZA and Zhang, C and Jiang, Z and Sun, C and Ong, C and Hong, CH and Teo, KYC and Chakravarthy, U and Cheung, CMG},
title = {Prevalence and associated features of reticular pseudodrusen in neovascular age-related macular degeneration in an Asian population.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.02.011},
pmid = {41687798},
issn = {1879-1891},
abstract = {PURPOSE: To investigate the prevalence and associated features of reticular pseudodrusen (RPD) in an Asian cohort with neovascular age-related macular degeneration (nAMD).

DESIGN: Retrospective, observational, cross-sectional study.

SUBJECTS: A total of 353 patients presenting with treatment naïve unilateral nAMD.

METHODS: Patients presenting with treatment naïve unilateral nAMD who enrolled into the Asian AMD Phenotyping study between 2015 and 2025 were reviewed. All patients underwent protocolized imaging which included color fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein and indocyanine green angiography. Images were evaluated for drusen and RPD was considered present based on SD-OCT. Patients with ungradable eyes due to extensive neovascular changes or poor image qualities were excluded. Baseline characteristics of patients with RPD were compared to those with soft/cuticular or no drusen.

MAIN OUTCOME MEASURES: The prevalence and associated features of RPD. The systemic and ocular parameters were compared among the patients with RPD, soft/cuticular drusen, and no drusen.

RESULTS: Among 353 eligible patients (706 eyes), RPD was found in 68 eyes in 51 patients (9.6% per eye, 14.4% per patient). Patients with RPD were older compared to those with soft/cuticular or no drusen (P=0.0005 and P<0.0001, respectively). Eyes with RPD showed thinner choroidal thickness, and higher prevalence of type 3 macular neovascularization (MNV) (Odds Ratio 6.94, p=0.01) compared to those with soft/cuticular or no drusen.

CONCLUSIONS: This is one of the largest series evaluating the prevalence of RPD in nAMD in Asian population. Our findings suggest that ethnicity mainly impacts the prevalence of RPD. However, among patients with RPD, regardless of their ethnicity, there is a strong association with thin choroid and type 3 MNV.},
}

@article {pmid41687120,
year = {2026},
author = {Nascimento, LM and Louzada, RN and Amaral, DC and Jacometti, R and Viegas Mendonça, VP and Chamis, B and Pereira Gonzalez, JV and Lessa, CT and Ribeiro Monteiro, ML and Ferrara, D},
title = {Associations Between Sleep Disorders and Age-related Macular Degeneration: A Systematic Review and Meta-analysis.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004800},
pmid = {41687120},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the relationship between sleep disorders, including insomnia and obstructive sleep apnea (OSA), personal chronotype, and age-related macular degeneration (AMD).

METHODS: We systematically reviewed articles in PubMed, EMBASE, and Web of Science that provided information on AMD and sleep disorders, whether qualitative or quantitative. We systematically screened the abstracts of potentially eligible studies and subsequently assessed the full-text reports of those deemed relevant in detail. The study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.

RESULTS: Twenty-two studies were included in our final review. OSA was associated with a higher risk of AMD, based on seven studies (HR 1.43; 95% CI 1.14-1.79 p < 0.001; I2 = 96%). The analysis showed a statistically significant association between the morning person chronotype and an increased odds of AMD (OR 1.19; 95% CI 1.10-1.30; p < 0.001; I2 = 0%). We found little to no association between sleep duration and insomnia.

CONCLUSION: Our meta-analyses, although based on a limited number of studies, indicate that sleep disorders, particularly OSA, are associated with increased odds of developing AMD. However, further research is needed to understand how sleep duration affects disease progression and to determine the benefits of treating sleep disorders for AMD.},
}

@article {pmid41686445,
year = {2026},
author = {Hussey, KA and Eldred, KC and Guy, B and Santiago, CP and Zhang, JS and Glass, I and Reh, TA and Blackshaw, S and Goff, LA and Johnston, RJ},
title = {A cell fate specification and transition mechanism for human foveolar cone subtype patterning.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {7},
pages = {e2510799123},
doi = {10.1073/pnas.2510799123},
pmid = {41686445},
issn = {1091-6490},
support = {DGE-1746891//NSF | NSF Graduate Research Fellowship Program (GRFP)/ ; DRG 32-20//Damon Runyon Cancer Research Foundation (DRCRF)/ ; GT15994//HHMI (HHMI)/ ; F31EY033656//HHS | NIH | National Eye Institute (NEI)/ ; R24HD000836//HHS | NIH | Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)/ ; TA-RM-0620-0788-463 UWA//Foundation Fighting Blindness (FFB)/ ; R01EY036173//HHS | NIH | National Eye Institute (NEI)/ ; R01EY031685//HHS | NIH | National Eye Institute (NEI)/ ; R01EY030872//HHS | NIH | National Eye Institute (NEI)/ ; G2019300//BrightFocus Foundation (BFF)/ ; 2022-MSCRFD-5895//Maryland Stem Cell Research Fund (MSCRF)/ ; },
mesh = {Humans ; *Retinal Cone Photoreceptor Cells/metabolism/cytology ; Organoids/metabolism/cytology ; Cell Differentiation ; Signal Transduction ; Retinoic Acid 4-Hydroxylase/metabolism/genetics ; Tretinoin/metabolism ; Retina/metabolism ; Iodide Peroxidase/metabolism/genetics ; },
abstract = {In the central region of the human retina, the high-acuity foveola is notable for its dense packing of green (M) and red (L) cones and absence of blue (S) cones. To identify mechanisms that pattern cones in the foveola, we examined human fetal retinas and differentiated retinal organoids. During development, sparse S-opsin-expressing cones are initially observed in the foveola. Later in fetal development, the foveola contains a mix of cones that either coexpress S- and M/L-opsins or exclusively express M/L-opsin. In adults, only M/L cones are present. Two signaling pathway regulators are highly and continuously expressed in the central retina: Cytochrome P450 26 subfamily A member 1 (CYP26A1), which degrades retinoic acid (RA) and Deiodinase 2 (DIO2), which promotes thyroid hormone (TH) signaling. Both CYP26A1 mutant organoids and high RA conditions increased the number of S cones and reduced the number of M/L cones in retinal organoids. In contrast, sustained TH signaling promoted the generation of M/L-opsin-expressing cones and induced M/L-opsin expression in S-opsin-expressing cones, showing that cone fate is plastic. Our data suggest that CYP26A1 degrades RA to specify M/L cones and limit S cones and that continuous DIO2 expression sustains high levels of TH to transition S-opsin-expressing cones into M/L cone fate, resulting in the foveola containing only M/L cones. Given the vulnerability of the foveola in macular degeneration and other retinal disorders, these findings provide a mechanistic framework for engineering organoids for therapeutic applications.},
}

Humans
*Retinal Cone Photoreceptor Cells/metabolism/cytology
Organoids/metabolism/cytology
Cell Differentiation
Signal Transduction
Retinoic Acid 4-Hydroxylase/metabolism/genetics
Tretinoin/metabolism
Retina/metabolism
Iodide Peroxidase/metabolism/genetics

@article {pmid41683912,
year = {2026},
author = {Rusciano, D and Gagliano, C and Avitabile, A and Maya-Vetencourt, JF},
title = {Targeted RNA Degradation by RIBOTACs: A Novel Therapeutic Avenue for Ophthalmic Diseases.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
pmid = {41683912},
issn = {1422-0067},
mesh = {Humans ; Animals ; *Eye Diseases/genetics/drug therapy/therapy/metabolism ; *RNA Stability/drug effects ; *Ribonucleases/metabolism ; },
abstract = {Ophthalmic diseases, including inherited retinal dystrophies, age-related macular degeneration (AMD), and glaucomatous neuropathies, are often driven by the expression of pathogenic proteins or dysfunctional non-coding RNAs that are currently considered 'undruggable' with conventional small-molecule therapeutics. The emerging strategy of Ribonuclease-Targeting Chimeras (RIBOTACs) offers a revolutionary approach to address this therapeutic gap. RIBOTACs are heterobifunctional small molecules designed to bind a specific target RNA with one moiety and recruit a latent endogenous ribonuclease, such as RNase L, with the other, thereby catalyzing the RNA's degradation. This targeted degradation can potentially halt the production of mutant proteins, eliminate toxic gain-of-function RNAs, or modulate key regulatory pathways involved in angiogenesis, inflammation, and apoptosis-core processes in many blinding diseases. This review explores the immense potential of applying RIBOTAC technology to ophthalmology, discussing prospective targets such as mutant alleles in retinitis pigmentosa, VEGF transcripts in neovascular AMD, and inflammatory mediators in uveitis. We will also address the unique challenges and opportunities for RIBOTAC development in the eye, including delivery strategies to overcome ocular barriers, the need for high specificity to avoid off-target RNA degradation, and the optimization of pharmacokinetic properties for intraocular administration. With continued innovation, RIBOTACs are poised to evolve into a robust therapeutic platform, expanding the druggable genome and enabling precise, durable treatments for a range of currently intractable ophthalmic conditions.},
}

