@article {pmid42466416,
year = {2026},
author = {Rivolta, C and Kaminska, K and Moye, A and Quinodoz, M and Zehr, E and Aiteur, A and Calzetti, G and Barberán-Martínez, P and Kühlewein, L and Bodenbender, JP and Ehrenberg, M and Khandhadia, S and Zur, D and Soudry, S and Barili, V and Ambrosini, E and Ottonelli, G and Feliciano-Sánchez, A and Müller, I and Wallerich, S and Galliker, P and Moulin, A and Zuleger, T and Haack, T and Wissinger, B and Stingl, K and García-García, G and Menghini, M and Vincent, A and Heon, E and Mahroo, O and Lotery, A and Webster, A and Arno, G and Millan, J and Ben-Yosef, T and Michaelides, M and Lin, S and Kohl, S and Roll-Mecak, A and Tran, V},
title = {Missense variants in KATNA1 alter microtubule dynamics and underlie dominant macular dystrophy.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-8880283/v1},
pmid = {42466416},
issn = {2693-5015},
abstract = {Inherited retinal diseases (IRDs) encompass a broad spectrum of genetic conditions leading to visual impairment. In this study, we identify KATNA1, encoding the catalytic p60 subunit of the microtubule-severing enzyme katanin, as a previously unrecognized cause of autosomal dominant macular dystrophy (adMD), a form of IRD. Specifically, we could ascertain the presence of 10 heterozygous missense changes affecting six conserved amino acids in 21 individuals from 16 unrelated families from various parts of the world, all presenting with non-syndromic MD of variable severity. Structure-guided analyses indicated that the identified variants potentially disrupt katanin's assembly into hexamers or its ability to bind or hydrolyze ATP, thus compromising its microtubule-severing function. Characterization of patient-derived fibroblasts revealed accumulation of acetylated microtubules both in the cytoplasm and within the primary cilium, together with an altered subcellular distribution of KATNA1. Immunostaining of human retinal tissue showed that KATNA1 specifically localizes to photoreceptors, with distinct distribution patterns between rod and cone photoreceptors. Immunogold transmission electron microscopy confirmed this finding, revealing KATNA1 distribution along the rod axoneme and predominantly within the cone connecting cilium. Together, these results establish KATNA1 as a novel gene associated with adMD, possibly accounting for ~4% of all unresolved MD cases, and associate defective microtubule severing and cytoskeletal dysregulation with macular degeneration.},
}

@article {pmid42457102,
year = {2026},
author = {Zerti, D and Donato, L and Chust, IB and Carozza, G and Giangiulio, O and Stefanini, M and Faella, E and Feligioni, M and Di Gregorio, J and Flati, V and Carl, M and Poggi, L and D'Angelo, R and Passacantando, M and Maccarone, R},
title = {Mitochondrial preservation underlies the antioxidant activity of nanoceria particles in light-induced retinal degeneration.},
journal = {Nanomedicine : nanotechnology, biology, and medicine},
volume = {},
number = {},
pages = {102995},
doi = {10.1016/j.nano.2026.102995},
pmid = {42457102},
issn = {1549-9642},
abstract = {Age-related Macular Degeneration (AMD), the leading cause of blindness worldwide, is a multifactorial disease with mitochondrial dysfunction recognized as an early pathogenic event. In our preclinical studies, we demonstrated that a single Cerium-Oxide Nanoparticles (CeO2-NPs) intravitreal injection in a light-induced degeneration model, was able to counteract the retinal degeneration. Our aim was to investigate whether neuroprotection activity could be correlated with mitochondrial morpho-functional preservation. Bulk transcriptomic profiling of whole retinal tissue revealed that light-induced retinal injury was associated with suppression of mitochondrial-related gene networks, including components of the electron transport chain and regulators of mitochondrial dynamics, whereas CeO2-NPs treatment restored the expression of antioxidant and mitochondrial biogenesis-related genes. Ultrastructural analysis by electron microscopy showed preservation of Retinal Pigmented Epithelial mitochondria's morphology and by high-resolution crystallographic analysis confirmed the intracellular localization of CeO2-NPs in proximity to mitochondria. Furthermore, Western blot analysis demonstrated that CeO2-NPs maintained mitophagy markers at basal levels, preventing excessive activation of mitochondrial quality-control pathways. Together, these findings support mitochondrial preservation as a key mechanism underlying nanoceria-mediated retinal neuroprotection and highlight CeO2-NPs as promising candidates for maintaining retinal homeostasis in AMD.},
}

@article {pmid42457199,
year = {2026},
author = {Barrett, P and Carey, C and O'Riordan, S and Wu, AD and Wallace, E and Biba, M and Kublickiene, K and McCarthy, F and Khashan, A},
title = {Hypertensive Disorders of Pregnancy and the Long-Term Risk of Maternal Retinal and Ophthalmic Disease: A Systematic Review and Meta-Analysis.},
journal = {BJOG : an international journal of obstetrics and gynaecology},
volume = {},
number = {},
pages = {},
doi = {10.1111/1471-0528.70307},
pmid = {42457199},
issn = {1471-0528},
support = {CSF-2023-006/HRBI_/Health Research Board/Ireland ; },
abstract = {BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk of maternal cardio-metabolic disease, but links with future retinal diseases remain unclear.

OBJECTIVE: The objective of this study is to synthesise the published literature on HDP and subsequent retinal and other ophthalmic disease.

SEARCH STRATEGY: Databases including PubMed, Embase, Web of Science, and Cochrane Library were searched to March 2026 following a pre-registered PROSPERO protocol, CRD42024589508.

SELECTION CRITERIA: These included: a population of parous women, exposure to HDP at least once, at least one primary outcome (retinal disease) or secondary outcome (other ophthalmic disease). Women with pre-pregnancy retinal/ophthalmic diseases were excluded.

DATA COLLECTION AND ANALYSIS: Two reviewers independently screened studies, extracted data, and assessed bias using an adapted Newcastle-Ottawa tool. Random-effects meta-analyses were performed.

RESULTS: Of 5673 studies retrieved, 13 were eligible for inclusion (2 450 072 participants). HDP was associated with increased risk of diabetic retinopathy (aRR 3.54, 95% CI 2.19-5.74), particularly after preeclampsia (aRR 4.24, 95% CI 3.51-5.12). HDP-exposed women were also at higher risk of non-diabetic retinopathy (aRR 3.65, 95% CI 1.18-11.33), retinal detachment (aRR 1.54, 95% CI 1.28-1.86), and retinal vascular occlusion (aRR 2.09, 95% CI 1.55-2.81). HDP-exposed women may also be at risk of hypertensive retinopathy and central serous chorioretinopathy, but aRRs did not reach statistical significance. Across individual studies, HDP-exposed women were reported to be at increased risk of cataract extraction, non-infectious uveitis, and choroidal neovascular age-related macular degeneration.

CONCLUSION: Women who experience HDP may be at future risk of retinal and other ophthalmic diseases, particularly diabetic retinopathy. Further observational research is required to confirm these associations.},
}

@article {pmid42458644,
year = {2026},
author = {Matsuyama, A and Miki, A and Oka, T and Ikeuchi, E and Kishimoto-Kishi, M and Miki, K and Imai, H and Nakamura, M},
title = {Real-world functional and anatomical outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration: a phenotype-based analysis by pachychoroid and polypoidal lesion status.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00901-7},
pmid = {42458644},
issn = {2056-9920},
abstract = {BACKGROUND: To evaluate the short-term functional and anatomical outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration (nAMD), and to explore whether the early treatment response varied according to pachychoroid and polypoidal lesion status.

METHODS: This retrospective, multicenter observational study evaluated 45 treatment-naïve eyes of 45 patients with nAMD who received three monthly loading injections of aflibercept 8 mg. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), central choroidal thickness (CCT), and exudative findings (subretinal fluid [SRF], intraretinal fluid [IRF], and subretinal hyperreflective material [SHRM]) were assessed at baseline and at 1, 2, and 4 months. Pachychoroid and polypoidal lesion status was determined using multimodal imaging. Longitudinal changes were analyzed using linear mixed-effects models, with subgroup analyses by pachychoroid and polypoidal lesion status.

RESULTS: At 4 months, mean BCVA improved from 0.27 ± 0.33 to 0.20 ± 0.31 logMAR (P = 0.005), CRT decreased from 382.1 ± 189.7 to 231.3 ± 109.1 μm, and CCT from 263.0 ± 146.5 to 231.0 ± 127.2 μm (both P < 0.001). The dry macula rate (absence of both SRF and IRF) increased from 17.8% to 75.6% (P < 0.001). Functional and retinal anatomical responses were broadly consistent across phenotypes, with no significant time-by-phenotype interactions for BCVA or CRT. Pachychoroid eyes showed a greater CCT reduction (interaction P < 0.001), but this was no longer significant after adjusting for baseline CCT. As exploratory observations, the time-by-polypoidal-lesion interaction for BCVA was not significant (P = 0.052), and residual SHRM at 4 months was present in 0% of polypoidal-lesion eyes versus 22.2% of those without (P = 0.067).

CONCLUSIONS: Intravitreal aflibercept 8 mg led to significant short-term improvements in BCVA, CRT, CCT, and exudative findings in treatment-naïve nAMD, with benefit observed irrespective of pachychoroid or polypoidal lesion status.},
}

@article {pmid42459964,
year = {2026},
author = {Rothaus, K and Grün, M and Faatz, H and Ziegler, M and Spital, G and Lommatzsch, A and Gutfleisch, M and Heimes-Bussmann, B and Lange, C},
title = {Real-world evaluation of an OCT-based AI decision-support system for neovascular AMD activity triage in teleophthalmology.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1870572},
pmid = {42459964},
issn = {2674-0826},
abstract = {PURPOSE: To evaluate real-world agreement between a CE-marked OCT-based AI decision-support system and routine retreatment decisions for neovascular AMD within a teleophthalmology workflow.

METHODS: Retrospective clinical study including 429 OCT examinations from 247 patients (306 treated eyes) with neovascular AMD. Retinal specialists made routine retreatment decisions ("inject" vs "watch-and-wait") using full clinical context. Independently, the AI system (deepeye[®] TPS, version 1.2) analyzed the current OCT volume only (no prior OCT, visual acuity, treatment interval, or clinical notes) and generated a Disease Activity Score (DAS; 0-100) used to derive an "inject" vs "watch-and-wait" recommendation. Discrepant cases were re-evaluated by senior graders to establish a double-senior-graded (DSG) reference standard. Implementation analyses assessed a deferral ("safety zone") strategy. Main outcome measures included agreement/accuracy, sensitivity, and specificity versus real-world decisions and the double-senior-graded (DSG) reference standard, as well as decision coverage under deferral.

RESULTS: Agreement between real-world decisions and AI recommendations was 83.2% (sensitivity 74.7%, specificity 88.0%). Against the double-senior-graded reference standard (DSG), accuracy in the full analysis set (FAS), analyzed at the examination level, was 85.5% (sensitivity 77.2%, specificity 90.4%). Using an empirically optimized DAS threshold, accuracy increased to 88.6% (sensitivity 78.5%, specificity 94.9%) in the eligible retreatment-decision set (ERDS). Application of a deferral policy ("safety zone", DAS 33-64) resulted in automated recommendations for 78.4% of eligible examinations, while 21.6% were deferred due to intermediate DAS values; among examinations with an automated recommendation, accuracy was 92.3% (sensitivity 83.2%, specificity 97.5%). Most misclassifications involved subtle IRF/SRF and SHRM as identified by the reading center and tended to be underestimated by the AI.

CONCLUSION: The evaluated OCT-only AI decision-support output showed substantial agreement with routine retinal-specialist retreatment decisions in a real-world teleophthalmology workflow, particularly when intermediate Disease Activity Scores were deferred to human review. However, false-negative cases and context-dependent discrepancies highlight that the system should support, not replace, clinician judgement. Prospective multicenter validation using longitudinal and multimodal input data is required before broader workflow integration can be recommended.},
}

@article {pmid42460002,
year = {2026},
author = {Choo, DM and Durham, TA and Patel, KG},
title = {Assessing retina-specific ophthalmic counseling generated by an early public large language model across different levels of clinical urgency.},
journal = {Frontiers in digital health},
volume = {8},
number = {},
pages = {1849883},
pmid = {42460002},
issn = {2673-253X},
abstract = {PURPOSE: To evaluate how the quality of retina-specific ophthalmology counseling provided by an early publicly available large language model (LLM) differs when advising patients with varying clinical characteristics and risk factors.

DESIGN: Prospective, cross-sectional study.

SUBJECTS: 18 ophthalmologists.

METHODS: Six patient vignettes were constructed with high- and low-urgency clinical scenarios for diabetic retinopathy (DR), retinal detachment (RD), and age-related macular degeneration (AMD). Based on these vignettes, an LLM (ChatGPT-3.5) was asked to provide written medical counseling in February 2024. Each response was rated on several metrics via 5-point Likert scale by 18 independent reviewers. Notably, readability was assessed both qualitatively via survey and quantitatively via Readable (an online readability tool that incorporates 5 different metrics).

MAIN OUTCOME MEASURES: Counseling generated by the LLM was graded on accuracy, appropriate communication of urgency and empathy, readability, and potential for clinically significant harm.