Humans
Animals
*Eye Diseases/genetics/drug therapy/therapy/metabolism
*RNA Stability/drug effects
*Ribonucleases/metabolism

@article {pmid41684578,
year = {2025},
author = {Tong, L and Zhan, Q and Zhang, L},
title = {Age-related macular degeneration in the context of an update from the Global Burden of Disease Study 2019.},
journal = {Archives of medical science : AMS},
volume = {21},
number = {6},
pages = {2441-2449},
pmid = {41684578},
issn = {1734-1922},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of central vision loss, with an increasing prevalence related to a growing economic burden. Understanding the epidemiological changes of AMD is essential for targeting the resource allocation of medicine, interventions, and the economy.

MATERIAL AND METHODS: The global prevalence and years lived with disability of AMD by sociodemographic index (SDI), sex, and age groups from 1990 to 2019 based on the Global Burden of Disease Study 2019 were retrieved and utilized to estimate epidemiological changes.

RESULTS: The global AMD population increased significantly from 3581.33 thousand in 1990 to 7792.53 thousand in 2019, and the years lived with disability significantly increased from 296.77 thousand years to 564.06 thousand years. The AMD burden was higher among females (57.77% to 59.20%), the elderly (65-74 years old), and individuals in high-middle and middle SDI regions from 1990 to 2019. The most significant increase in global burden occurred between 2014 and 2019. The age-standardized rate was predicted to remain stable, but the AMD case number was predicted to increase over the next 20 years. Tobacco use was the major diminishing risk factor.

CONCLUSIONS: The present study demonstrated the increasing AMD burden in the past 30 years and predicted the increasing change of AMD prevalence in the next 20 years in the context of the aging global population. Disease burdens, including case number and age-standardized rate, were higher among females, the elderly, and individuals in high-middle and middle SDI regions. The present findings will contribute to healthcare investment and policymaking.},
}

@article {pmid41683853,
year = {2026},
author = {Gong, X and Örge, FH},
title = {Glucagon-like Peptide-1 Receptor Agonists and Ocular Disease: Mechanisms, Evidence and Therapeutic Perspectives.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
doi = {10.3390/ijms27031432},
pmid = {41683853},
issn = {1422-0067},
mesh = {Humans ; *Glucagon-Like Peptide-1 Receptor Agonists ; Animals ; *Eye Diseases/drug therapy/metabolism ; Diabetic Retinopathy/drug therapy/metabolism ; Macular Degeneration/drug therapy/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Diabetes Mellitus, Type 2/drug therapy ; Glaucoma/drug therapy/metabolism ; Hypoglycemic Agents/therapeutic use ; },
abstract = {Ocular diseases, including glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD), remain major global causes of irreversible vision loss. Despite advances in clinical management, current therapies insufficiently address the shared metabolic, inflammatory, vascular, and neurodegenerative mechanisms underlying these conditions. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for type 2 diabetes and obesity, have emerged as multi-target candidates for ocular therapeutics due to their pleiotropic anti-inflammatory, antioxidant, vasculoprotective, and neuroprotective properties. Preclinical studies consistently demonstrate that GLP-1RAs preserve blood-retina barrier integrity, suppress pathological angiogenesis, mitigate oxidative and inflammatory stress, and protect retinal neurons from degeneration. Complementary clinical and real-world evidence shows a robust and reproducible reduction in glaucoma risk among GLP-1RA users across diabetic and non-diabetic populations. By contrast, findings for DR and AMD are more heterogeneous and appear context-dependent, with potential benefits most evident in early or non-exudative disease stages. Emerging safety considerations-including reports of nonarteritic anterior ischemic optic neuropathy and early DR worsening in the setting of rapid glycemic improvement-highlight the need for careful interpretation, individualized risk assessment, and appropriate ophthalmic monitoring. This review synthesizes molecular mechanisms, experimental data, clinical and pharmacoepidemiologic evidence, and safety signals to critically evaluate the therapeutic potential of GLP-1RAs in ocular disease. We also outline key translational challenges, including the need for ocular-targeted delivery strategies, prospective ophthalmology-specific trials, and precision-medicine approaches to determine when and how GLP-1RAs can be safely advanced as disease-modifying treatments in ophthalmology.},
}

Humans
*Glucagon-Like Peptide-1 Receptor Agonists
Animals
*Eye Diseases/drug therapy/metabolism
Diabetic Retinopathy/drug therapy/metabolism
Macular Degeneration/drug therapy/metabolism
Glucagon-Like Peptide-1 Receptor/metabolism
Diabetes Mellitus, Type 2/drug therapy
Glaucoma/drug therapy/metabolism
Hypoglycemic Agents/therapeutic use

@article {pmid41683651,
year = {2026},
author = {Chao, WW and Chao, HW and Chao, HM},
title = {Combined Therapy Versus Fortified Anti-VEGF Monotherapy in Type C Polypoidal Choroidal Vasculopathy: Long-Term Outcomes and Exploratory Biomarker Insights.},
journal = {International journal of molecular sciences},
volume = {27},
number = {3},
pages = {},
doi = {10.3390/ijms27031224},
pmid = {41683651},
issn = {1422-0067},
mesh = {Humans ; Male ; Female ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism ; Biomarkers/metabolism ; Middle Aged ; Retrospective Studies ; Aged ; *Angiogenesis Inhibitors/therapeutic use/administration & dosage ; Photochemotherapy/methods ; Treatment Outcome ; *Choroidal Neovascularization/drug therapy/metabolism ; Visual Acuity ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Choroid/blood supply/pathology ; Ranibizumab/therapeutic use ; Polypoidal Choroidal Vasculopathy ; },
abstract = {While standard anti- vascular endothelial growth factor (VEGF) therapy, with or without photodynamic therapy (PDT), is effective for patients with polypoidal choroidal vasculopathy (PCV), not all achieve optimal visual outcomes. This study aimed to compare fortified (double the dose and the volume of the standard one) anti-VEGF combined with PDT versus fortified anti-VEGF monotherapy and to investigate biomolecular profiles and disease relationships among PCV, neovascular age-related macular degeneration (nvAMD), and central serous chorioretinopathy (CSCR). The goal was to identify novel pathways to inform future therapeutic strategies, including hypoxia-inducible factors (HIF)-1α inhibitors. This retrospective cohort study included 23 eyes with indocyanine green-confirmed type C PCV. One eye treated with transpupillary thermotherapy was not included in the following two groups. Patients received either combined therapy (PDT + fortified-dose anti-VEGF; n = 12) or fortified-dose anti-VEGF monotherapy (n = 10). Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Secondary outcomes included injection burden and recurrence. Exploratory analyses examined aqueous biomarkers, including VEGF, placental growth factor (PlGF), β-catenin, HIF-1α, and Wnt1 across PCV, CSCR, and nvAMD to identify novel therapeutic targets. Significant (p = 0.003/p = 0.005) median CRT reduction was similar (p = 0.468) between groups (combined/monotherapy: 137.5 µm/106.5 µm). BCVA (median [Q1, Q3]) change in logarithm of the minimum angle of resolution (LogMAR) was not statistically significant (p = 0.279), with 0.25 [0.00, 0.98] in the combined group versus 0.00 [-0.03, 0.28] in the monotherapy group. Treatment burden of anti-VEGFs per person per year was lower with combined therapy (1.16 ± 0.47# PDT + 2.81 ± 0.92# anti-VEGF injections) compared with monotherapy (4.61 ± 1.49# injections). Six eyes demonstrated recurrence at a mean of 15.5 months. Incomplete regression of polyps and branching vascular networks was observed in all eyes. Exploratory biomarker analysis revealed significantly (p < 0.05) higher VEGF and PlGF levels in nvAMD compared with PCV. nvAMD also demonstrated significantly (p < 0.05) higher β-catenin and lower HIF-1α levels relative to PCV and CSCR, while no significant biomarker differences were observed between PCV and CSCR. Combined therapy or monotherapy with fortified anti-VEGFs reduced treatment burden and achieved significant anatomical improvement but did not yield superior functional outcomes, highlighting the therapeutic difficulty of type C PCV. Biomarker profiling revealed shared hypoxia-related mechanisms between PCV and CSCR, with elevated HIF-1α compared to nvAMD indicating a "preliminary" possible role for HIF-1α inhibitors. Differential expression of these biomarkers highlights additional molecular pathways that may inform future targeted interventions.},
}

Humans
Male
Female
*Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
Biomarkers/metabolism
Middle Aged
Retrospective Studies
Aged
*Angiogenesis Inhibitors/therapeutic use/administration & dosage
Photochemotherapy/methods
Treatment Outcome
*Choroidal Neovascularization/drug therapy/metabolism
Visual Acuity
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
Choroid/blood supply/pathology
Ranibizumab/therapeutic use
Polypoidal Choroidal Vasculopathy

@article {pmid41681815,
year = {2026},
author = {Gołębiewska, J and Jędrzejewska, IK and Mędrzycka, J and Przybyś, M and Różycki, R},
title = {Non-Exudative Macular Neovascularization in Various Acquired Macular Degenerations with Double- and Triple-Layer Sign on OCT.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/diagnostics16030497},
pmid = {41681815},
issn = {2075-4418},
abstract = {Background/Objectives: To investigate the rate of exudative progression over time in patients with non-exudative macular neovascularization (NE-MNV) associated with various acquired macular degenerations presenting with a double-layer sign (DLS) or triple-layer sign (TLS) on optical coherence tomography (OCT), and to identify potential predictors of this progression. Methods: Fifty-one eyes of fourty-nine patients with a DLS or TLS on OCT images were identified. OCT angiography (OCTA) was performed to detect NE-MNV, and only eyes with confirmed NE-MNV were included in the final analysis. Central macular thickness (CMT), choroidal thickness (CT), morphology of the abnormal vessels, the duration of follow-up, progression to active exudative MNV, and the status of the contralateral eye were assessed. Results: The final analysis included 32 eyes of 30 participants with NE-MNV. The median observation period was 46 months. The causes of NE-MNV were age- related macular degeneration (AMD) in 59.38% of eyes, pachychoroid epitheliopathy (PPE) in 37.50%, and other causes in 3.12%. Exudation developed in 15.62% of eyes (median time to onset: 24 months), predominantly in the AMD subgroup. Abnormalities in the fellow eye were present in 59.38% of cases. Neither age nor other factors, including sex, cause of MNV, CMT, CT, MNV morphology, or fellow eye status, were statistically significant predictors of progression to active MNV (p = 0.67, p > 0.99, p = 0.62, p = 0.09, p = 0.09, p = 0.2, p = 0.62, resp.). Conclusions: NE-MNV is an asymptomatic condition that may occur in the course of various retinal diseases. While DLS and TLS demonstrate high sensitivity and specificity for the diagnosis of NE-MNV, their presence does not always indicate concurrent MNV. Multimodal imaging is essential for accurate monitoring of these patients and detection of potential disease progression.},
}

@article {pmid41681740,
year = {2026},
author = {Ozturk, M and Ağın, A},
title = {Choriocapillaris Flow and Retinal Vascular Fractal Dimension in Dry Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/diagnostics16030422},
pmid = {41681740},
issn = {2075-4418},
abstract = {Background/Objective: To evaluate the association between optical coherence tomography angiography (OCTA)-derived choriocapillaris flow (CCflow), retinal vascular fractal dimension (FD), and drusen burden in eyes with dry age-related macular degeneration (AMD). Methods: This retrospective study included 113 eyes from 73 patients with dry AMD. Eyes were classified into large and small drusen groups based on median drusen area. OCTA-derived CCflow and FD indices of the superficial and deep capillary plexuses were analyzed. Patient-level clustered analyses were performed using linear mixed-effects and generalized estimating equation models to account for inter-eye correlation. Results: Eyes with large drusen showed significantly lower CCflow compared with those with small drusen (p < 0.001), whereas FDsup did not differ between groups, and FDdeep demonstrated only a near-significant trend toward higher values. CCflow was moderately and negatively correlated with drusen area (ρ = -0.452, p < 0.001), whereas FDdeep showed no significant correlation in unadjusted analyses (ρ = 0.137, p = 0.148). In patient-level age-adjusted multivariable models accounting for inter-eye dependency, CCflow remained independently associated with drusen burden, while FDdeep demonstrated an independent association only after adjustment for age. Conclusions: Reduced CCflow is independently associated with increased drusen burden in dry AMD. FD metrics provide complementary descriptive information regarding microvascular remodeling but do not function as independent biomarkers. CCflow may serve as a robust quantitative indicator of early choroidal compromise in dry AMD.},
}

@article {pmid41681737,
year = {2026},
author = {Bepery, C and Rahaman, GMA and Debnath, R and Saha, S and Islam, MS and Abir, MEI and Sarker, SK},
title = {BanglaOCT2025: A Population-Specific Fovea-Centric OCT Dataset with Self-Supervised Volumetric Restoration Using Flip-Flop Swin Transformers.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/diagnostics16030420},
pmid = {41681737},
issn = {2075-4418},
abstract = {Background: Age-related macular degeneration (AMD) is a major cause of vision loss, yet publicly available Optical Coherence Tomography (OCT) datasets lack demographic diversity, particularly from South Asian populations. Existing datasets largely represent Western cohorts, limiting AI generalizability. Moreover, raw OCT volumes contain redundant spatial information and speckle noise, hindering efficient analysis. Methods: We introduce BanglaOCT2025, a retrospective dataset collected from the National Institute of Ophthalmology and Hospital (NIOH), Bangladesh, using Nidek RS-330 Duo 2 and RS-3000 Advance systems. We propose a novel preprocessing pipeline comprising two stages: (1) A constraint-based centroid minimization algorithm automatically localizes the foveal center and extracts a fixed 33-slice macular sub-volume, robust to retinal tilt and acquisition variability; and (2) A self-supervised volumetric denoising module based on a Flip-Flop Swin Transformer (FFSwin) backbone suppresses speckle noise without requiring paired clean reference data. Results: The dataset comprises 1585 OCT volumes (202,880 B-scans), including 857 expert-annotated cases (54 DryAMD, 61 WetAMD, and 742 NonAMD). Denoising quality was evaluated using reference-free volumetric metrics, paired statistical analysis, and blinded clinical review by a retinal specialist, confirming preservation of pathological biomarkers and absence of hallucination. Under a controlled paired evaluation using the same classifier with frozen weights, downstream AMD classification accuracy improved from 69.08% to 99.88%, interpreted as an upper-bound estimate of diagnostic signal recoverability rather than independent generalization. Conclusions: BanglaOCT2025 is the first clinically validated OCT dataset representing the Bengali population and establishes a reproducible fovea-centric volumetric preprocessing and restoration framework for AMD analysis, with future validation across independent and multi-centre test cohorts.},
}

@article {pmid41680791,
year = {2026},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Can MicroRNAs serve as reliable biomarkers and novel therapeutic targets in age-related macular degeneration? A systematic review and meta-analysis.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-025-07593-x},
pmid = {41680791},
issn = {1479-5876},
}

@article {pmid41680690,
year = {2026},
author = {Mesen, S and Yılmaz, MN},
title = {Investigation of pan-immune inflammatory value in patients with age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04674-3},
pmid = {41680690},
issn = {1471-2415},
abstract = {PURPOSE: The purpose of this study was to evaluate the systemic pan-immune inflammatory value (PIV) in wet and dry cases of age-related macular degeneration.

METHODS: Patients diagnosed with AMD between 2020 and 2025 were retrospectively identified. The participants were divided into the wet AMD, dry AMD, and control groups. Their complete blood count (CBC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, and C-reactive protein data were obtained. Neutrophil-to-lymphocyte, monocyte-to-lymphocyte, platelet-to-lymphocyte, and neutrophil-to-HDL ratios were calculated. The PIV was calculated as follows: (neutrophil × platelet × monocyte/lymphocyte count). The central macular and subfoveal choroidal thicknesses were measured manually from the spectral domain optical coherence tomography (OCT) images.