RESULTS: Counseling accuracy differed across levels of clinical urgency (p = 0.002) but remained consistent between high- and low-urgency vignettes of AMD (p = 0.081) and DR (p = 0.5), albeit not for RD (P < 0.001). Counseling urgency did not differ significantly from clinical urgency of all vignettes, except for the high-urgency AMD (p = 0.013) and high-urgency RD (p < 0.001). While counseling urgency did not significantly differ between high- and low-urgency vignettes of AMD (p = 0.055) and RD (p = 0.3), it did differ for the DR vignettes (p < 0.001). Counseling empathy did not differ across clinical urgency (p = 0.2). Four readability indices (e.g., Flesch Kincaid Grade Level) consistently indicated that college graduation would be required to understand every counseling output. Across all vignettes, the most common reasons for potential difficulty in understanding the counseling were having too much medical (49%) and non-medical (45%) terminology.

CONCLUSIONS: The evaluated LLM-generated counseling outputs were largely similar across the sampled retinal vignettes with differing clinical urgency. Future studies should investigate the optimization of LLM prompting needed to garner counseling of consistent/appropriate accuracy, readability, empathy, and communication of urgency for specific conditions.},
}

@article {pmid42460402,
year = {2026},
author = {Fossataro, C and Savastano, MC and Cusato, M and Cestrone, V and Mottola, F and Hu, L and Campaniello, G and Oreste, G and Giannuzzi, F and Maiola, E and Mastropietro, G and Savastano, A and Valentini, CG and Pellegrino, C and Teofili, L and Rizzo, S},
title = {Transitory vitreous opacities after CB-PRP intravitreal injections in dry AMD patients.},
journal = {Therapeutic advances in ophthalmology},
volume = {18},
number = {},
pages = {25158414261462410},
pmid = {42460402},
issn = {2515-8414},
abstract = {BACKGROUND: Dry age-related macular degeneration currently lacks effective treatments for geographic atrophy. Cord blood platelet-rich (CB-PRP) plasma intravitreal injections are a novel therapy under investigation with promising ad interim results.

OBJECTIVES: To describe the safety profile of cord blood platelet-rich plasma intravitreal injections (IVIs) in dry age-related macular degeneration (AMD) patients.

DESIGN: This prospective, randomized, sham-controlled, open-label experimental trial evaluated the safety of repeated intravitreal CB-PRP injections.

METHODS: The study, conducted from January 2023 to January 2025, investigated the safety and efficacy of CB-PRP IVIs to slow down the progression of geographic atrophy (GA). One eye of each patient was randomly assigned to the monthly, every other month, or every 3 months arm and received 0.05 mL CB-PRP, while the other eye underwent only a sham injection. Complete ophthalmological evaluations were performed at baseline, 3-, 6-, 12-, 18-, and 24-month follow-ups. In addition, slit-lamp and fundus examinations were performed the day after the injection to exclude any adverse effect.

RESULTS: In a total of 328 intravitreal injections, vitreous opacities were observed in the absence of other signs of infection or inflammation only in three cases. All of them showed progressive improvement without treatment, and complete recovery was observed within 2 weeks.

CONCLUSION: Although the pathogenesis of the detected vitreous thickening was not completely clear, the most likely hypothesis was the coexistence of a slightly lower temperature of the CB-PRP sample and individual factors. This mild adverse event occurred only once in each patient involved, with no recurrence during subsequent intravitreal injections. The occurrence of this self-limiting finding after CB-PRP IVIs has not invalidated the safety profile of the procedure.},
}

@article {pmid42460478,
year = {2026},
author = {Yuan, F and Tu, J and Liu, X and Wang, L and Zhou, W and Jin, Y},
title = {Serum NLR, PLR and MNV characteristics as predictors of anti-VEGF plus glucocorticoid efficacy in nAMD.},
journal = {Biomarkers in medicine},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/17520363.2026.2704571},
pmid = {42460478},
issn = {1752-0371},
abstract = {AIM: To evaluate the combined predictive value of serum neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and macular neovascularization (MNV) characteristics for treatment efficacy in neovascular age-related macular degeneration (nAMD) patients receiving anti-VEGF plus glucocorticoid therapy.

PATIENTS AND METHODS: This retrospective study included 145 patients (153 eyes) with nAMD receiving conbercept combined with dexamethasone implant. Patients were categorized as Inactive (n = 89) or Active (n = 64) based on post-treatment MNV activity. Baseline NLR, PLR, and MNV morphology were assessed. Multivariate logistic regression identified independent predictors, and ROC analyses evaluated predictive value.

RESULTS: Patients with persistent MNV activity showed significantly higher baseline NLR, PLR, MNV area, and fractal dimension (all p < 0.001). Multivariate analysis identified baseline visual acuity, MNV type, fluid volumes, MNV morphological parameters, and inflammatory markers as independent predictors. The combined model incorporating inflammatory markers and MNV characteristics demonstrated superior performance (AUC = 0.92, 95% CI: 0.87-0.96) with 79.69% sensitivity and 91.01% specificity.

CONCLUSION: Combining serum inflammatory markers with MNV morphological characteristics enhanced predictive value for treatment response in nAMD patients receiving combination therapy. This integrated approach may facilitate personalized treatment strategies in nAMD management.},
}

@article {pmid42464986,
year = {2026},
author = {Betancourt Sanchez, A and Huynh, A and Blanchard, L and De Groot, A and Klopp, C and Loubière, K and Andriantsiferana, C and Lajoie, B},
title = {Zeaxanthin-Producing Winogradskyella schleiferi Strains.},
journal = {Journal of basic microbiology},
volume = {66},
number = {7},
pages = {e70187},
doi = {10.1002/jobm.70187},
pmid = {42464986},
issn = {1521-4028},
mesh = {*Zeaxanthins/biosynthesis ; Phylogeny ; Mediterranean Sea ; Seawater/microbiology ; RNA, Ribosomal, 16S/genetics ; Temperature ; Carotenoids ; },
abstract = {Two pigmented bacteria strains were isolated from the Mediterranean Sea. Phylogenetic analysis revealed that both strains are affiliated with Winograsdskyella schleiferi Z215. However, in contrast to this reference strain, they can assimilate additional carbon sources such as d-mannose, l-arabinose, d-mannitol, and citrate. Zeaxanthin was identified as the major carotenoid produced by both strains, predominantly in the all-trans configuration. Carotenoid biosynthesis kinetics revealed that pigment production commenced at the early stages of growth, with maximal yields reached between 48 and 56 h (between 1 and 1.3 mg L[-1]). Specific production yields were 0.7 and 0.9 mg g[-1] for the two strains, respectively. Total carotenoid production was influenced by incubation temperature in both strains. Overall, these findings expand the scientific knowledge on carotenoid-producing marine bacteria and highlight the potential of these newly isolated strains as promising candidates for zeaxanthin biotechnological production for a wide range of novel applications ranging from feed additives to treatments for macular degeneration and melanoma.},
}

*Zeaxanthins/biosynthesis
Phylogeny
Mediterranean Sea
Seawater/microbiology
RNA, Ribosomal, 16S/genetics
Temperature
Carotenoids

@article {pmid42465049,
year = {2026},
author = {Bozal, S and Yue, JS and DiStasio, M and Rothrock, A and Zhang, X and Sutova, HE and Bhatta, S and Deschenes, E and Ju, G and Saltzman, WM and Hafler, BP},
title = {Erratum: 415 Designing nanoparticle therapies for age-related macular degeneration - ERRATUM.},
journal = {Journal of clinical and translational science},
volume = {10},
number = {1},
pages = {e105},
pmid = {42465049},
issn = {2059-8661},
abstract = {[This corrects the article DOI: 10.1017/cts.2026.10567.].},
}

@article {pmid42465550,
year = {2026},
author = {Fila, M and Krekora, J and Drożdż, J and Kaarniranta, K and Blasiak, J},
title = {Retinal connections to migraine.},
journal = {Frontiers in neurology},
volume = {17},
number = {},
pages = {1835914},
pmid = {42465550},
issn = {1664-2295},
abstract = {OBJECTIVE: This narrative review aims to examine potential associations between migraine and retinal disorders, with particular attention to retinal migraine, age-related macular degeneration (AMD), retinal vascular occlusions, and photophobia.

BACKGROUND: The role of retinal pathways in migraine pathophysiology remains poorly understood. As a component of the central nervous system, the retina provides a unique and accessible window into neuronal structure and function. Emerging observations suggest that structural and functional retinal changes may occur in individuals with migraine; however, their relevance and consistency across studies remain uncertain.

RESULTS: Visual phenomena are characteristic of migraine aura, yet the extent to which migraine affects retinal structure and function is still unclear. Retinal migraine, while suggestive of a direct retinal involvement, is rare and insufficiently characterized to support mechanistic conclusions. Epidemiological data indicate that individuals with migraine may have an increased risk of neovascular AMD, raising the possibility of shared pathogenic pathways. In addition, photophobia, retinal artery occlusion, and alterations in retinal nerve fiber layer thickness have been reported more frequently in migraine patients than in controls, although causality has not been established. Mechanisms implicated in AMD, including microvascular dysfunction, impaired DNA damage response, disrupted autophagy, and mitochondrial dysregulation, have also been proposed in migraine, but evidence remains limited.

CONCLUSION: Migraine has been linked to several retinal conditions, with AMD showing the most consistent association. While overlapping biological processes are suggested, further studies are needed to clarify their significance and determine whether retinal alterations contribute to migraine pathophysiology or represent secondary phenomena.},
}

@article {pmid42450389,
year = {2026},
author = {Predescu, NC and Papuc, C and Stefan, G and Rosu, PM and Chervenkov, M and Saracila, M and Panaite, TD and Ionascu, I},
title = {Anthocyanins as Adjunctive Dietary Modulators of the Gut-Eye Axis: Bioavailability, Biotransformation, and Implications for Ocular Health.},
journal = {Foods (Basel, Switzerland)},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/foods15132270},
pmid = {42450389},
issn = {2304-8158},
abstract = {Retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR) are major causes of visual impairment and are closely associated with oxidative stress, inflammation, vascular dysfunction, and metabolic imbalance. Increasing evidence suggests that gut microbiota also contributes to retinal homeostasis, supporting the emerging concept of the gut-eye axis. In this context, dietary anthocyanins-with blueberry anthocyanins serving as a primary representative model-have attracted attention as potential adjunctive nutritional modulators of ocular health. However, their biological effects are strongly influenced by their limited bioavailability and extensive gastrointestinal metabolism. The objective of this review is to analyze the gastrointestinal fate of dietary anthocyanins and to discuss how their absorption, enzymatic transformation, and microbial biotransformation may influence ocular protection through the gut-eye axis. The review summarizes current knowledge regarding anthocyanin stability in the oral cavity, stomach, small intestine, and colon, as well as the formation of circulating phenolic metabolites generated by the host and through microbial metabolism. In addition, the molecular mechanisms through which anthocyanins and their metabolites may support retinal health are examined, including antioxidant, anti-inflammatory, vasoprotective, and neuroprotective actions. Overall, dietary anthocyanins, illustrated through the rich profile of blueberries, represent promising adjunctive compounds for supporting ocular health, although further clinical and mechanistic studies are still required.},
}

@article {pmid42452359,
year = {2026},
author = {Sandali, O and Tahiri Joutei Hassani, R and Audo, I and Gualino, V and Tchikladze Merand, C and Borderie, V},
title = {Effect of Minimizing Light Exposure with Digital Visualization on Macular Function After Cataract Surgery in Patients with AMD: A Randomized Controlled Trial.},
journal = {Journal of clinical medicine},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/jcm15134897},
pmid = {42452359},
issn = {2077-0383},
support = {IIT#73473171//Alcon (United States)/ ; },
abstract = {Purpose: To assess whether reducing intraoperative light exposure preserves macular function after cataract surgery in patients with AMD. Methods: A total of 42 eyes of 42 patients with AMD were randomized in a prospective study. The primary outcome was the change in photopic (ERG) b-wave amplitude at one hour after surgery (V2). Secondary outcomes included ERG implicit time, multifocal ERG, visual acuity, and macular thickness, assessed at V2, V3 (day 1), and V4 (1 month). Results: Mean intraoperative light exposure was significantly lower in the 3D group than in the standard group (3938 vs 47,142 lux, p < 0.001). At 1 h after surgery, the decrease in photopic b-wave amplitude did not differ significantly between the two groups (-1.83 µV; 3D group, vs. -1.56 µV; standard group, p = 0.76). In exploratory analyses, ERG implicit time increased significantly in the standard group (p = 0.02) but remained stable in the 3D group (p = 0.24). At 1 month, an increase in macular thickness was observed only in the standard group (V1 265.9 ± 27.7 µm, V4 278.8 ± 34.9 µm; p = 0.003). Conclusions: Digital visualization significantly reduced intraoperative light exposure. However, no significant difference was observed for the primary endpoint of photopic ERG b-wave amplitude at 1 h postoperatively. Secondary findings regarding ERG implicit time and macular thickness should be considered exploratory and require confirmation in larger studies.},
}