RESULTS: Of the 72 cases included in the study, 25 were wet AMD, 26 were dry AMD, and 21 were controls. According to the statistical analysis, the white blood cell count (7.89 ± 1.82 vs. 6.66 ± 1.75), neutrophil count (5.02 ± 1.42 10[9]/L vs. 4.11 ± 1.35 10[9]/L), monocyte count (0.64 ± 0.16 10[9]/L vs. 0.49 ± 0.18 10[9]/L), and PIV (414.31 ± 268.02 vs. 270.33 ± 161.84) were higher in the wet AMD group than in the dry AMD group. The monocyte count (0.64 ± 0.16 10[9]/L vs. 0.49 ± 0.17 10[9]/L) and PIV (414.31 ± 268.02 vs. 270.13 ± 127.84) were higher in the wet AMD cases than in the control group. No statistically significant difference was found between the dry AMD and control groups.

CONCLUSION: In our study, the PIV was statistically significantly higher in the wet AMD group than in the dry AMD and control groups. Obtaining CBC data is a highly cost-effective and practical method for calculating PIV. PIV calculation can be helpful in the follow-up of patients with AMD, especially those at high risk of converting from dry AMD to wet AMD.},
}

@article {pmid41679663,
year = {2026},
author = {Shu, Q and Lin, Y and Su, W and Peng, H and Wang, X},
title = {Exendin-4 alleviates Aβ1-40-induced apoptosis and calcium dysregulation in RPE cells through the CHP1/NHE1 complex.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {117789},
doi = {10.1016/j.bcp.2026.117789},
pmid = {41679663},
issn = {1873-2968},
abstract = {Age-related macular degeneration (AMD) is a leading cause of visual impairment in elderly individuals and is influenced by various factors, such as age, genetics, and environmental conditions. While research into therapies for dry AMD is rapidly advancing, effective interventions are still lacking, underscoring the urgent need for new drug development. Recent studies have highlighted the multifaceted pharmacological activities of Exendin-4 (EX-4), including its anti-inflammatory, antioxidant, and antiapoptotic properties, along with its role in maintaining calcium homeostasis. The precise effects of EX-4 on AMD and its immediate target remain unclear. In this study, we investigated whether EX-4 could protect against Aβ1-40-induced AMD and explored the underlying mechanism. Our findings indicated that pretreatment with EX-4 alleviated apoptosis and restored calcium homeostasis both in vivo and in vitro. To identify the target of EX-4, we employed proteome microarrays and pulldown LC‒MS/MS analyses. Our results revealed that EX-4 bound to Calcineurin-like EF-hand protein 1(CHP1), reducing CHP1 protein expression in a concentration-dependent manner. This interaction led to a subsequent reduction in apoptosis and the normalization of intracellular Ca[2+] levels through the CHP1/NHE1 complex. Furthermore, we demonstrated that the inhibitory effects of EX-4 on apoptosis and calcium signaling were reversed by knocking down or overexpressing CHP1 in vitro. Finally, in AMD mice with CHP1-deficient retinas, the beneficial effects of EX-4 on apoptosis and calcium signaling were partially attenuated. In summary, our results suggest that the interaction of EX-4 with CHP1 has therapeutic potential for AMD, likely through alleviating apoptosis and restoring calcium homeostasis.},
}

@article {pmid41679584,
year = {2026},
author = {Saeidifard, S and Saltykova, IV and Gerner-Mauro, KN and Schill, AW and Larin, KV and Poché, RA},
title = {Brillouin Microscopic Assessment of Retinal Stiffness During Reactive Müller Gliosis.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110926},
doi = {10.1016/j.exer.2026.110926},
pmid = {41679584},
issn = {1096-0007},
abstract = {Increased retinal stiffness is associated with reactive gliosis, fibrosis, and extracellular matrix remodeling-hallmarks of early retinal damage in conditions such as age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. In this study, we demonstrate that Brillouin microscopy can detect stiffness changes in the damaged mouse retina that coincide with reactive Müller gliosis. Using acute retinal slice cultures, we generated two-dimensional Brillouin maps of both NMDA-damaged and untreated control retinas. Raw spectral images were processed to calculate the Brillouin frequency shift (BFS), which serves as a readout of tissue stiffness. Within 24 hours of NMDA treatment, damaged retinas exhibited a significant increase in BFS relative to controls, indicating a rapid rise in retinal stiffness following neuronal cell death. While this biomechanical change likely reflects multiple cellular and molecular contributions, we show that the Brillouin signal localizes within the radial domain of Müller glia. These findings, along with single-cell mRNA sequencing analysis of damaged retinas, suggest that reactive Müller glia are key contributors to the observed increase in retinal stiffness. Collectively, our results establish Brillouin microscopy as a powerful tool to spatially resolve stiffness changes in the retina during neurodegeneration, provide a rationale for probing the specific mechanisms underlying these biomechanical alterations, and support the further development of Brillouin imaging as an in vivo platform for detecting early retinal pathology.},
}

@article {pmid41677821,
year = {2026},
author = {Christou, EE and Ivanova, T and Patton, N and Moussa, G and Kiraly, P and Huelin, FJ and MacLaren, RE and Jalil, A},
title = {A literature review of macular holes in age-related macular degeneration: insights into the pathogenesis, prognosis and surgical outcomes.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41677821},
issn = {1435-702X},
}

@article {pmid41677389,
year = {2026},
author = {Youssif, AA and Liu, P and Gaczkowski, D and Quaggin, SE and Jin, J and Thomson, BR},
title = {A Highly Active Angiopoietin 1 Mimetic Potentiates Angiogenesis in Mouse Models of Choroidal Neovascularization.},
journal = {Translational vision science & technology},
volume = {15},
number = {2},
pages = {16},
doi = {10.1167/tvst.15.2.16},
pmid = {41677389},
issn = {2164-2591},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/drug therapy/pathology ; *Angiopoietin-1/pharmacology ; Disease Models, Animal ; Mice ; Mice, Inbred C57BL ; Receptor, TIE-2/metabolism ; Recombinant Fusion Proteins/pharmacology ; Angiogenesis ; },
abstract = {PURPOSE: The angiopoietin (ANGPT) pathway, comprised of the ANGPT ligands and their receptor Tie2, mediates angiogenesis and is a compelling target for neovascular age-related macular degeneration (nvAMD). Tie2 phosphorylation by ANGPT1 is associated with vascular stability and may be protective in nvAMD. In contrast, ANGPT2 potentiates angiogenesis and the bispecific ANGPT2/VEGF blocking antibody Faricimab has recently been approved for nvAMD. However, despite clear links between the ANGPT pathway and nvAMD and the success of Faricimab, poor characteristics of existing ANGPT1-based therapies have hindered their adoption as an alternate targeting strategy.

METHODS: Hepta-ANGPT1 is an ANGPT1-mimetic fusion protein with improved activity, solubility, and half-life, addressing limitations of earlier mimetics. Here we used laser-induced and RNV3 (JR5558) models of mouse choroidal neovascularization (CNV) to investigate Hepta-ANGPT1 in CNV and explore its potential as a therapy for nvAMD.

RESULTS: Hepta-ANGPT1 induced robust Tie2 phosphorylation in the choroid and did not lead to angiogenesis in healthy eyes. However, after laser CNV, we observed increased neovascularization in Hepta-ANGPT1-treated eyes, as well as increased number and size of neovascular lesions in treated RNV3 mice, indicating that Hepta-ANGPT1 potentiated angiogenesis. In contrast, CNV lesion size was smaller in Tie2 knockout mice, and no Hepta-ANGPT1-mediated increase was observed in knockout animals, confirming specificity.

CONCLUSIONS: Although previous studies have found ANGPT1 to be protective in mouse CNV, Tie2 activation is pro-angiogenic in other tissues, including the cornea and iridocorneal angle. Hepta-ANGPT1 induced a similar effect in CNV, suggesting that under certain conditions, Tie2 activation can be detrimental in this disease.

TRANSLATIONAL RELEVANCE: Understanding the contexts under which Tie2 activation is beneficial and where it is harmful will be critical to successful development of new Tie2-activating drugs for nvAMD.},
}

Animals
*Choroidal Neovascularization/metabolism/drug therapy/pathology
*Angiopoietin-1/pharmacology
Disease Models, Animal
Mice
Mice, Inbred C57BL
Receptor, TIE-2/metabolism
Recombinant Fusion Proteins/pharmacology
Angiogenesis

@article {pmid41676410,
year = {2025},
author = {Deng, Z and Bu, Y and Hou, T},
title = {Visual impairment and frailty: insights from genetic correlation and Mendelian randomization.},
journal = {Archives of medical science : AMS},
volume = {21},
number = {6},
pages = {2513-2521},
pmid = {41676410},
issn = {1734-1922},
abstract = {INTRODUCTION: Visual impairment (VI) is associated with frailty in observational studies, but whether this relationship is causal remains uncertain. This study aimed to investigate the genetic correlation and causal associations between genetically predicted VI and frailty using Mendelian randomization (MR) and linkage disequilibrium score regression (LDSC).

MATERIAL AND METHODS: Genome-wide association studies provided summary data for VI subtypes (glaucoma, cataracts, diabetic retinopathy, age-related macular degeneration, hypermetropia, myopia) and frailty measures (frailty index (FI) and fried frailty score (FFS)). LDSC was used to estimate genetic correlations, and MR was conducted using inverse-variance weighted (IVW) as the primary method, supplemented by MR-Egger and weighted median. Sensitivity analyses, including radial MR, Cochran's Q test, MR-Egger intercept, and MR-PRESSO, were used to assess pleiotropy and heterogeneity.

RESULTS: Significant genetic correlations were found between VI, cataracts, age-related macular degeneration, and frailty. Suggestive correlations were identified between myopia and FI. MR analysis showed increased FI and FFS risks with other cataracts (FI: p = 0.0324; FFS: p = 0.027) and diabetic retinopathy (FI: p < 0.001; FFS: p = 0.0119). Visual disturbances were associated with increased FI risk (p = 0.0101), while age-related macular degeneration elevated FFS risk (p = 0.0251). Reverse analysis revealed that frailty also increased susceptibility to VI. No causal relationships were found for other eye diseases, and analyses showed no evidence of pleiotropy or heterogeneity.

CONCLUSIONS: This study highlights significant genetic associations and bidirectional causal relationships between VI and frailty. Future research should include multiethnic populations and larger datasets to further explore these mechanisms.},
}

@article {pmid41675859,
year = {2026},
author = {Habib, E and Hajj, F},
title = {Nanocarrier-based CircRNA therapeutics in inherited retinal dystrophies.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {2},
pages = {2104-2105},
pmid = {41675859},
issn = {2049-0801},
abstract = {Inherited retinal dystrophies (IRDs) are a genetically diverse group of progressive blinding disorders with limited curative options. Despite advances in gene therapy, most IRD subtypes remain untreatable due to genetic heterogeneity and delivery challenges. Circular RNAs (circRNAs), a class of stable non-coding RNAs, have emerged as novel modulators of retinal gene expression. Recent developments in nanocarrier technology enable targeted delivery of circRNA mimics and inhibitors to retinal tissues, offering a promising therapeutic alternative. These platforms utilize lipid nanoparticles, polymeric micelles, and exosomes to bypass the blood-retinal barrier and enhance cellular uptake. Preclinical studies demonstrate restoration of photoreceptor survival pathways and delayed retinal degeneration in murine IRD models. Additionally, circRNA nanotherapy has shown efficacy in related retinal conditions such as age-related macular degeneration and diabetic retinopathy. However, translational hurdles, including invasive delivery routes, off-target effects, and regulatory gaps, limit clinical adoption. Nanocarrier-mediated circRNA modulation represents a next-generation strategy for precision therapy in IRDs, with potential to reshape the future of retinal disease management.},
}

@article {pmid41675764,
year = {2026},
author = {Habib, E and Hajj, F},
title = {ROFI: a deep learning-based ophthalmic sign-preserving and reversible patient face anonymizer.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {2},
pages = {2116-2117},
pmid = {41675764},
issn = {2049-0801},
abstract = {Ophthalmic diseases such as diabetic retinopathy, glaucoma, age-related macular degeneration, and inherited retinal dystrophies remain leading causes of visual impairment worldwide, necessitating accurate diagnosis and longitudinal monitoring. Modern ophthalmology increasingly relies on facial and ocular imaging, yet the integration of artificial intelligence (AI) into these workflows raises significant privacy concerns. ROFI (Reversible Ophthalmic Face Image anonymizer) is a novel deep learning-based framework designed to anonymize patient facial features while preserving ophthalmic signs essential for diagnosis. By employing weakly supervised learning and neural identity translation, ROFI achieves high accuracy in retaining ocular disease markers while ensuring reversibility for authorized clinical review. Comparative studies demonstrate that anonymized images maintain diagnostic fidelity for retinal disease classification, while AI-based intraoperative guidance systems further enhance surgical precision and patient safety. Despite these advances, challenges remain regarding dataset diversity, external validation, bias, and cost-effectiveness, particularly in resource-limited settings. Future strategies should emphasize multicenter validation, integration into electronic health records, and awareness campaigns to promote adoption. ROFI represents a significant step toward balancing patient privacy with diagnostic accuracy, offering a scalable solution for secure, AI-driven ophthalmic care.},
}

@article {pmid41675446,
year = {2026},
author = {Yavari, N and Gupta, AS and Mitsios, A and Hung, JH and El-Feky, D and Nguyen, CD and Yasar, C and Anover, FA and Saengsirinavin, AO and Mobasserian, A and Akhavanrezayat, A and Elaraby, O and Zhang, X and Than, NTT and Toth, AB and Agarwal, D and Lin, J and Or, C and Nguyen, QD},
title = {Bilateral hemorrhagic occlusive retinal vasculitis and panuveitis following intravitreal faricimab injection: A clinicopathologic case study.},
journal = {American journal of ophthalmology case reports},
volume = {41},
number = {},
pages = {102532},
pmid = {41675446},
issn = {2451-9936},
abstract = {PURPOSE: To describe the clinicopathological study of severe bilateral intraocular inflammation following intravitreal (IVT) injection of faricimab in a patient with neovascular age-related macular degeneration (nAMD).

OBSERVATION: An 80-year-old Caucasian female with bilateral nAMD presented with blurry vision and ocular pain after receiving bilateral IVT injections of faricimab on separate days from different lots. The patient experienced significant reduction in her visual acuity, from 20/40 to counting-fingers in the right eye and from 20/50 to hand-motion in the left eye; intraocular pressure (IOP) was elevated in both eyes at 48 mmHg and 49 mmHg. Anterior segment examination revealed bilateral diffuse mutton-fat keratic precipitates and fundus examination revealed bilateral vitreous opacities. Fluorescein angiography demonstrated optic disc leakage and bilateral hemorrhagic occlusive vasculitis. Following initial management with systemic corticosteroid, a subsequent unilateral subconjunctival dexamethasone implant, and pars plana vitrectomy, ocular inflammation subsided significantly along with the normalization of IOP. Cytology examination of vitreous samples showed the presence of chronic inflammatory cells in the vitreous.

CONCLUSION: The case highlights the clinical presentation, detailed findings, and successful treatment strategy for hemorrhagic occlusive retinal vasculitis and panuveitis induced by IVT injection of faricimab. Cytopathology analysis of vitreous samples provides novel insights regarding inflammatory mechanisms underlying this rare but potentially sight-threatening complication.},
}

@article {pmid41674807,
year = {2026},
author = {Wu, E and Du, K and Thomas, T and Shin, C and Jiang, J and Navidzadeh, J and Hasan, N and Yao, J and Zhang, M and Sahel, J and Chhablani, J},
title = {Neoplasms Associated with the Onset of Age-Related Macular Degeneration: A Case-Control Study Using the All of Us Cohort.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8396983/v1},
pmid = {41674807},
issn = {2693-5015},
abstract = {Purpose: This study investigated the association between prior diagnoses of neoplasms and the onset of age-related macular degeneration (AMD). Methods: A retrospective case-control study was conducted using health records from 2 724 individuals in the All of Us Program, a longitudinal cohort of U.S. adults. Odds ratios (OR) and Fisher's exact tests were used to evaluate associations between neoplasms and AMD in a matched cohort. Kaplan-Meier survival analysis assessed how neoplasms affected time to AMD onset. Results: Benign neoplasms of the colon (OR: 1.90, 95% CI: 1.55-2.33), skin (OR: 1.46, 95% CI: 1.16-1.84), and rectum (OR: 2.90, 95% CI: 1.53-5.48) showing the strongest and statistically significant associations with AMD. Patients with these benign neoplasms also developed AMD earlier. Although malignant neoplasms of skin of face (OR: 1.97, 95% CI: 1.11-3.49), prostate (OR: 1.47, 95% CI: 0.98-2.22), and breast (OR: 1.39, 95% CI: 0.95-2.02) were also more frequent in AMD patients, these associations were not as significant. Conclusion: Insights into the associations between neoplasms and earlier AMD onset may help ophthalmologists identify at-risk patients and enable earlier intervention. These findings suggest shared pathophysiological mechanisms, such as chronic inflammation and vascular dysfunction, may contribute to both tumour formation and AMD development.},
}

@article {pmid41674610,
year = {2026},
author = {Hoshi, S and Wang, X and Kadomoto, S and Liu, R and Ip, M and Sadda, SR and Sarraf, D and Zhang, Y},
title = {Early Photoreceptor Disruption in Emerging Subretinal Drusenoid Deposits Detected by Adaptive Optics Imaging.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.01.28.26344907},
pmid = {41674610},
abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are a distinct entity in age-related macular degeneration (AMD) and associated with photoreceptor impairment during progression. Their early impact on photoreceptors remains incompletely understood. This study examined photoreceptor reflectivity during the phase when SDDs were not clinically detectable on optical coherence tomography (OCT) using adaptive optics scanning laser ophthalmoscopy (AOSLO).