@article {pmid42452475,
year = {2026},
author = {Asanad, S and Thomspon, J},
title = {Clinical Value of Optical Coherence Tomography Angiography in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {15},
number = {13},
pages = {},
doi = {10.3390/jcm15135013},
pmid = {42452475},
issn = {2077-0383},
abstract = {Background/Objectives: The utility of optical coherence tomography angiography (OCTA) for neovascular age-related macular degeneration (nAMD) remains unclear. The current study investigated the choroidal neovascularization (CNV) detection rate by OCTA in comparison with standard fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT). Methods: Subjects underwent multimodal imaging, including FA, SD-OCT, and OCTA imaging, which were compared. In patients with unilateral nAMD, the contralateral eye with dry AMD (n = 39) was included to determine imaging modality sensitivity and specificity. Eyes with inaccurate automated segmentation from retinal distortion were manually resegmented. Results: The diagnostic performance for nAMD was 86% sensitivity and 100% specificity by OCT (AUC: 0.93; 95% CI 0.87-0.99; p < 0.001); 82% sensitivity and 100% specificity by FA (AUC: 0.91; 95% CI 0.84-0.98; p < 0.001); and 68% sensitivity and 100% specificity by automatically segmented OCTA (AUC: 0.84; 95% CI 0.76-0.93; p < 0.001). OCTA diagnostic accuracy improved following manual resegmentation to 88% sensitivity and 100% specificity (AUC: 0.94; 95% CI 0.89-1.0; p < 0.001). Diagnostic accuracy of OCT combined with manually resegmented OCTA (AUC: 1.0; 95% CI 1.0-1.0; p < 0.001) was greater than that of OCT or FA combined (AUC: 0.96; 95% CI 0.92-1.0; p < 0.001) but both were very accurate. Conclusions: Manual segmentation of the OCTA images can help identify CNV in eyes otherwise undetected by automated segmentation algorithms due to errors in segmentation of retinal layers. Eyes with substantial elevation in one or more layers of the retina were most likely to benefit from resegmentation.},
}

@article {pmid42454894,
year = {2026},
author = {Sortino, R and González-Díez, A and Milla-Navarro, S and Martínez-Tambella, J and Paleo-García, V and Calatayud, E and de Saralegui, P and Opar, E and Claparols, À and Quintanilla, JA and Martínez-Soler, X and Riefolo, F and Matera, C and Hernando, J and Gomila, AMJ and Pérez-Batlle, G and Pereira, C and Camarero, N and Serra, C and Gómez-Santacana, X and Llebaria, A and Rovira, X and de la Villa, P and Gorostiza, P},
title = {Restoration of Saccadic Eye Movements and Visually Guided Behavior in Ambient White Light with Photoswitchable Small Molecules.},
journal = {Journal of the American Chemical Society},
volume = {},
number = {},
pages = {},
doi = {10.1021/jacs.5c18611},
pmid = {42454894},
issn = {1520-5126},
abstract = {Blinding diseases due to the degeneration of photoreceptors (PhRs), such as geographic atrophy (GA) secondary to dry age-related macular degeneration and retinitis pigmentosa (RP), leave the rest of the retinal circuitry largely intact, albeit unable to respond to light. Gene therapy has been able to revert PhR degeneration, but it can be applied only to a rare mutation affecting a small subset of RP patients. Alternatively, implanted electronic retinal prostheses aim at a larger population by electrically stimulating surviving neurons. However, the treatment is invasive and costly and provides limited resolution. Photopharmacology can develop photoswitchable small molecules to restore vision impairment by conferring light sensitivity to ion channels that are widely expressed in the remaining inner retinal neurons, and a first-in-human clinical trial is ongoing. Here, we have developed novel photoswitchable small-molecule ligands of metabotropic glutamate 6 (mGlu6) receptors, which are located exclusively at the dendrites of ON bipolar cells (postsynaptic to PhRs) and can leverage a privileged position to mimic physiological signals in the remnant retinal circuit. These photoswitchable ligands (prosthe6) thus act as "molecular prostheses" that can restore the light input to the retina via upstream-targeted control of the circuit after PhR degeneration. Prosthe6 compounds are allosteric, drug-like, water-soluble, and display outstanding in vitro properties including full efficacy, nanomolar potency, fast deactivation in ambient white light, and fast reactivation in the dark. In vivo experiments show that they readily recover the saccadic eye movements of blinded zebrafish larvae and restore the innate light-avoidance behavior in the mouse models of blindness (GA and RP). These effects are mediated by mGlu6 receptors in vivo. In addition, at least two compounds (prosthe6-12 and -15) can restore sight by topical administration and display promising safety properties to become potential drug candidates for sight restoration in patients with degenerative blinding diseases.},
}

@article {pmid42456794,
year = {2026},
author = {Papafotiou, E and Arampatzis, K and Ferreira, A and Koumpoulis, I and Tsinopoulos, I},
title = {Prognostic value of subretinal hyperreflective material as an imaging biomarker in the treatment of neovascular age-related macular degeneration: A systematic review.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.07.007},
pmid = {42456794},
issn = {1879-3304},
abstract = {Subretinal hyperreflective material (SHRM) is now recognized as a biomarker in neovascular age-related macular degeneration (nAMD), with potential prognostic value for visual and structural outcomes. We synthesize and critically evaluate the evidence on the prognostic role of SHRM characteristics in patients with nAMD. We conducted a systematic search of PubMed, Scopus and Web of Science for studies published between March, 2015, and March, 2025. Eligible studies included human participants with nAMD, under anti-vascular endothelial growth factor (VEGF) treatment, in which SHRM was assessed using optical coherence tomography and outcomes included best-corrected visual acuity (BCVA), fibrosis and macular atrophy. Thirty-three studies met the inclusion criteria. Most of the studies demonstrated a significant association between the presence of SHRM and worse BCVA over time, particularly correlated to SHRM thickness, width or persistence after anti-VEGF therapy. Well-defined and hyperreflective SHRM was repeatedly linked to poorer functional outcomes. Twelve studies reported SHRM as a strong predictor of subretinal fibrosis, with larger size, defined borders and persistence conferring the greatest risk. The relationship with macular atrophy was less clear; while some studies suggested that thicker or persistent SHRM increased the likelihood of atrophy, others found no association. Overall, the evidence suggests that SHRM is a strong imaging biomarker of poor prognosis in nAMD. While this review highlights consistent patterns, differences in how SHRM is measured remain a limitation. It will be important for future research to standardize SHRM assessment and establish its use in personalized treatment decisions.},
}

@article {pmid42439430,
year = {2026},
author = {Beqiri, S and Moxam, J and Pan, H and Kumar, BS and Berni, A and Shen, M and El-Mulki, OS and Herrera, G and Badla, O and Lam, W and Herrera, E and Ascioti, N and Le, VH and Trivizki, O and O'Brien, RC and Waheed, NK and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Impact of Swept-Source OCT Angiographic Scanning Speeds on the Detection of Choriocapillaris Flow Deficits in Eyes With AMD.},
journal = {Translational vision science & technology},
volume = {15},
number = {7},
pages = {16},
doi = {10.1167/tvst.15.7.16},
pmid = {42439430},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/diagnostic imaging ; Female ; Retrospective Studies ; *Macular Degeneration/physiopathology/diagnostic imaging ; Male ; Aged ; Regional Blood Flow/physiology ; *Fluorescein Angiography/methods ; Aged, 80 and over ; Prospective Studies ; Blood Flow Velocity ; Capillaries/physiopathology/diagnostic imaging ; },
abstract = {PURPOSE: The impact of swept-source optical coherence tomography angiography (SS-OCTA) scanning speeds (interscan times) on the quantification of choriocapillaris flow deficit percentages (CCFD%) was studied in eyes with nonexudative age-related macular degeneration.

METHODS: We conducted a retrospective review of 30 pairs of scans from 24 age-related macular degeneration subjects enrolled in an ongoing prospective SS-OCTA imaging study. Patients underwent imaging with same day scans at two scanning speeds: 100 kHz and 200 kHz (corresponding with 5.0-ms and 2.5-ms interscan times, respectively). Best practices for CC slab processing and CCFD quantification were implemented, and the compensation level was optimized for each scan. CCFD% measurements were obtained from the 3-mm and 5-mm fovea-centered circles.

RESULTS: The mean CCFD% measurements from the 3-mm fovea-centered circles for the 100-kHz and 200-kHz scans were 14.20% and 17.17% respectively, and 10.77% and 12.86% for the 5-mm circles. An agreement analysis showed a significant bias with mean values of 2.96% and 2.09% for the 3-mm and 5-mm circles. The limits of agreement extended predominantly in the positive direction with values of -1.96% to 7.89% and -0.60% to 4.78% in the 3-mm and 5-mm circles, respectively, that emphasize the systematically higher CCFD% recorded using the 200-kHz pattern. No confidence interval for the bias included zero, supporting the significant systematic bias across measurement strategies.

CONCLUSIONS: SS-OCTA scanning speeds have a significant impact on CCFD% quantification, with slower speeds yielding a lower CCFD%, likely due to the detection of slower CC flow, because of the higher associated interscan times.

TRANSLATIONAL RELEVANCE: When following and comparing choriocapillaris flow deficit percentage measurements over time, the same scanning speed should be used at each visit.},
}

Humans
*Tomography, Optical Coherence/methods
*Choroid/blood supply/diagnostic imaging
Female
Retrospective Studies
*Macular Degeneration/physiopathology/diagnostic imaging
Male
Aged
Regional Blood Flow/physiology
*Fluorescein Angiography/methods
Aged, 80 and over
Prospective Studies
Blood Flow Velocity
Capillaries/physiopathology/diagnostic imaging

@article {pmid42441062,
year = {2026},
author = {Wang, Y and Zhang, W and Cheng, F and Wang, J and Xiao, K and Wang, D and Zhao, X and Zou, R and Yao, Q},
title = {Mannose-modified miR-223 nanoparticles remodel pathological microenvironment to suppress inflammation and angiogenesis for neovascular AMD therapy.},
journal = {International journal of pharmaceutics: X},
volume = {12},
number = {},
pages = {100589},
pmid = {42441062},
issn = {2590-1567},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly, with neovascular AMD (nAMD) driven by choroidal neovascularization (CNV), persistent inflammation, and oxidative stress. Although combinatorial strategies targeting these pathological factors hold therapeutic promise, their clinical translation is constrained by the lack of effective delivery systems. In this study, we designed a mannose-functionalized poly(aspartic acid)-based nanocarrier bearing quaternary ammonium and boronic acid groups (MDA/QPABA) for the targeted delivery of microRNA-223 (miR-223). The system exploits charge-driven self-assembly to form stable nanoparticles with high loading efficiency, favorable colloidal stability, and tunable surface properties. The mannose moieties enable specific recognition by mannose receptors on target cells, facilitating cellular uptake and subsequent lysosomal escape. The resulting MDA/QPABA/miR-223 nanoparticles demonstrated pronounced anti-inflammatory, antioxidant, and anti-angiogenic activities in vitro. In a laser-induced CNV mouse model, they effectively reduced inflammatory and angiogenic cytokines, suppressed pathological neovascularization, restored retinal and choroidal structure, and preserved photoreceptor function, with an excellent biosafety. These findings highlight the potential of rationally engineered poly(aspartic acid)-based nanoarchitectures with tailored surface chemistry and biointerfacial properties for multifunctional nucleic acid delivery in nAMD therapy.},
}

@article {pmid42445785,
year = {2026},
author = {Wang, Y and Wan, X},
title = {Metabolic vulnerability, genetic susceptibility, and incident age-related eye diseases: a prospective cohort study.},
journal = {Frontiers in nutrition},
volume = {13},
number = {},
pages = {1840459},
pmid = {42445785},
issn = {2296-861X},
abstract = {BACKGROUND: Metabolic dysregulation is increasingly recognized as a systemic process contributing to chronic disease development, yet prospective evidence linking integrated metabolic vulnerability to age-related eye diseases remains limited. We investigated whether a biomarker-based metabolic vulnerability index (MVX) was associated with incident age-related ocular diseases and whether joint consideration of MVX and genetic susceptibility may help characterize relative risk patterns.

METHODS: A prospective population-based cohort of 206,311 participants from the UK Biobank was analyzed. MVX was evaluated as the primary exposure. Incident age-related macular degeneration (AMD), cataract, diabetic retinopathy (DR), and glaucoma were ascertained as outcomes. Associations were examined using Cox proportional hazards models, with hazard ratios (HRs) and 95% confidence intervals (CIs) estimated per 1-standard deviation (SD) increase in MVX. As secondary exploratory analyses, polygenic risk score (PRS) analyses were performed to explore whether metabolic vulnerability and genetic susceptibility jointly characterized relative risk patterns.

RESULTS: During follow-up, 4,144 participants developed AMD, 13,574 cataract, 1,483 DR, and 5,525 glaucoma. After multivariable adjustment for demographic, socioeconomic, clinical, and lifestyle factors, each 1-SD increase in MVX was associated with higher risks of incident AMD (HR = 1.07; 95% CI: 1.03-1.11), cataract (HR = 1.04; 95% CI: 1.02-1.06), and DR (HR = 1.11; 95% CI: 1.05-1.18), whereas no significant association was observed for glaucoma (HR = 1.00; 95% CI: 0.97-1.03). In joint analyses, individuals with both high genetic risk and elevated MVX exhibited the greatest risks of AMD (HR = 2.32; 95% CI: 2.01-2.67), cataract (HR = 1.62; 95% CI: 1.49-1.76), and DR (HR = 3.84; 95% CI: 2.91-5.06), compared with those with low genetic risk and low MVX.

CONCLUSION: These findings suggest that MVX may be relevant to population-level patterns of risk for several age-related eye diseases. However, further studies are needed to determine whether MVX provides meaningful predictive value or clinical utility beyond conventional risk factors.},
}

@article {pmid42448079,
year = {2026},
author = {Sakamoto, T and Kadomoto, S and Nakanishi, Y and Muraoka, Y and Hata, M and Ooto, S and Tsujikawa, A},
title = {In Vivo Quantification of Bruch's Membrane Changes in Angioid Streaks and Neovascular AMD Using Multimodal Imaging.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.07.011},
pmid = {42448079},
issn = {1879-1891},
abstract = {PURPOSE: To investigate Bruch's membrane (BrM) morphology in angioid streak (AS)-associated macular neovascularization (MNV) and neovascular age-related macular degeneration (nAMD) using multimodal imaging.

DESIGN: Retrospective clinical cohort study.

SUBJECTS: Treatment-naïve eyes with MNV secondary to AS or nAMD that achieved a dry macula after three loading intravitreal anti-vascular endothelial growth factor (VEGF) injections.

METHODS: Baseline indocyanine green angiography (ICGA) images obtained before anti-VEGF treatment were used to measure axial length-corrected MNV area and identify late-phase speckled hypofluorescent areas (SHA). Optical coherence tomography (OCT) images after dry macula achievement were used to assess central foveal thickness (CFT), subfoveal choroidal thickness (SCT), fibrovascular pigment epithelial detachment (PED) thickness, BrM undulation, and a newly defined BrM reflectivity index (BRI) calculated from intensity-normalized images. Group comparisons assessed BrM-related biomarker differences, and receiver operating characteristic (ROC) analyses evaluated their diagnostic performance.

MAIN OUTCOME MEASURES: Differences in ICGA- and OCT-derived findings between AS-associated MNV and nAMD, including SHA, BrM undulation, and BRI, and the diagnostic performance of BRI and BrM undulation in differentiating AS-associated MNV from nAMD.

RESULTS: Twenty-five eyes with AS and 32 eyes with nAMD were analyzed. Among eyes with available ICGA, MNV area was larger in AS than in nAMD (5.34 ± 3.29 mm² vs 3.45 ± 1.22 mm², P = 0.005), and late-phase SHA was more frequent in AS (86.4% vs 18.8%, P<0.001). CFT and fibrovascular PED thickness did not differ significantly, whereas SCT was lower in AS-associated MNV than in nAMD (166.0 ± 67.1 μm vs. 217.2 ± 112.0 μm; P = 0.049). BrM undulation was more common in the AS group (24.0% vs. 3.1%, P=0.036). BRI was higher in AS than in nAMD (0.905 ± 0.148 vs 0.663 ± 0.169, P<0.001). The ROC curve for BRI showed an area under the curve of 0.850 (95% confidence interval, 0.754-0.946) with an optimal cutoff of 0.749, yielding 0.880 sensitivity and 0.656 specificity.

CONCLUSIONS: Compared with nAMD, AS-associated MNV showed distinct ICGA and OCT features, including larger MNV area, more frequent late-phase SHA and BrM undulation, and higher BRI after anti-VEGF loading. These findings may reflect BrM alterations associated with calcification and mechanical instability. BrM-derived ICGA and OCT biomarkers may help characterize AS pathophysiology and differentiate AS-associated MNV from nAMD.},
}

@article {pmid42448244,
year = {2026},
author = {Paracini, M and Radwan, A and Peron, G},
title = {Food-derived bioactive compounds in ocular diseases: molecular mechanisms, clinical evidence, and translational challenges.},
journal = {The Journal of nutritional biochemistry},
volume = {},
number = {},
pages = {110465},
doi = {10.1016/j.jnutbio.2026.110465},
pmid = {42448244},
issn = {1873-4847},
abstract = {Age-related and chronic ocular diseases share common underlying mechanisms including oxidative stress, low-grade inflammation, mitochondrial dysfunction, and neurodegeneration. In parallel with advances in conventional therapies, interest in bioactive compounds derived from dietary sources (nutraceuticals) has increased due to their multiple molecular effects and potential to modulate the pathways leading to ocular disease. In this work, the current evidence for major classes of nutraceuticals, including carotenoids, polyphenols, organosulfur compounds, and other plant-derived metabolites was examined, with emphasis on their pharmacodynamic properties, mechanisms of action, and clinical relevance in ocular health. Mechanistic insights from in vitro and animal models were integrated with findings from clinical studies, highlighting molecular targets such as Nrf2-mediated antioxidant responses, NF-κB-driven inflammation, angiogenic signalling, and mitochondrial function. Carotenoids including lutein and zeaxanthin show the most consistent clinical evidence, particularly in increasing macular pigment optical density and reducing progression to advanced macular degeneration. In contrast, other carotenoids and most polyphenols including flavonoids, curcumin, and resveratrol demonstrate promising anti-inflammatory and anti-angiogenic effects primarily supported by preclinical data, with limited and heterogeneous clinical validation. Overall, current evidence suggests that nutraceuticals may have different effects and applicability in managing ocular diseases, although the majority of compounds discussed remain supported only by mechanistic and preclinical data, instead of clinical evidence. Future progress will require rigorously designed clinical studies, improved pharmacokinetic characterization, and precise stratification of patient populations to establish their therapeutic efficacy and relevance.},
}

@article {pmid42448736,
year = {2026},
author = {Ma, CC and Lu, CC and Chien, WC and Chung, CH and Weng, TH and Tsai, CT and Chen, JT and Chen, YH and Chen, CL},
title = {Association between silymarin and age-related macular degeneration in patients with liver dysfunction: a nationwide cohort study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-62141-x},
pmid = {42448736},
issn = {2045-2322},
support = {MND-MAB-D-112114, MND-MAB-D-114117, MND-MAB-D-115128//Ministry of National Defense/ ; TSGH-E-112242, TSGH_E_113268, TSGH_E_114266, TSGH_E_115268//Tri-Service General Hospital Research Foundation/ ; },
abstract = {We investigated the association between silymarin use and age-related macular degeneration (AMD) in patients with liver dysfunction using data from the Taiwan National Health Insurance Research Database from 2000 to 2021. Patients with liver dysfunction were classified into silymarin users and non-users, followed by 1:4 propensity score matching. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs), and Kaplan-Meier analysis was performed to compare cumulative AMD incidence. AMD subtype analyses and lag-time sensitivity analyses were also conducted. A total of 4,965 silymarin users and 19,860 matched non-users were included. The incidence of AMD was lower in the silymarin group than in the non-silymarin group (7.33% vs. 9.24%, P < 0.001). Kaplan-Meier analysis showed a lower cumulative incidence of AMD among silymarin users (log-rank P < 0.001). Silymarin use was associated with a lower risk of AMD (aHR = 0.846, P = 0.001), including both wet AMD (aHR = 0.772, P < 0.001) and dry AMD (aHR = 0.852, P = 0.004). A lower risk of transition from dry to wet AMD was also observed among silymarin users. Similar associations were identified in lag-time sensitivity analyses. Further prospective studies are warranted to clarify this association and its potential clinical implications.},
}

@article {pmid42448987,
year = {2026},
author = {Mira, F and Donato, S and Vaz, F and Madeira, F and Picoto, M and Mendes, A and Beato, J and Torres-Costa, S and Pinto, C and Oliveira, N and Feliciano, S and Lume, M and Carreiro, R and Couto, M and Carneiro, Â},
title = {Real-World Outcomes of Faricimab in Patients with Highly Refractory Neovascular Age-Related Macular Degeneration in Portugal: The REVEAL Study.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42448987},
issn = {2193-8245},
support = {#SL45612//Roche Farmacêutica Química Lda./ ; },
abstract = {INTRODUCTION: Management of highly refractory exudative neovascular age-related macular degeneration (nAMD) remains challenging when multiple antivascular endothelial growth factor (VEGF) therapies fail to control the disease. Faricimab, through dual inhibition of VEGF-A and angiopoietin-2, may represent a potential therapeutic alternative for this difficult-to-treat population. However, real-world evidence in highly refractory nAMD remains limited and is lacking in the Portuguese population.

METHODS: This multicenter, retrospective, real-world study included patients with nAMD highly refractory to previous anti-VEGF therapies who were treated with faricimab and followed for at least 6 months. Functional and anatomical outcomes were assessed, including changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), and evolution of intraretinal fluid (IRF) and subretinal fluid (SRF).

RESULTS: A total of 46 eyes from 40 patients were included, characterized by a long-standing disease (median [25th percentile (P25); 75th percentile (P75)] duration, 5.0 [3.0; 6.0] years) and a high prior treatment burden (32.0 [24.0; 45.8] anti-VEGF injections and median treatment interval of 4.0 [4.0; 6.0] weeks). After faricimab, functional stability was observed (median change in BCVA of 0.0 [-0.1; 0.1] logMAR). Anatomical outcomes showed improvement, with a median reduction in CST of -12 [-58; 7] µm and complete SRF resolution in 47.8% of eyes. Median treatment intervals of 8.0 [6.0-10.0] weeks were achieved, representing a twofold increase in the median treatment interval.

CONCLUSIONS: In this real-world study of highly refractory nAMD, faricimab was associated with stabilization of functional outcomes and improvement in anatomical outcomes over short- to mid-term follow-up, alongside a twofold increase in treatment-interval length in routine clinical practice. These findings support the clinical relevance of inhibiting angiopoietin-2 (Ang-2) and represent the first evaluation conducted in routine clinical practice in Portugal, with potential implications for treatment burden and patient adherence.},
}

@article {pmid42449255,
year = {2026},
author = {Okutucu, M and Arpa, M},
title = {Evaluation of serum semaphorin-3A and interleukin 6 levels in patients with neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-05128-6},
pmid = {42449255},
issn = {1471-2415},
abstract = {PURPOSE: To determine whether serum semaphorin 3 A (Sema3A) and interleukin 6 (IL-6) play a role in the common etiopathogenesis of nAMD and nAMD-associated systemic diseases by evaluating these mediators levels.

METHODS: This prospective case-control study included 74 patients divided into nAMD (n = 33) and a control group (n = 41). Serum Sema3A and IL-6 levels were analyzed using the enzyme-linked immunosorbent assay.

RESULTS: The nAMD group had a statistically higher IL-6 level [5,9 (1-16,9) pg/mL], compared to the control group [1,5 (0,38 - 2,96) pg/mL] (p < 0.001). On the other hand, the Sema3A level of the nAMD group was lower at [26,3 (11,5-100) ng/mL] compared to the control group at [44,7 (16,8-100) ng/mL] (p < 0.001). The IL-6 level in the hypertension (+) group [2,5 (0,5-16,9) pg/ml] was significantly higher than that in the hypertension (-) group [1,7 (0,4-15,3) pg/ml] (p < 0.001). No significant difference was found between the hypertension (+) and hypertension (-) groups in terms of SEMA3A level. There was a negative correlation between serum SEMA3A and serum IL-6 levels of the whole participants (p < 0.001, r=-0.471).

CONCLUSIONS: Decreased levels of the anti-inflammatory and anti-angiogenic mediator Sema3A and increased levels of inflammatory mediator IL-6 detected in nAMD suggest that these molecules may play a role in systemic manifestations of this syndrome, such as inflammation, cardiovascular diseases, atrial fibrillation, and Alzheimer's disease.

CLINICAL TRIAL NUMBER: Not applicable.},
}

@article {pmid42449377,
year = {2026},
author = {Zhu, X and Wordsworth, S and Lee, CN and Wafa, HA and Wang, Y and Desai, R and Ramazzotto, L and Reeves, BC and Jackson, TL and Dakin, H and , },
title = {EQ-5D vision bolt-on in macular degeneration: associations with visual measures and effect on utility differences and cost-effectiveness of stereotactic radiotherapy.},
journal = {Health and quality of life outcomes},
volume = {24},
number = {1},
pages = {},
pmid = {42449377},
issn = {1477-7525},
mesh = {Humans ; Cost-Benefit Analysis ; Female ; *Visual Acuity ; Male ; *Macular Degeneration/drug therapy/radiotherapy ; Aged ; Cost-Effectiveness Analysis ; United Kingdom ; *Quality of Life ; Surveys and Questionnaires ; *Radiosurgery/economics/methods ; Double-Blind Method ; Ranibizumab/therapeutic use/economics ; Quality-Adjusted Life Years ; Angiogenesis Inhibitors/therapeutic use/economics ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Patient Reported Outcome Measures ; Aged, 80 and over ; },
abstract = {BACKGROUND: The UK STAR trial [Stereotactic Radiotherapy (SRT) for neovascular age-related macular degeneration (nAMD)] compared 16-Gray SRT (n = 274) with double-masked sham SRT (n = 137) in participants with chronic active nAMD. SRT reduced intravitreal anti-vascular endothelial growth factor (VEGF) re-treatments over two years of pro re nata ranibizumab, followed by two years of routine care. However, this resulted in worse best-corrected visual acuity (BCVA) in Years 3 and 4. This paper describes: associations between the EQ-5D vision bolt-on and visual acuity and patient-reported outcome measures; the impact of SRT on utilities with and without vision bolt-on; how the vision bolt-on affects the cost-effectiveness of SRT plus anti-VEGF versus anti-VEGF alone.