DESIGN: Longitudinal observational study.

PARTICIPANTS: Patients with intermediate AMD.

METHODS: Six eyes of four patients with intermediate AMD and predominantly SDDs underwent multimodal imaging 3-4 times over 3.5 years. Individual SDDs were graded using an OCT-based 3-stage system at each time point. Cross-sectional retinal structure and photoreceptor reflectivity at the location where the new SDDs developed during follow-up were evaluated using OCT and AOSLO.

MAIN OUTCOME MEASURES: Photoreceptor reflectivity change prior to and during SDD development.

RESULTS: Forty-eight retinal locations where new dot-type SDDs developed during follow-up were identified. AOSLO revealed reduced photoreceptor reflectivity in these regions before OCT demonstrated clinically evident deposits (stage ≥ 1) between the ellipsoid zone and the retinal pigment epithelium at the corresponding sites. The mean time to development of stage 1, stage 2, and stage 3 SDDs was 11.78 ± 5.01, 17.40 ± 6.08, and 18.72 ± 4.08 months, respectively.

CONCLUSIONS: High-resolution adaptive optics confocal imaging enables detection of photoreceptor optical property alterations at a stage when SDDs are not yet evident on OCT. This finding underscores the exceptional sensitivity of photoreceptors to minimal structural or functional perturbations during SDD formation and defines an early window for potential intervention.},
}

@article {pmid41673898,
year = {2026},
author = {Licht, A and Mavris, Y and Latz, C and Schuster, AK and Ponto, KA and Mirshahi, A},
title = {Lost to follow-up while undergoing intravitreal injection therapy: barriers to adherence in a real-world setting.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00808-3},
pmid = {41673898},
issn = {2056-9920},
}

@article {pmid41672305,
year = {2026},
author = {Li, HL and Xu, Y and Mo, JS and Zhao, XY and Zhong, CL and Jia, ZW and Wang, XL and Zhao, BC and Chen, YM and Zheng, KW and Zhang, XL and Wang, QP},
title = {Single intravitreal injection of lipid nanoparticles delivering circular mRNA of nicotinamide phosphoribosyltransferase protects against dry AMD.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {114691},
doi = {10.1016/j.jconrel.2026.114691},
pmid = {41672305},
issn = {1873-4995},
abstract = {Age-related nicotinamide adenine dinucleotide (NAD[+]) deficiency is implicated in numerous pathologies, including dry age-related macular degeneration (AMD). Current NAD[+]-boosting strategies, reliant on precursors like nicotinamide mononucleotide (NMN), necessitate repeated dosing and offer transient effects, limiting therapeutic utility. Here, we address this critical limitation by developing a single-dose therapy using circular mRNA (circ-mRNA) to deliver functional nicotinamide phosphoribosyl transferase (NAMPT), the essential rate-limiting enzyme in NAD[+] salvage. Engineered via permuted intron-exon (PIE) splicing, our circNAMPT exploits the exceptional stability and persistent translation capacity inherent to circular RNA scaffolds. Encapsulation in β-sitosterol-optimized lipid nanoparticles (LNPs) ensures robust intracellular delivery. In vitro, circNAMPT-LNP drives sustained NAMPT expression and prolonged NAD[+] elevation, circumventing precursor limitations. In a stringent sodium iodate-induced dry AMD model, a single intravitreal circNAMPT-LNP injection matched the neuroprotective efficacy of 14 consecutive daily intraperitoneal NMN doses confirmed by histological integrity and functional preservation. This work establishes engineered circ-mRNAs as a transformative platform for durable, single-dose therapeutic protein delivery, demonstrates potential as a disease-modifying therapy for dry AMD. Its applicability extends broadly to systemic disorders driven by NAD[+] deficiency in aging.},
}

@article {pmid41671246,
year = {2026},
author = {Zeng, J and Shang, W and Ren, P and Ke, X and Zhao, Y and Liu, G and Liu, J and Lu, F and Jiang, X},
title = {Expression of aqueous cytokines and their correlation with retinal morphological biomarkers in nAMD patients.},
journal = {PloS one},
volume = {21},
number = {2},
pages = {e0342259},
pmid = {41671246},
issn = {1932-6203},
mesh = {Humans ; Female ; Male ; *Aqueous Humor/metabolism ; *Cytokines/metabolism ; Biomarkers/metabolism ; Aged ; Middle Aged ; *Retina/pathology/metabolism ; Tomography, Optical Coherence ; *Macular Degeneration/metabolism/pathology ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism ; Cataract/metabolism ; },
abstract = {OBJECTIVE: Neovascular age-related macular degeneration (nAMD) is characterized by pathological neovascularization in the macula, leading to irreversible central vision loss. This study aimed to evaluate cytokine profiles in the aqueous humor of nAMD patients and explore correlation between specific cytokines, clinical characteristics, and retinal morphological features.

METHODS: Our protocol was registered on Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2500106190 and approved by the Biomedical Research Ethics Committee of West China Hospital, Sichuan University (ID: 20231375). A total of 94 patients with nAMD and 34 cataract patients as the control group were enrolled. Aqueous humor samples were collected before anti-VEGF treatment or cataract surgery, and analyzed using cytometric bead array (CBA) for cytokines (MCP-1, ICAM-1, VCAM-1, CA-1, β-FGF, PPK/PK, and VEGF). Retinal structural biomarkers were assessed using optical coherence tomography (OCT), with statistical analysis performed to evaluate correlations between cytokine levels and retinal morphology.

RESULTS: Compared to cataract patients, nAMD patients exhibited elevated levels of CA-1, PPK/PK, ICAM-1, VCAM-1, and MCP-1 (P < 0.05). Baseline best-corrected visual acuity (BCVA) was reduced in nAMD patients with intraretinal fluid (IRF) or pigmentation compared to those without (P < 0.05). Visit BCVA also deteriorated in patients with fibrosis (P < 0.05). Additionally, central foveal thickness (CTR) was significantly thinner in patients with PED or SRF (P < 0.05). Visit BCVA demonstrated positive correlations with baseline BCVA (r = 0.689, P < 0.001). In contrast, the presence of fibrosis and elevated MCP-1 concentration was associated with a poorer visual outcome. In correlation analysis, β-FGF exhibited a negative correlation with CA-1, PPK, ICAM-1. VCAM-1 and MCP-1.