METHODS: Using data from the entire STAR trial cohort, we compared mean BCVA, EQ-5D-5L, and Visual Function Questionnaire-25 (VFQ-25) scores across the three levels of the EQ-5D vision bolt-on. We examined the relationship between BCVA and EQ-5D (with/without the bolt-on) and VFQ-25. An economic evaluation estimated the cost-effectiveness of SRT from a UK national health service perspective over two years and over four years. This used prospective data on EQ-5D-5L and eye-related direct healthcare use.

RESULTS: Participants reporting vision problems on the bolt-on had significantly worse BCVA, EQ-5D-5L, and VFQ-25 scores than those who did not. EQ-5D utilities (with and without the bolt-on) increased with BCVA but showed weaker correlations than VFQ-25 composite scores. Quality-adjusted life years (QALYs) did not differ significantly between treatment groups, with or without the bolt-on. The economic evaluation suggested SRT would reduce healthcare costs by £404 (95% CI: -£1282 to £2092) per patient at a four-year time horizon. The probability of SRT plus anti-VEGF being cost-effective at a £20,000 per QALY threshold was 65% at a four-year time horizon. Sensitivity analyses confirmed the robustness of incorporating the vision bolt-on did not alter the cost-effectiveness conclusion.

CONCLUSIONS: Resource use data from the trial and routine follow-up could be used for future economic models. The vision bolt-on captured quality of life differences between participants but may not be sufficiently responsive to visual acuity decline in trials where only one eye is treated.

TRIAL REGISTRATION: ISRCTN12884465, registration date 01/12/2014.},
}

Humans
Cost-Benefit Analysis
Female
*Visual Acuity
Male
*Macular Degeneration/drug therapy/radiotherapy
Aged
Cost-Effectiveness Analysis
United Kingdom
*Quality of Life
Surveys and Questionnaires
*Radiosurgery/economics/methods
Double-Blind Method
Ranibizumab/therapeutic use/economics
Quality-Adjusted Life Years
Angiogenesis Inhibitors/therapeutic use/economics
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Patient Reported Outcome Measures
Aged, 80 and over

@article {pmid42449957,
year = {2026},
author = {Siqueira, RC},
title = {Molecular Mechanisms of Photobiomodulation in Retinal Diseases: Cytochrome c Oxidase, Mitochondrial Bioenergetics and Cytoprotective Signalling.},
journal = {International journal of molecular sciences},
volume = {27},
number = {13},
pages = {},
doi = {10.3390/ijms27135683},
pmid = {42449957},
issn = {1422-0067},
mesh = {Humans ; *Mitochondria/metabolism/radiation effects ; Animals ; *Signal Transduction/radiation effects ; *Electron Transport Complex IV/metabolism ; *Energy Metabolism/radiation effects ; *Retinal Diseases/metabolism/therapy/radiotherapy ; *Low-Level Light Therapy/methods ; },
abstract = {Photobiomodulation (PBM) is a non-invasive therapeutic strategy that uses red and near-infrared (NIR) light in the 590-950 nm range to modulate the cellular and molecular pathways involved in retinal homeostasis. At the molecular level, PBM acts primarily through photon absorption by cytochrome c oxidase (CcO, complex IV of the mitochondrial electron transport chain), whose four metal centres-two copper (CuA and CuB) and two heme groups (heme a and heme a3)-absorb light across approximately 600-1000 nm. Photon capture promotes photodissociation of inhibitory nitric oxide (NO) from the binuclear CuB-heme a3 centre, accelerates electron transfer, restores the proton-motive force and increases ATP synthesis. These primary events trigger a coordinated molecular programme that includes (i) transient mitochondrial reactive oxygen species (ROS) bursts that activate the Nrf2/Keap1/ARE axis and upregulate phase II antioxidant enzymes (HO-1, NQO1, GCLC, SOD2, catalase, GPx); (ii) calcium- and cAMP-dependent secondary signalling that converges on PI3K/Akt, MAPK/ERK, AMPK and mTOR pathways; (iii) suppression of NF-κB-driven cytokine production (TNF-α, IL-1β, IL-6) and of NLRP3 inflammasome activation; (iv) downregulation of the HIF-1α/VEGF axis, particularly at 590 nm; (v) anti-apoptotic remodelling of the Bcl-2/Bax ratio with reduced cytochrome c release and caspase-3/9 activation; and (vi) PGC-1α/TFAM/NRF1-driven mitochondrial biogenesis, alongside restoration of fission/fusion homeostasis (Drp1, Mfn1/2, Opa1) and PINK1/Parkin-mediated mitophagy. Wavelength specificity has a defined molecular basis: 590 nm modulates VEGF signalling and RPE pump activity, 660 nm interacts with the CuB centre and enhances O2 binding at CcO, and 850 nm is absorbed by CuA and supports electron entry into complex IV. A second molecular axis is the bidirectional crosstalk between PBM and the circadian system: mitochondrial respiration, ATP turnover and CcO activity oscillate over the 24 h cycle under the control of the BMAL1/CLOCK and PER/CRY core machinery, the NAD[+]/SIRT1-SIRT3 axis and REV-ERBα. Preliminary preclinical and human observations suggest that NIR-induced bioenergetic and functional gains may be coupled to this rhythm, with greater benefit reported when light is delivered in the morning window (≈08:00-11:00); this time dependence should be regarded as an emerging hypothesis rather than an established clinical principle. The clinical evidence is unevenly developed across indications. It is most robust for non-exudative age-related macular degeneration, where multiwavelength PBM (590/660/850 nm; Valeda Light Delivery System) has shown disease-modifying potential in randomized controlled trials (LIGHTSITE I-III and the LIGHTSITE IIIB extension), with sustained BCVA gains and reduced incidence of geographic atrophy over 24 months and beyond. Evidence for retinitis pigmentosa, central serous chorioretinopathy and, with red-light monotherapy, childhood myopia is at present limited to small or short-term studies and remains preliminary. This narrative review synthesizes the molecular machinery engaged by PBM, integrates clinical findings across retinal diseases and discusses how chronotherapeutic delivery of light, aligned with the molecular clock, may further optimize therapeutic efficacy.},
}

Humans
*Mitochondria/metabolism/radiation effects
Animals
*Signal Transduction/radiation effects
*Electron Transport Complex IV/metabolism
*Energy Metabolism/radiation effects
*Retinal Diseases/metabolism/therapy/radiotherapy
*Low-Level Light Therapy/methods

@article {pmid42435833,
year = {2026},
author = {Gagliardi, OM and Sahoo, NK and Hasan, N and Gregori, G and Peña, DF and Iannetta, D and Chhablani, J},
title = {Tomographic predictors of foveal versus extrafoveal atrophy onset in intermediate age-related macular degeneration.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.07.010},
pmid = {42435833},
issn = {1879-1891},
abstract = {PURPOSE: To evaluate whether baseline foveal tomographic lesions are associated with foveal-first versus extrafoveal-first onset of complete retinal pigment epithelial and outer retinal atrophy (cRORA) in intermediate age-related macular degeneration (iAMD).

DESIGN: Retrospective cohort study.

PARTICIPANTS: A total of 129 eyes of 89 patients with iAMD developing cRORA.

METHODS: Consecutive eyes with iAMD progressing to cRORA were identified through back-tracking grading on spectral-domain optical coherence tomography. Eligible eyes had at least 3 years of follow-up before cRORA onset, with no pre-cRORA inter-visit gap exceeding 6 months. The foveal region was operationally defined as the 1-mm Early Treatment Diabetic Retinopathy Study central subfield. Baseline foveal lesions included soft drusen, subretinal drusenoid deposits (SDD), drusenoid pigment epithelial detachment (dPED), acquired vitelliform lesions (AVL), and incomplete retinal pigment epithelium and outer retinal atrophy (iRORA). Hyperreflective foci (HRF) were recorded as present/absent.

MAIN OUTCOME MEASURES: Foveal-first versus extrafoveal-first cRORA onset; interval-censored time from extrafoveal cRORA onset to foveal involvement.

RESULTS: Over a mean follow-up of 10.4 ± 3.4 years, 108 eyes (83.7%) developed foveal cRORA. cRORA onset was foveal-first in 60 eyes (46.5%) and extrafoveal-first in 69 eyes (53.5%). Onset pattern differed across baseline lesions (p < 0.001). SDD and soft drusen were more frequently associated with extrafoveal-first onset (20/22 [91%] and 25/40 [63%]), whereas AVL, iRORA, and dPED were more frequently associated with foveal-first onset (16/23 [70%], 7/10 [70%], and 20/34 [59%]). Among 48 extrafoveal-first eyes that reached the fovea, time to foveal involvement was similar across lesion types (median, 1.5-1.8 years; p = 0.97). Compared with soft drusen, the time to foveal cRORA was shorter for iRORA, dPED, and AVL (time ratios: 0.12, 0.40, and 0.50; 95% CIs: 0.06-0.23, 0.30-0.55, and 0.35-0.71). Foveal HRF independently predicted faster progression (time ratio, 0.66; 95% CI, 0.51-0.85; p = 0.001).

CONCLUSION: In iAMD eyes progressing to cRORA, distinct tomographic lesions at the fovea were associated with a different propensity to foveal-first versus extrafoveal-first atrophic onset. Once extrafoveal cRORA was established, time to foveal involvement did not differ across tomographic lesions. These findings may inform lesion-specific risk stratification for emerging dry AMD therapies.},
}

@article {pmid42437111,
year = {2026},
author = {Tandon, NR and Vasquez, E and Csaky, KG},
title = {Test-Retest Repeatability of a Novel Photopic Microperimetry Approach in Patients with Geographic Atrophy.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101267},
pmid = {42437111},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate test-retest repeatability of novel focal photopic microperimetry approach targeting central 1 mm of the fovea and explore its relationships with geographic atrophy (GA) lesion area and other visual function metrics.

DESIGN: A prospective, single arm, observational study.

SUBJECTS: Participants with nonsubfoveal GA as determined by spectral-domain OCT and fundus autofluorescence.

METHODS: Twelve participants (17 eyes) performed focal photopic tests using a 45-loci focal grid (0.5° spacing; Goldmann II stimuli) on Nidek MP-3, along with other visual function assessments. To assess test-retest repeatability of MP-3, 2 tests up to 4 weeks apart were performed. The interval was short relative to expected GA progression, and thus measurements are interpreted as reflecting test-retest repeatability.

MAIN OUTCOME MEASURES: Coefficient of repeatability (CoR), intraclass correlation coefficient (ICC), and Bland-Altman were analyzed for mean sensitivity (MS) and point-wise sensitivity (PWS). Correlations of adjusted MS (excluding floor effect) with GA lesion size, best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), and contrast sensitivity were also analyzed.

RESULTS: Focal photopic MP-3 showed good test-retest repeatability with CoR of MS at 2.42 dB (intraclass correlation coefficient [ICC] = 0.98) and CoR of PWS at 8.2 dB (ICC = 0.89). Excluding the floor effect improved the CoR of MS and PWS to 2.03 dB and 7.06 dB, respectively. Mean test duration was 4.33 minutes per eye with fixation stability >89%. Structure-function analysis showed weak correlation between GA lesion size and adjusted MS (P = 0.05; R [2] = 0.44). Adjusted MS showed a significant correlation with LLVA (P = 0.001) and low-luminance quick contrast sensitivity function (qCSF) (P = 0.01), a weak association with qCSF (P = 0.05), but no correlation with BCVA.

CONCLUSIONS: Focal photopic microperimetry using Goldmann II stimuli provides a highly repeatable measure of central cone-mediated function in patients with nonsubfoveal GA. Mean sensitivity demonstrated high repeatability and supports its use as a robust, clinically relevant endpoint for longitudinal and interventional studies, while PWS may provide spatial information for deeper structure-function analyses. Weak associations with GA lesion size and BCVA suggest that conventional measures may underestimate visual impairment, highlighting the value of focal photopic microperimetry within central 1 mm region as a sensitive, patient-centered outcome in age-related macular degeneration.

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

@article {pmid42437114,
year = {2026},
author = {Gao, Y and Xu, J and Yu, J and Zhang, Y 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 = {Shared Genetic Architecture and Multidimensional Modifiable Correlates between Myopia and Retinal-Optic Nerve Diseases.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101277},
pmid = {42437114},
issn = {2666-9145},
abstract = {PURPOSE: This study aimed to characterize the shared genetic architecture and modifiable correlates between myopia and retinal-optic nerve diseases (RONDs).

DESIGN: Genetic pleiotropy analysis and population-based cohort study.

PARTICIPANTS: A total of 81 491 UK Biobank participants and summary statistics from large-scale genome-wide association studies were included.

METHODS: We examined associations between myopia and 5 common RONDs using population-based analyses of prevalent and incident outcomes, followed by cross-trait genetic analyses, locus-level annotation, colocalization, and enrichment analyses. Among myopic individuals, modifiable correlates and gene-environment interactions were evaluated, and Mendelian randomization was used as complementary evidence for selected associations.

MAIN OUTCOME MEASURES: Myopia and RONDs.

RESULTS: The primary findings were that, in baseline prevalent analyses, myopia was associated with higher risks of retinal detachment (RD) and primary open-angle glaucoma (POAG), but a lower risk of primary angle-closure glaucoma (PACG), with evident risk gradients across myopia severity, especially for RD. Diabetic retinopathy (DR) risk estimates were <1.0 across myopia severity categories but were not statistically significant. A U-shaped association was observed between refractive status and age-related macular degeneration, with elevated risk in both high myopia and hyperopia. Incident analyses during follow-up showed broadly consistent patterns. As supportive genetic evidence, cross-trait analyses revealed significant genetic correlations and overlaps between myopia and RONDs, identifying 66 pleiotropic loci and 115 candidate genes, with enrichment in immune-inflammatory, receptor-mediated signaling, and retinal developmental pathways. Among myopic individuals, exploratory analyses further showed that prevalent myopia-ROND comorbidity was associated with various modifiable correlates spanning health status, lifestyle, diet, mental health, sleep patterns, and medication use, and that 7 environmental factors interacted with 5 pleiotropic variants. Mendelian randomization analyses provided complementary and hypothesis-supporting evidence consistent with a positive association of myopia with RD and an inverse association with PACG, whereas findings for DR and POAG required more cautious interpretation because of pleiotropy or heterogeneity.

CONCLUSIONS: This study reveals a shared genetic architecture and identifies modifiable correlates linking myopia to five common RONDs. These findings provide new insights into shared susceptibility patterns and offer a framework for future mechanistic, validation, and prevention-oriented research in myopic populations.

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

@article {pmid42437118,
year = {2026},
author = {Wu, A and Au, A and Hanson, J and Yamamoto, M and Cheng, J and Lee, S and Lior, TE and Avram, O and Sadda, SR and Coyne, AB and Acharya, NR and Madow, B and Chiang, JN and Tsui, E},
title = {Quantitative Analysis of Retinal Fluid by a Deep Learning Model in Uveitic Macular Edema.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101241},
pmid = {42437118},
issn = {2666-9145},
abstract = {OBJECTIVE: To assess whether artificial intelligence (AI)-derived fluid volume provides prognostic value for visual outcomes in uveitic macular edema (UME) and to compare model performance to central macular thickness (CMT) measurements alone.

DESIGN: Secondary subanalysis of patients with UME in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) clinical trial using a deep learning segmentation model trained on patients with age-related macular degeneration (AMD) and patients with retinal vein occlusion.

PARTICIPANTS: Patients with UME secondary to noninfectious uveitis from the FAST Uveitis Trial.

METHODS: A 2-dimensional U-Net model, trained on patients with AMD and retinal vein occlusion using the RETOUCH data set, was applied to segment intraretinal fluid (IRF) and subretinal fluid (SRF) in Heidelberg Spectralis OCT scans from the FAST Uveitis Trial. Model performance was validated against binary fluid gradings. Linear mixed-effects models evaluated fluid resolution during treatment. Likelihood ratio tests and leave-one-subject-out cross-validation assessed whether baseline IRF and SRF volumes provided improved model fit for visual acuity (VA) change over 6 months of treatment compared to CMT alone.

MAIN OUTCOME MEASURES: Segmentation accuracy, correlation of fluid volume with VA, and association of VA change with baseline fluid volumes and CMT versus CMT only.

RESULTS: The model achieved Dice scores of 0.61 for IRF and 0.74 for SRF on the RETOUCH data set. In the FAST data set, fluid segmentation correlated with binary gradings (biserial correlation: IRF 0.39, SRF 0.63; Mann-Whitney U test: IRF and SRF P < 0.01). Longitudinal fluid modeling showed no significant treatment differences in IRF or SRF resolution. However, baseline IRF volume had a significant interaction with treatment assignment (P = 0.02) when modeling VA change, suggesting that baseline IRF was more strongly associated with worse outcomes in the methotrexate group than the mycophenolate mofetil group. The likelihood ratio test confirmed that adding IRF and SRF improved fit over a model using CMT alone (P < 0.01) while leave-one-subject-out cross-validation showed a small, nonsignificant difference in prediction error.

CONCLUSIONS: Artificial intelligence-based segmentation of IRF and SRF enabled quantitative fluid measurements in UME and may provide additional prognostic signal for VA change in UME compared to CMT alone, although larger cohorts will be needed to determine the magnitude of generalizable performance gains, if any. These findings support integrating AI-driven fluid analysis in clinical workflows and suggest that future clinical trials should consider stratifying by baseline fluid characteristics using AI fluid analysis.

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

@article {pmid42437329,
year = {2026},
author = {Fu, L and Huang, L and Guo, R and Wu, L and Zeng, X and Fu, Z},
title = {Study on retinal pharmacokinetic characteristics and precision drug administration strategy in patients with fundus diseases.},
journal = {Pakistan journal of pharmaceutical sciences},
volume = {39},
number = {9},
pages = {2825-2836},
doi = {10.36721/PJPS.2026.39.9.263.1},
pmid = {42437329},
issn = {3105-9686},
mesh = {Humans ; Female ; Blood-Retinal Barrier/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Retrospective Studies ; *Diabetic Retinopathy/drug therapy/metabolism/diagnostic imaging ; Male ; Aged ; Tomography, Optical Coherence ; Precision Medicine ; Middle Aged ; *Retina/metabolism ; Retinal Pigment Epithelium/metabolism ; Aged, 80 and over ; },
abstract = {BACKGROUND: Fundus diseases are major causes of irreversible visual impairment. Retinal pharmacokinetic behavior may differ between diabetic retinopathy (DR) and age-related macular degeneration (AMD), but disease-specific dosing principles remain insufficiently defined.

OBJECTIVES: Disease-stratified retinal pharmacokinetic characteristics were evaluated, and a precision drug administration strategy for patients with fundus diseases was developed.

METHODS: Blood-retinal barrier (BRB) cell models, retinal organoids, retinal pigment epithelium (RPE) models, optical coherence tomography (OCT), serum biomarkers and clinical records were integrated. A retrospective, controlled clinical analysis was performed in patients with DR or AMD, in accordance with ethics approval No. 20240923.

RESULTS: DR was characterized by greater barrier permeability and transporter-related retention, whereas AMD was characterized by lipid-associated RPE dysfunction and restricted trans-retinal penetration. The DR model predicted retinal peak concentration with R2 = 0.89, and the AMD model predicted drug half-life with 86% accuracy. Precision administration was associated with reduced injection frequency in DR and AMD and improved anatomical and visual outcomes.

CONCLUSION: Disease-specific retinal pharmacokinetic differences support individualized dosing strategies for fundus diseases. The proposed platform provides a practical framework for precision anti-VEGF therapy and targeted retinal drug delivery.},
}

Humans
Female
Blood-Retinal Barrier/metabolism
*Macular Degeneration/drug therapy/metabolism
Retrospective Studies
*Diabetic Retinopathy/drug therapy/metabolism/diagnostic imaging
Male
Aged
Tomography, Optical Coherence
Precision Medicine
Middle Aged
*Retina/metabolism
Retinal Pigment Epithelium/metabolism
Aged, 80 and over

@article {pmid42435130,
year = {2026},
author = {Panos, GD},
title = {Letter to the Editor Regarding "Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42435130},
issn = {2193-8245},
}

@article {pmid42435540,
year = {2026},
author = {Jaber, B and Abd, MA and Younis, SMD and Rizaev, J and Salih, RM and Jaber, MA and Kholboyev, N and Farajipour, H},
title = {Retinal organoids and stem cell therapy for vision restoration: current progress, persistent challenges, and future directions.},
journal = {International immunopharmacology},
volume = {186},
number = {},
pages = {117120},
doi = {10.1016/j.intimp.2026.117120},
pmid = {42435540},
issn = {1878-1705},
abstract = {Vision restoration is a vital yet challenging objective in ophthalmology, as traditional therapies cannot reverse irreversible retinal damage. This issue is of significant concern, considering that millions globally are afflicted by untreatable degenerative conditions such as retinitis pigmentosa (RP) and age-related macular degeneration. Stem cell treatments and retinal organoid (RO) technology have emerged as revolutionary methodologies. ROs derived from pluripotent stem cells (PSCs) autonomously form three-dimensional (3D) laminar structures that mimic the natural human retina, providing exceptional platforms for disease modeling, pharmacological screening, and cellular replacement. Clinical studies indicate that retinal pigment epithelium (RPE) transplantation enhances visual function. In contrast, PSC-derived mesenchymal stem cells (MSCs), retinal progenitor cells (RPCs), and RPE grafts have neuroprotective and regenerative capabilities in preclinical and early-phase trials. Notwithstanding this advancement, several challenges remain, including suboptimal cell survival, insufficient functional synaptic integration, immunological rejection, tumorigenic potential, and the absence of standardized production processes. This article presents three unique contributions, diverging from previous reviews that focus solely on positive outcomes: (1) a comprehensive assessment of advancements and challenges in PSCs, MSCs, RPCs, and RPE; (2) a methodical examination of the disparity between structural engraftment and genuine functional integration; and (3) a cohesive discourse on innovative strategies such as optogenetics, 3D bioprinting, and extracellular vesicle-based therapies. We consolidate recent clinical discoveries, highlight persistent obstacles, and provide a roadmap for the future. Growing evidence suggests that, despite significant obstacles, effective retinal regeneration is gradually becoming a reality.},
}

@article {pmid42433372,
year = {2026},
author = {Schlecht, A and Müllerbauer, L and Fitz, K and Brunne, B and Hofmann, N and Müller, C and Hillenkamp, J and Ergün, S and Neueder, A and Braunger, BM},
title = {Endothelial TGFβ signaling modulates choroidal neovascularization severity via myeloid-endothelial cell interaction.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1813788},
pmid = {42433372},
issn = {1664-3224},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/etiology ; *Signal Transduction ; Mice ; *Transforming Growth Factor beta/metabolism ; *Endothelial Cells/metabolism ; Receptor, Transforming Growth Factor-beta Type II/genetics/metabolism ; Disease Models, Animal ; Mice, Knockout ; *Myeloid Cells/metabolism ; *Cell Communication ; Microglia/metabolism ; Blood-Retinal Barrier/metabolism ; Fibrinogen/metabolism/genetics ; Mice, Inbred C57BL ; },
abstract = {INTRODUCTION: The blood-retinal barrier (BRB) is essential for maintaining retinal homeostasis, consequently its disruption contributes to pathological angiogenesis in diseases such as neovascular age-related macular degeneration (nAMD). Choroidal neovascularization (CNV) is considered as a hallmark of nAMD. These newly formed vessels break through the BRB leading to rapid and severe vision loss. Here, we investigated how endothelial TGFβ signaling interacts with mononuclear phagocytes (MP), such as microglia to regulate choroidal neovascularization (CNV).

METHODS: In this study, we used a laser-induced CNV model in mice with endothelial-specific Tgfbr2 deletion and concomitant MP depletion via PLX5622.

RESULTS: We demonstrate that loss of endothelial TGFβ signaling significantly exacerbates CNV. Strikingly, this effect is fully rescued by MP depletion. Transcriptome and RNA localization of CNV lesions identified fibrinogen alpha chain (Fga) as a MP-derived factor that is exclusively upregulated in mice without endothelial TGFβ signaling.

DISCUSSION: These findings suggest a novel TGFβ-dependent interaction between endothelial cells and MP that promotes angiogenesis through microglia derived Fga expression.},
}

Animals
*Choroidal Neovascularization/metabolism/pathology/etiology
*Signal Transduction
Mice
*Transforming Growth Factor beta/metabolism
*Endothelial Cells/metabolism
Receptor, Transforming Growth Factor-beta Type II/genetics/metabolism
Disease Models, Animal
Mice, Knockout
*Myeloid Cells/metabolism
*Cell Communication
Microglia/metabolism
Blood-Retinal Barrier/metabolism
Fibrinogen/metabolism/genetics
Mice, Inbred C57BL

@article {pmid42434188,
year = {2026},
author = {Ruiz-Medrano, J and Puertas, M and Hinojosa-Gonzalez, M and Moreno-Alboran, C and Ruiz-Moreno, JM},
title = {Pharmacoeconomic analysis of switch to faricimab for neovascular age-related macular degeneration in real clinical practice.},
journal = {Global & regional health technology assessment},
volume = {13},
number = {},
pages = {185-191},
pmid = {42434188},
issn = {2283-5733},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is one of the leading causes of severe vision loss among older adults. This condition impairs patients' quality of life and imposes a significant economic burden on the healthcare system. This study aims to determine the difference in direct healthcare cost (DHC) after switching the current pharmacological treatment in patients with nAMD, under a treat-and-extend regimen, to faricimab.

METHODS: Treatment interval data obtained after switching to faricimab in 225 eyes with nAMD was used to calculate total DHC in comparison with the theoretical DHC had if patients remained on their previous treatment (drug and treatment interval). An "optimal responder" was defined as a patient whose interval between intravital injections was extended by more than 8 weeks relative to the baseline treatment interval.