CONCLUSION: In this cross-sectional study, the presence of IRF was significantly associated with reduced BCVA in nAMD patients. Baseline BCVA emerged as a critical predictor of visual prognosis in nAMD. Notably, retinal fibrosis development and elevated MCP-1 level linked to worse clinical outcomes, underscoring their potential as therapeutic targets. While recent anti-VEGF injections decreased VEGF levels in aqueous humor of nAMD patients, the impact of these agents on other cytokines remain unclear, suggesting a need for adjunct therapies to address multifaceted pathogenic pathways.},
}

Humans
Female
Male
*Aqueous Humor/metabolism
*Cytokines/metabolism
Biomarkers/metabolism
Aged
Middle Aged
*Retina/pathology/metabolism
Tomography, Optical Coherence
*Macular Degeneration/metabolism/pathology
Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
Cataract/metabolism

@article {pmid41670698,
year = {2026},
author = {Hashiya, N and Maruko, I and Maruko, R and Kakehashi, M and Kawahara, K and Nishihara, S and Iida, T},
title = {Increased intraocular pressure immediately after aflibercept 8 mg intravitreal injection for neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41670698},
issn = {1435-702X},
}

@article {pmid41669765,
year = {2026},
author = {Liu, W and Li, W and Wang, D and Wu, P and Jiang, J and Liu, Z and Chen, X},
title = {Ferroptosis in retinal pigment epithelial cells: Current status and future developments.},
journal = {Indian journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.4103/IJO.IJO_2875_25},
pmid = {41669765},
issn = {1998-3689},
abstract = {Retinal pigment epithelial (RPE) cells play a crucial role in maintaining the normal function of the retina. In recent years, research on ferroptosis-a novel iron-dependent form of cell death-in RPE cells has gradually attracted attention. This article reviews the mechanisms of ferroptosis in RPE cells, including iron metabolism imbalance, lipid peroxidation, and functional impairment of the glutathione-glutathione peroxidase 4 (GSH-GPX4) system. It explores the association between ferroptosis in RPE cells and retinal diseases such as age-related macular degeneration and Stargardt disease. Additionally, it analyzes the future challenges in current research on ferroptosis in RPE cells, such as gaining in-depth understanding of complex regulatory networks and developing precise intervention strategies, so as to provide new insights and directions for the prevention and treatment of retinal diseases.},
}

@article {pmid41669763,
year = {2026},
author = {Venkatesh, R and Biradar, P and Malwe, G and Prabhu, V and Hande, P and Kathare, R and Raj, P and Roy, R and Yadav, NK and Jayadev, C},
title = {Anti-VEGF safety in evolution: A comprehensive review of ocular and systemic considerations.},
journal = {Indian journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.4103/IJO.IJO_3284_25},
pmid = {41669763},
issn = {1998-3689},
abstract = {Intravitreal anti-vascular endothelial growth factor (VEGF) therapy has transformed the management of retinal and choroidal vascular diseases, delivering substantial and sustained visual benefits across neovascular age-related macular degeneration, diabetic macular edema, and retinal vein occlusions. As treatment paradigms have evolved toward chronic, often lifelong therapy with repeated injections, attention has increasingly shifted from short-term procedural safety to a broader evaluation of ocular and systemic adverse events. Among these, intraocular inflammation (IOI) has emerged as the most debated ocular safety signal, ranging from mild, self-limited sterile inflammation to rare but vision-threatening occlusive retinal vasculitis. At the same time, systemic adverse events remain biologically plausible yet uncommon in the general population. This review provides a contemporary, clinically oriented synthesis of anti-VEGF safety, emphasizing that IOI and systemic events are not uniform drug effects but reflect complex interactions among drug-specific properties, delivery factors, disease substrate, patient susceptibility, and immunogenicity. We outline a mechanistic framework distinguishing acute sterile inflammation driven by innate immune activation from delayed vasculitic phenotypes associated with adaptive immune responses and anti-drug antibodies. A structured five-pillar susceptibility model is proposed to contextualize risk modifiers, alongside phenotype-driven management and prevention strategies. Systemic safety considerations are reviewed with attention to agent-specific pharmacokinetics, high-risk patient phenotypes, and cumulative exposure. By integrating mechanistic insights with clinical phenotyping, risk stratification, and preventive strategies, this review aims to support informed, individualized decision-making. A balanced, prevention-focused approach enables clinicians to preserve the transformative benefits of anti-VEGF therapy while maintaining a high standard of long-term ocular and systemic safety.},
}

@article {pmid41667660,
year = {2026},
author = {Sadeghi, E and Gandhi, P and Davis, E and Singh, SR and Ibrahim, MN and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J},
title = {Three-dimensional choroidal vessels assessment in age-related macular degeneration: a follow-up study.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41667660},
issn = {1476-5454},
abstract = {PURPOSE: This study evaluated longitudinal choroidal vascular changes in dry age-related macular degeneration (dAMD) eyes using a three-dimensional (3D) algorithm.

METHODS: Patients underwent swept-source optical coherence tomography during two follow-up visits. Choroidal boundaries and vessels were segmented using the ResUNet model and Phansalkar thresholding. 3D choroidal maps were created and divided into five sectors. Mean choroidal vessel diameter (MChVD), inter-vessel distance (IVD), volumetric choroidal thickness (ChT), and choroidal vascularity index (CVI) were measured in both visits.

RESULTS: This retrospective cohort study included 30 eyes with AMD. The mean age was 72.8 ± 9.55 years. The mean follow-up duration was 11.6 ± 5.02 months. The mean MChVD increased 16.4 µm (6.8%) over time (239.2 ± 19.8 to 255.6 ± 28.2 µm, P = 0.003), particularly in the nasal and temporal sectors (P < 0.05). The mean IVD increased 21.8 µm (10.8%) over time (201.8 ± 29.0 to 223.7 ± 38.2 µm, P = 0.009), which was significant in the nasal, temporal, and superior sectors (P < 0.05). The ChT showed a decreasing trend, though not statistically significant (190.7 ± 58.0 to 183.4 ± 56.8 µm, P = 0.051). The CVI remained stable during follow-up (0.358 ± 0.034 vs. 0.357 ± 0.040, P = 0.933). MChVD positively correlated with the IVD (r = +0.501, P = 0.005). ChT exhibited a negative correlation with IVD (r = -0.426, P = 0.019).

CONCLUSION: Eyes with dry AMD showed increased MChVD and IVD along with decreased ChT, and we hypothesise that these changes may reflect progressive small-vessel atrophy accompanied by compensatory dilation of larger choroidal vessels during follow-up.},
}

@article {pmid41667658,
year = {2026},
author = {Shah, J and Gerendás, L and Serhan, H and Ahmed, H and Festok, M and Mahrous, MA and Kovacs, KD and Kiss, S},
title = {Association between PCSK9 inhibitor use and risk of age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41667658},
issn = {1476-5454},
}

@article {pmid41667492,
year = {2026},
author = {Huang, W and Qin, L and Xu, M and Zheng, H and Gan, Y and Pei, S and Wu, R and Liu, Y and Zhong, J and Ni, G},
title = {Comprehensive 3D Optical Coherence Tomography Dataset for AMD and DME: Facilitating Deep-Learning-Based 3D Segmentation.},
journal = {Scientific data},
volume = {13},
number = {1},
pages = {224},
pmid = {41667492},
issn = {2052-4463},
support = {61905036//National Natural Science Foundation of China (National Science Foundation of China)/ ; 2021T140090, 2019M663465//China Postdoctoral Science Foundation/ ; },
mesh = {*Tomography, Optical Coherence ; *Deep Learning ; *Macular Degeneration/diagnostic imaging ; Humans ; *Imaging, Three-Dimensional ; *Macular Edema/diagnostic imaging ; *Diabetic Retinopathy/diagnostic imaging ; },
abstract = {Age-related macular degeneration (AMD) and diabetic macular edema (DME) are vision-threatening pathologies for which optical coherence tomography (OCT) provides high-resolution three-dimensional imaging, facilitating comprehensive diagnostic evaluation. Three-dimensional (3D) visualization and precise 3D segmentation of lesions enable accurate assessment of morphology, dimensions, and spatial relationships, thereby enhancing clinical analysis and disease management. However, the lack of a 3D dataset for AMD and DME significantly limits the reliability, robustness, and applicability of deep learning-based 3D segmentation techniques in this field. Here, we present an OCT dataset comprising 224 volumetric images, including 122 for AMD and 102 for DME, annotated with pigment epithelial detachment and intraretinal fluid. We propose a novel 3D segmentation network based on the BiFormer Block, which employs Bi-Level Routing Attention to capture local context and long-range dependencies. Experiments demonstrated that the proposed dataset and network will facilitate the exploration and validation of novel 3D segmentation methods for AMD and DME.},
}

*Tomography, Optical Coherence
*Deep Learning
*Macular Degeneration/diagnostic imaging
Humans
*Imaging, Three-Dimensional
*Macular Edema/diagnostic imaging
*Diabetic Retinopathy/diagnostic imaging

@article {pmid41666372,
year = {2026},
author = {Kim, E and Song, SJ},
title = {FOCAL CHOROIDAL EXCAVATIONS IN A SCREENING COHORT: FUNDUS VISIBILITY AND STRUCTURAL REMODELING IN YOUNGER ADULTS.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004796},
pmid = {41666372},
issn = {1539-2864},
abstract = {PURPOSE: To determine how fundus visibility relates to optical coherence tomography (OCT)-derived morphologic and topographic features of focal choroidal excavation (FCE) and to evaluate systemic and ocular associations in a health-screening cohort.