RESULTS: The theoretical DHC of treatment for this series of nAMD eyes would have been €2,351,241.90, compared with an actual DHC after switching to faricimab of €1,718,015.83, representing a saving of €633,226.06 for 225 eyes. The mean theoretical DHC would have been €10,449.96 ± 4,340.18 (from 1,423.75 to 23,695.20), compared with a mean actual total cost of €7,635.62 ± 2,465.07 (from 2,571.88 to 15,431.28). The mean actual DHC was €8,499.74 ± 2,678.42 in the "non-optimal responder" group versus €6,593.59 ± 1,674.91 in the "optimal responder" group (p < 0.001).

CONCLUSION: Switching to faricimab in patients with nAMD on a treat-and-extend regimen with a treatment interval of less than 12 weeks resulted in a significant reduction in total DHC, particularly in the "optimal responder" group.},
}

@article {pmid42434330,
year = {2026},
author = {Qin, Z and Liu, Y and Yin, YU and Ding, J and Zhang, H and Li, A and Campbell, D and Wu, X and Zou, KE and Keenan, TDL and Chew, EY and Lu, Z and Tham, YC and Liu, N and Zhang, X and Chen, Q},
title = {LMOD+: A Comprehensive Multimodal Dataset and Benchmark for Developing and Evaluating Multimodal Large Language Models in Ophthalmology.},
journal = {ACM transactions on computing for healthcare},
volume = {7},
number = {3},
pages = {},
pmid = {42434330},
issn = {2637-8051},
abstract = {The rising prevalence of vision-threatening eye diseases poses a major global health and economic burden, yet timely diagnosis remains limited by workforce shortages, diagnostic delays, and restricted access to specialized care. Artificial intelligence (AI) offers potential solutions. In particular, recent progress in foundation models and large language models-especially multimodal large language models (MLLMs)-has shown promise in medical image interpretation and automated clinical documentation. However, advancing MLLMs for ophthalmology is hindered by the lack of unified, comprehensive benchmark datasets for development and evaluation. Most existing benchmarks were designed for earlier models, which focused on narrow tasks or specific disease conditions. These benchmarks typically provide outputs in the form of disease labels rather than free-text responses. As a result, they are less suitable for assessing emerging generative models. In this work, we present LMOD+, a large-scale multimodal ophthalmology benchmark dataset comprising 32,633 instances with multi-granular annotations across 12 common ophthalmic conditions and 5 imaging modalities. The dataset integrates imaging, anatomical structures, demographics, and free-text annotations. It supports primary ophthalmic applications such as anatomical structure recognition, disease screening, disease staging, and demographic prediction for potential performance bias evaluation. Alongside the dataset, we introduce a systematic and unified data curation pipeline that repurposes existing or new datasets for MLLM development. LMOD+ extends our preliminary LMOD benchmark-the first multimodal ophthalmology benchmark for MLLMs-with three major enhancements. First, we expanded the dataset by nearly 50% (from 21,933 to 32,633 instances). The color fundus photography (CFP) modality, the most accessible imaging modality in ophthalmology, was significantly enlarged to cover a broader range of pathological conditions. Second, we broadened task coverage to include (a) 12 binary disease diagnosis tasks for prevalent conditions such as diabetic retinopathy, age-related macular degeneration, and retinal vein occlusion; (b) multi-class ophthalmic disease diagnosis; (c) disease severity classification, including a diabetic retinopathy staging task, which uses two internationally adopted grading standards: the international clinical diabetic retinopathy classification and the Scottish diabetic retinopathy grading scheme classification; and (d) demographic prediction (age and sex) to assess potential model bias. Third, we systematically evaluated 24 state-of-the-art MLLMs, including recent models from the InternVL, Qwen, and DeepSeek families. Our evaluations highlight both the promise and limitations of current MLLMs in ophthalmology. For example, Qwen-7B and InternVL achieved accuracies of 58.26% and 57.83% in disease screening under a zero-shot setting with a single model-a considerably more challenging paradigm than traditional fine-tuning, where separate models are trained for each specific task. InternVL also demonstrated potential in anatomical recognition. Nonetheless, overall performance remained suboptimal and often close to random baselines for challenging tasks such as disease staging, underscoring the substantial gap between general-domain MLLMs and the specialized requirements of ophthalmology. We publicly release the dataset, curation pipeline, and leaderboard to encourage community-wide development and evaluation of MLLMs, with the goal of advancing ophthalmic applications and ultimately reducing the global burden of vision-threatening diseases through AI. The dataset website, benchmark leaderboard, and download link are available at https://kfzyqin.github.io/lmod_plus.},
}

@article {pmid42435129,
year = {2026},
author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, N},
title = {A Response to: Letter to the Editor Regarding "Aflibercept 8 mg Versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42435129},
issn = {2193-8245},
support = {P30-EY026877//Prevent Blindness/ ; },
}

@article {pmid42410910,
year = {2026},
author = {Ji, Y and Sun, Y and Huang, X and Liang, J and Fang, D and Yang, W and Feng, L and Zhang, S},
title = {Targeting the SNAI1-LAMP3 axis to restore lysosomal function and alleviate autophagic flux impairment to delay retinal degeneration.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-21},
doi = {10.1080/15548627.2026.2700025},
pmid = {42410910},
issn = {1554-8635},
abstract = {Retinal degenerative diseases are a leading cause of irreversible blindness. Their pathogenesis is intricately linked to oxidative stress-induced dysfunction of retinal pigment epithelial (RPE) cells and subsequent retinal degeneration. Macroautophagy/autophagy, a critical cellular degradation pathway, plays a vital role in maintaining RPE homeostasis, yet its dysregulation in retinal degenerative diseases remains poorly understood. In this study, we observed that sodium iodate (NaIO3), an oxidative stress inducer, triggered lysosomal dysfunction via lysosomal membrane permeabilization (LMP), thereby impairing autophagic flux in RPE cells and exacerbating retinal degeneration. RNA sequencing identified LAMP3 (lysosomal-associated membrane protein 3) as a downregulated gene following NaIO3 treatment. Functionally, LAMP3 overexpression alleviated NaIO3-induced LMP, improved lysosomal function, and alleviated autophagic impairment. Furthermore, upregulation of LAMP3 reduced oxidative stress and apoptosis in RPE cells, while alleviating retinal degeneration in a NaIO3-induced mouse model. Mechanistically, our data suggested that NaIO3 upregulated the transcription factor SNAI1, which acts as a transcriptional repressor of LAMP3. SNAI1 knockdown increased LAMP3 expression, thereby facilitating the recovery of lysosomal function and the alleviation of autophagic impairment. Collectively, our findings indicate that the SNAI1-LAMP3 axis contributes to the regulation of the autophagy-lysosomal pathway in retinal degeneration, highlighting a potential therapeutic target for delaying disease progression.Abbreviations: AMD: age-related macular degeneration; AO: acridine orange; Baf A1: bafilomycin A1; BAX: BCL2-associated X protein; BCL2: B cell leukemia/lymphoma 2; BSA: bovine serum albumin; CCK-8: cell counting kit-8; ChIP: chromatin immunoprecipitation; CM-H2DCFDA: chloromethyl-2',7'-dichlorodihydrofluorescein diacetate; CTSD: cathepsin D; DAPI: 4',6-diamidino-2-phenylindole; DEGs: differentially expressed genes; DHE: dihydroethidium; EdU: 5-ethynyl-2'-deoxyuridine; ERG: electroretinography; GSEA: gene set enrichment analysis; H&E: hematoxylin and eosin; HsRPE: human primary retinal pigment epithelial; JC-1: 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide; LAMP1: lysosomal-associated membrane protein 1; LAMP2: lysosomal-associated membrane protein 2; LAMP3: lysosomal-associated membrane protein 3; LGALS3: lectin, galactose binding, soluble 3; LLOMe: leu-leu methyl ester; LMP: lysosomal membrane permeabilization; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MMP: mitochondrial membrane potential; NAC: N-acetyl-L-cysteine; NaIO3 : sodium iodte; NC: negative control; OCT: optical coherence tomography; PCA: principal component analysis; PI: propidium iodide; qRT-PCR: quantitative real-time polymerase chain reaction; Rapa: rapamycin; ROS: reactive oxygen species; RP: retinitis pigmentosa; RPE: retinal pigment epithelium; RPE65: retinal pigment epithelium 65; siRNA: small interfering RNA; SNAI1: snail family zinc finger 1; SQSTM1/p62: sequestosome 1; TJP1/ZO-1: tight junction protein 1; ZNF135: zinc finger protein 135.},
}

@article {pmid42423410,
year = {2026},
author = {Quarta, A and Huang, J and Abbasgholizadeh, R and Soylu, C and Chujo, S and Alhelaly, M and Velaga, SB and Nittala, MG and Corradetti, G and Ip, M and Mastropasqua, R and Sadda, SR},
title = {Clinical and Imaging Characteristics of Thin and Thick Idiopathic Epiretinal Membranes Assessed by High-Resolution OCT.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {8},
pages = {28},
doi = {10.1167/iovs.67.8.28},
pmid = {42423410},
issn = {1552-5783},
mesh = {Humans ; *Epiretinal Membrane/diagnosis/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Female ; Male ; Aged ; Visual Acuity ; Aged, 80 and over ; Retrospective Studies ; Prevalence ; },
abstract = {PURPOSE: The purpose of this study was to determine the prevalence and imaging characteristics of thin and thick idiopathic epiretinal membranes (ERMs) using high-resolution (HR) optical coherence tomography (OCT) and to identify clinical factors associated with ERM thickness phenotype.

METHODS: All patients underwent comprehensive ophthalmologic examination and multimodal imaging, including HR-OCT. ERM morphology was evaluated on fovea-centered OCT scans and classified as thin or thick based on preretinal reflectivity patterns. Multivariable generalized estimating equations (GEEs) were used to identify factors independently associated with ERM type while accounting for inter-eye correlation.

RESULTS: Fifty-four eyes included in this analysis and 28 (51.9%) were classified as thin ERM, whereas 26 (48.1%) were thick ERM. Patients with thick ERM were significantly older than those with thin ERM (81.6 ± 6.2 vs. 75.7 ± 10.8 years, P = 0.039). Pseudophakia was more prevalent in the thick ERM group (84.6% vs. 60.7%, P < 0.001), as was the presence of AMD (69.2% vs. 28.6%, P = 0.003). Mean central macular thickness (CMT) and best-corrected visual acuity (BCVA) did not differ significantly between thin and thick ERM groups (P > 0.05). In multivariable analysis, pseudophakia (odds ratio [OR] = 10.33, 95% confidence interval [CI] = 1.29-83.10, P = 0.028) and age-related macular degeneration (AMD; OR = 4.12, 95% CI = 1.01-16.87, P = 0.049) were independently associated with thick ERM.

CONCLUSIONS: HR-OCT enables in vivo differentiation of thin and thick idiopathic ERMs. Thick ERM is independently associated with pseudophakia and AMD but not with greater CMT or worse BCVA, suggesting that ERM thickness phenotype may reflect differences in factors other than vitreoretinal interface biology alone.},
}

Humans
*Epiretinal Membrane/diagnosis/pathology/diagnostic imaging
*Tomography, Optical Coherence/methods
Female
Male
Aged
Visual Acuity
Aged, 80 and over
Retrospective Studies
Prevalence

@article {pmid42424405,
year = {2026},
author = {Osba, AA and Saleh, F and Verma, AV and Mihalache, A and El Aziz Hendy, A and Osba, RA and Mishra, AV and Kertes, PJ and Kohly, RP and Muni, RH and Popovic, M},
title = {Post-Marketing Ocular Adverse Events Associated with Tamoxifen and Raloxifene: A Population-Based Pharmacovigilance Study.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004916},
pmid = {42424405},
issn = {1539-2864},
abstract = {PURPOSE: Tamoxifen and raloxifene are selective estrogen receptor modulators used for breast cancer treatment, and osteoporosis prevention. While systemic adverse events (AEs) are well recognized, ocular AEs have been less comprehensively characterized. The purpose of this study was to evaluate postmarketing ocular AEs associated with tamoxifen and raloxifene using a pharmacovigilance database.

METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) data from Q4 2003 to Q2 2025 were analyzed using OpenVigil 2.1. Disproportionality analyses were conducted to calculate reporting odds ratios (RORs) for drug-AE pairs compared with all other drugs.

RESULTS: There were a total of 4,084 reports of AEs associated with tamoxifen (mean age 56.7 years), including 505 ocular AEs. The strongest signals were for corneal graft rejection (ROR 118.9), retrobulbar hemorrhage (104.6), ophthalmic vein thrombosis (82.7), retinal deposits (80.7), and macular hole (78.6). Additional events included maculopathy, retinopathy, and optic neuropathy. There were 5,600 reports of AEs associated with raloxifene (mean age 68.6 years), including 437 ocular AEs. The most prominent signals were vascular, including retinal vein thrombosis (ROR 340.0), retinal vascular thrombosis (133.8), retinal artery thrombosis (54.9), and retinal vein occlusion (42.9). Other events included reduced visual acuity, cataract, macular degeneration, and glaucoma.