METHODS: We analyzed 19,048 individuals undergoing health examinations with spectral-domain OCT and fundus photography. FCEs were classified as fundus-visible or fundus-invisible. A 1:2 propensity score matching (age/sex) was performed to compare participants with FCE against non-FCE controls. Generalized estimating equations were used to analyze lesion characteristics, systemic comorbidities, and ocular parameters including intraocular pressure (IOP), choroidal thickness, and macular degeneration.

RESULTS: We identified 252 FCE lesions in 192 participants (1.0%). Compared to matched controls, the FCE group showed no significant differences in systemic comorbidities but had significantly lower IOP (P = 0.026), greater choroidal thickness (P < 0.001), and a higher prevalence of macular degeneration (P = 0.002). Among FCEs, fundus-visible lesions had greater median horizontal diameter (681.0 vs 518.0 µm; P < 0.001) and depth (69.5 vs 45.0 µm; P < 0.001), were located closer to the fovea (611.5 vs 1385.0 µm; P < 0.001), and exhibited higher rates of steep slopes (62.5% vs 42.7%; P = 0.002) and outer nuclear layer thickening (61.7% vs 31.5%; P < 0.001) compared to fundus-invisible lesions.

CONCLUSION: FCE is associated with distinct ocular profiles, including lower IOP and increased choroidal thickness, independent of systemic risk factors. Fundus visibility indicates larger, deeper, and paramacular lesions with specific structural alterations, underscoring the need to recognize subtle fundoscopic irregularities for early OCT detection.},
}

@article {pmid41665215,
year = {2026},
author = {Argun, M and Nazıroğlu, M},
title = {Selenium Nanoparticles Protect Retinal Pigment Epithelial Cells Against Experimental Age-Related Macular Degeneration-Induced Mitochondrial Oxidative Toxicity and Apoptosis Through the Modulation of the TRPM2 Channel.},
journal = {Journal of biochemical and molecular toxicology},
volume = {40},
number = {2},
pages = {e70738},
doi = {10.1002/jbt.70738},
pmid = {41665215},
issn = {1099-0461},
support = {//BSN Health, Analyses, Innovation, Consultancy, Organization, Agriculture, Industry LTD, Isparta, Türkiye/ ; },
mesh = {*TRPM Cation Channels/metabolism ; Humans ; *Macular Degeneration/metabolism/pathology/prevention & control/drug therapy ; *Apoptosis/drug effects ; *Selenium/pharmacology/chemistry ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; *Mitochondria/metabolism/pathology/drug effects ; *Oxidative Stress/drug effects ; Cell Line ; *Nanoparticles/chemistry ; },
abstract = {Excessive Ca[2+] influx leads to mitochondrial oxidative injury and cell death, contributing to the development of age-related macular degeneration (AMD). The protective role of selenium nanoparticle (SeNPs), through inhibition of ADP-ribose- and hydrogen peroxide (H2O2)-induced TRPM2 cation channel stimulation, was recently reported in human retinal pigment epithelial 19 (ARPE-19) cells for hypoxia-induced oxidative cytotoxicity and cell death, but not for AMD. We aimed to investigate the protective effects of SeNPs through inhibition of TRPM2 on AMD (sodium iodate [NaI])-induced oxidative injury, cell death, and apoptosis in ARPE-19 cells. The ARPE-19 cells were divided into four main groups: control (CNT), SeNPs (2.5 μg/mL for 24 h), AMD (10 mM NaI for 24 h) and AMD + SeNPs. The AMD treatment increased TRPM2 current density and cytosolic Ca[2+] and Zn[2+] fluorescence intensities, as well as the percentage of cell death. It also elevated apoptotic markers (caspases 3, 8, and 9) and oxidative stress markers (mitochondrial membrane dysfunction, oxygen free radicals, and lipid peroxidation), while decreasing antioxidants (glutathione and glutathione peroxidase), cell viability and the number of live cells. TRPM2 stimulation further increased these markers. When SeNPs and TRPM2 antagonists were used to treat the AMD-induced increase in TRPM2 activation, they increased antioxidants and cell viability while decreasing oxidative stress and cell death markers. In conclusion, SeNP treatment reduced AMD-induced mitochondrial oxidative cytotoxicity and cell death by inhibiting TRPM2-mediated Ca[2+] signaling. SeNP represents a potential therapeutic option for AMD-induced retinal disorders linked to abnormal oxygen free radical production and Ca[2+] influx.},
}

*TRPM Cation Channels/metabolism
Humans
*Macular Degeneration/metabolism/pathology/prevention & control/drug therapy
*Apoptosis/drug effects
*Selenium/pharmacology/chemistry
*Retinal Pigment Epithelium/metabolism/pathology/drug effects
*Mitochondria/metabolism/pathology/drug effects
*Oxidative Stress/drug effects
Cell Line
*Nanoparticles/chemistry

@article {pmid41665064,
year = {2026},
author = {Tunon-Robinson, I and Zhang, R and Nguyen, AK},
title = {Visual Acuity Outcomes Following Intravitreal Biological Drug-Induced Retinal Vasculitis: An Intelligent Research in Sight Registry Retrospective Exploratory Analysis.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683251412321},
doi = {10.1177/10807683251412321},
pmid = {41665064},
issn = {1557-7732},
abstract = {PURPOSE: This retrospective exploratory study examines the visual acuity outcomes following a retinal vasculitis (RV) event possibly associated with intravitreal (IVT) biological drugs using a large ophthalmic registry, to gain a better understanding of RV's impact on vision in real-world clinical settings.

METHODS: An ophthalmic registry was used in a retrospective exploratory analysis and focused on subjects who received IVT anti-VEGF and anticomplement therapies. We excluded eyes with RV in the visual acuity analysis that had received more than one IVT biological drug within 2 months before the diagnosis of RV to increase confidence that a single biological drug was possibly associated with the RV event.

RESULTS: A total of 1,998,399 subjects received IVT injections of biological drugs, and 2,115 subjects were diagnosed with RV in at least 1 eye. A total of 436 subjects (531 eyes total) were coded as having RV. There was a 78% increase in eyes that became legally blind (≤20/200 Snellen equivalent) and 46% increase in eyes reading 0 letters (≤count fingers vision) following the RV event.

CONCLUSIONS: In the real world, the number of legally blind eyes substantially increased following the RV diagnosis. Given the retrospective and exploratory nature of this study, all interpretations should be made cautiously, including any suggested association between biological therapy and the occurrence of RV, and prospective studies are necessary to confirm these associations. Further research is indicated to improve the safety of biological therapies for retinal diseases and minimize the risk of serious complications such as RV.},
}

@article {pmid41664540,
year = {2026},
author = {da Silva, CN and Inoue, TT and França Dias, M and Fialho, SL and Silva-Cunha, A},
title = {Intravitreal implants for drug delivery: clinical efficacy, safety, and translational perspectives.},
journal = {Expert opinion on drug delivery},
volume = {},
number = {},
pages = {},
doi = {10.1080/17425247.2026.2629545},
pmid = {41664540},
issn = {1744-7593},
abstract = {INTRODUCTION: Chronic retinal disorders such as age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and noninfectious uveitis are among the leading causes of irreversible visual loss worldwide. Their management depends on repeated intravitreal injections of anti-VEGF agents or corticosteroids, which, despite proven efficacy, are associated with high treatment burden and cumulative risks. Sustained-release intravitreal drug delivery systems (DDSs) are effective strategies to prolong therapeutic activity, enhance bioavailability, minimize adverse events, and improve patient adherence.

AREAS COVERED: This review provides an overview of the evolution, clinical efficacy, and translational potential of intravitreal DDSs, from nonbiodegradable implants to biodegradable systems. Advances in polymeric design, hydrogels, in situ forming systems, and 3D-printed architecture, are discussed alongside emerging clinical candidates. Key formulation, preclinical, and regulatory barriers to clinical translation are also examined. Comprehensive search on PubMed, Scopus, Web of Science, ClinicalTrials.gov, and regulatory repositories was performed (data published up to December 2025).

EXPERT OPINION: Intravitreal DDSs are redefining ocular pharmacotherapy by offering prolonged, localized drug release. However, further innovation in polymer design, bioerodible materials, and sterilization methods is essential to balance safety, efficacy, and manufacturability. Integration of precision medicine and next-generation biomaterials will be key to achieving fully optimized, minimally invasive retinal therapies.},
}