CONCLUSIONS: Tamoxifen and raloxifene had unique ocular AE profiles. Tamoxifen was primarily linked to retinal, optic nerve, and corneal disorders, whereas raloxifene was strongly associated with retinal vascular and thromboembolic events. These findings underscore the importance of clinician awareness and future prospective studies to further elucidate the risks.},
}

@article {pmid42424532,
year = {2026},
author = {Wu, HC and Gu, A and Chang, YL and Lu, CK and Lee, YC and Yu, PW and Lee, TH},
title = {Utilize Metabolomics Molecular Networking to Guide the Discovery of Chemical Entities from Cordyceps militaris Against Blue Light Hazards.},
journal = {Journal of natural products},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jnatprod.6c00427},
pmid = {42424532},
issn = {1520-6025},
abstract = {Increasing exposure to blue light has raised concern about retinal injury, particularly in retinal pigment epithelial (RPE) cells. N-retinylidene-N-retinylethanolamine (A2E), a photosensitive fluorophore associated with age-related macular degeneration, is an important mediator of this process. In this study, feature-based molecular networking guided the identification of cordylutenes A-J (1-10), a new molecular family of blue light-protective fungal pigments from Cordyceps militaris. These metabolites possess a previously unreported symmetric all-E C20 polyene dicarbonyl skeleton with carotenoid-like UV absorption. They were characterized at the molecular-family level by shared UV features and diagnostic, internally consistent MS[2] fragmentation patterns. Cordylutenes A (1) and B (2) were isolated as representative members for structural characterization. In an A2E-mediated blue-light injury model in ARPE-19 cells, the cordylutene complex (CCL, 1 μg/mL) and cordylutene A (1, 0.1 μg/mL) improved cell viability to 84.78 ± 4.02% and 92.14 ± 1.88%, respectively, and reduced intracellular oxidative stress to 63.67 ± 3.33% and 43.89 ± 9.59%, respectively. These findings identify cordylutenes as a new family of fungal pigments with protective effects in an A2E-mediated photo-oxidative retinal cell injury model.},
}

@article {pmid42425278,
year = {2026},
author = {Badla, O and Shen, M and El-Mulki, OS and Berni, A and Kumar, BS and Herrera, G and Beqiri, S and Lam, W and Herrera, E and Moxam, J and Trivizki, O and O'Brien, R and Waheed, NK and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Comparing Eye-Level and Site-Specific High-Risk OCT Biomarkers Preceding the Onset of Large Hypertransmission Defects.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.07.002},
pmid = {42425278},
issn = {1879-1891},
abstract = {PURPOSE: To compare the site-specific optical coherence tomography (OCT) biomarkers that appear prior to the formation of large hypertransmission defects (hyperTDs) with the eye-level OCT biomarkers that were shown to predict disease progression in eyes with intermediate AMD (iAMD).

DESIGN: Retrospective subgroup analysis of a prospective cohort study.

METHODS: A prospectively enrolled cohort of eyes with iAMD, imaged with swept-source OCT (SS-OCT), was retrospectively reviewed to identify eyes that developed large hyperTDs. Large hyperTDs were defined as bright lesions with a greatest linear dimension (GLD) of ≥250 μm on an en face sub-retinal pigment epithelium (RPE) slab image created using segmentation boundaries positioned 64-400 μm below Bruch's membrane (BM). All visits prior to the formation of the large hyperTDs were retrospectively reviewed to identify the OCT biomarker at the retinal location where the initial large hyperTD formed.

RESULTS: 82 of 171 eyes (48%) with iAMD developed at least one large hyperTD. At the first visits when the large hyperTD developed, a total of 119 large hyperTDs were detected. Hyperreflective foci (HRF) were the most frequent OCT biomarker at the sites prior to the formation of hyperTDs (88/119, 74%). Soft drusenoid lesions were the second-most frequent biomarker (77/119, 65%); however, 67 of these lesions occurred in conjunction with HRF. Calcified drusen (CaD) were present at 19 of 119 sites (16%). Of these 19 CaD lesions, 7 contained hyporeflective cores (hypoRC-CaD), and 11 were associated with HRF. Non-calcified hyporeflective core drusen (hypoRCD) were present at 16/119 (13%) sites, with three of the hypoRCD associated with HRF. Basal laminar deposits (BLamD) were present at 2 of 119 sites (2%), both of which were associated with HRF. Single cases of a vitelliform lesion and a small hyperTD were also identified prior to the large hyperTDs.

CONCLUSIONS: Site-specific analysis showed that HRF were the most frequent OCT biomarker at the sites prior to the formation of large hyperTDs. Soft drusenoid lesions and HRF were frequently observed together, consistent with our previous eye-level multivariable analysis, which showed that drusen volume was not independently predictive of the future formation of large hyperTDs.},
}

@article {pmid42425279,
year = {2026},
author = {El-Mulki, OS and Badla, O and Kumar, BS and Berni, A and Shen, M and Kastner, J and Beqiri, S and Herrera, G and Lam, W and Herrera, E and Trivizki, O and Le, VH and Nicola, MD and O'Brien, R and Waheed, NK and Gregori, G and Wang, RK and Rosenfeld, PJ},
title = {Detection of Hyporeflective Core Drusen and the Onset of Large Choroidal Hypertransmission Defects in Intermediate AMD.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.07.001},
pmid = {42425279},
issn = {1879-1891},
abstract = {PURPOSE: To investigate the association between hyporeflective core drusen (hypoRCD) and the formation of large choroidal hypertransmission defects (hyperTDs) in eyes with intermediate age-related macular degeneration (iAMD), we used swept-source optical coherence tomography (SS-OCT) imaging and a novel algorithm to detect and quantify hypoRCD before the onset of hyperTDs.

DESIGN: Post hoc subgroup analysis of a prospective cohort study.

METHODS: Eyes with iAMD enrolled in a prospective SS-OCT imaging study were retrospectively reviewed. SS-OCT angiography (SS-OCTA) scans were obtained at baseline and follow-up. En face images derived from a retinal pigment epithelium (RPE) to Bruch's membrane (BM) slab identified hyporeflective cores within drusen as dark spots. A sub-RPE slab located 64-400 μm beneath BM was used to identify calcified drusen (CaD) based on their characteristic choroidal hypotransmission defects (hypoTDs). Hyporeflective cores associated with CaD (hypoRC-CaD) were identified. Hyporeflective cores not associated with calcified drusen were labeled as non-calcified hypoRCD and quantified separately. Large hyperTDs, defined as bright lesions with a greatest linear dimension (GLD) ≥250 μm on the sub-RPE slab, were graded. A semi-automated algorithm measured the areas of hypoRC-CaD and non-calcified hypoRCD within a 5 mm circle centered on the fovea, and their association with hyperTD formation was analyzed. The risk attributed to CaD with and without hyporeflective cores was evaluated.

RESULTS: The study included 171 eyes from 121 patients with a median follow-up of 59.1 months (95% CI: 52.0-67.8). Eighty-two eyes developed at least one large hyperTD during follow-up. The total hypoRCD area at the time of hyperTD onset was 0.026 mm² (range: 0-0.349 mm²), compared to 0.015 mm² (range: 0-0.532 mm²) at the final visit in eyes that did not develop hyperTDs. When drusen volume, hyperreflective foci (HRF) area, CaD area, and total hypoRCD area were studied as risk factors, the hypoRCD area was not a significant predictor of hyperTD onset in the univariable (P = 0.36) or multivariable (P = 0.60) Cox regression models.

CONCLUSIONS: HypoRCD alone were not predictive of progression to atrophy, but the risk of progression was found to be associated with CaD with or without hyporeflective cores.},
}

@article {pmid42426273,
year = {2026},
author = {Schmidt, R and Weissenbacher, LM and Vécsei-Marlovits, V and Weingessel, B},
title = {Comparison of intravitreal anti-VEGF treatment burden in different retinal diseases.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42426273},
issn = {1476-5454},
abstract = {BACKGROUND/OBJECTIVES: To compare the subjective treatment burden of intravitreal anti-VEGF therapy (IVT) among patients with neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME), and macular oedema secondary to retinal vein occlusion (CME).

SUBJECTS/METHODS: This single-centre, cross-sectional study surveyed 393 patients at the Department of Ophthalmology, Hietzing Hospital, Vienna. All participants had received at least five anti-VEGF intravitreal injections and had been in treatment for at least six months. Data were collected via a structured questionnaire, assessing perceived treatment burden, sociodemographics, and treatment-related experiences. Statistical analysis was performed using SPSS, with nonparametric tests applied due to ordinal data.

RESULTS: Of the 393 participants (nAMD: 305; CME: 55; DME: 33), 64% reported no or only slight burden from treatment frequency or injections. There was no statistically significant difference in overall treatment burden between disease groups (p > 0.4). However, the nature of the burden differed: nAMD patients most often cited fear of progressive vision loss, while CME and DME patients more frequently named the injection itself as the greatest burden. Better patient education significantly correlated with a lower perceived burden (p < 0.001). Nearly half of the patients required assistance with clinic visits.

CONCLUSIONS: Although the overall perceived burden of anti-VEGF treatment was similar across retinal diseases, patients' specific concerns varied. Addressing these differences through personalised education and communication may help alleviate treatment-related anxiety and improve adherence. These findings highlight the importance of tailoring support strategies to individual patient experiences within long-term intravitreal treatment regimens.},
}

@article {pmid42431462,
year = {2026},
author = {Cozzi, M and Zweifel, SA and Spooner, K and Romano, F and Guymer, R and Sadda, SR and Staurenghi, G and Invernizzi, A},
title = {Non-advanced age-related macular degeneration: current concepts and future perspectives.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100346},
doi = {10.1016/j.apjo.2026.100346},
pmid = {42431462},
issn = {2162-0989},
abstract = {Non-advanced age-related macular degeneration (AMD), encompassing early and intermediate stages, represents a critical therapeutic window before irreversible central vision loss. Traditionally defined by drusen size and pigmentary abnormalities on color fundus photography, disease characterization has evolved substantially with the integration of multimodal imaging biomarkers. Contemporary imaging enables detailed structural phenotyping, including reticular pseudodrusen (also known as subretinal drusenoid deposits), hyperreflective foci, and incomplete retinal pigment epithelium and outer retinal atrophy, which refine risk stratification and provide insight into progression toward advanced disease. Functional assessment has expanded beyond best-corrected visual acuity to include low-luminance visual acuity, contrast sensitivity, dark adaptation, and microperimetry, many of which are more sensitive to early dysfunction. However, standardization and regulatory approval of these endpoints remain ongoing challenges. Non-advanced AMD arises from complex interactions among genetic susceptibility, aging, environmental exposures, and systemic metabolic factors. Smoking remains the strongest modifiable risk factor, while Mediterranean dietary patterns appear protective. Currently, no pharmacologic therapies are approved for non-advanced AMD. The Age-Related Eye Disease Study formulations remain the only interventions proven to reduce progression in high-risk individuals. Emerging approaches, including subthreshold laser therapy and photobiomodulation, show preliminary promise but require validation in robust and adequately powered randomized clinical trials. Recent consensus efforts emphasize biomarker-driven classification and highlight the heterogeneity of AMD phenotypes across populations. Future research priorities include validation of quantitative imaging and functional endpoints, integration of artificial intelligence-based predictive models, and development of targeted therapies to delay progression. These endevours will be essential to advance precision prevention strategies.},
}

@article {pmid42431855,
year = {2026},
author = {Litvin, DG and Boizot, A and Corna, A and Navarro, A and Keller, J and Heuschkel, MO and Roux, A and Zeck, G and Tran, HV and Ghezzi, D},
title = {Resting-state electroretinography reveals pathological retinal oscillations in retinitis pigmentosa mice and patients.},
journal = {Nature communications},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41467-026-75520-9},
pmid = {42431855},
issn = {2041-1723},
abstract = {Retinal remodeling occurs in both retinitis pigmentosa and age-related macular degeneration. However, it is still unknown whether spared retinal circuits are also functionally altered. Functional changes have been observed in animal models of retinitis pigmentosa, including the emergence of bursting oscillatory activity in retinal ganglion cells. Yet, comparable oscillatory activity, or other functional alterations, has not been demonstrated in patients. To address this gap, here we report a non-invasive corneal neurotechnology measuring in-vivo resting-state electroretinography and analyzing its frequency content and temporal characteristics to identify biomarkers of functional remodeling. We document that retinal remodeling induces bursting oscillatory activity in-vivo in retinitis pigmentosa mouse models and translate these results to patients. Moreover, we showed in mice that bursting oscillatory activity can be pharmacologically modulated in-vivo. Furthermore, reducing this oscillatory activity increases retinal excitability to electrical stimulation. These results are crucial for a better understanding of retinal degeneration and contribute to sight restoration efforts.},
}

@article {pmid42433200,
year = {2026},
author = {Karuntu, JS and Nguyen, XT and Talib, M and van Schooneveld, MJ and Wijnholds, J and van Genderen, MM and Twisk, J and Schalij-Delfos, NE and Klaver, CCW and Florijn, RJ and Ten Brink, JB and Smoor, MA and van den Born, LI and Hoyng, CB and Thiadens, AAHJ and Boon, CJF},
title = {CRB1-Associated Inherited Retinal Dystrophies: Prospective Natural History Study With 4 Years of Follow-Up.},
journal = {Clinical & experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70142},
pmid = {42433200},
issn = {1442-9071},
support = {//Algemene Nederlandse Vereniging ter voorkoming van Blindheid/ ; //Landelijke Stichting voor Blinden en Slechtzienden/ ; //Oogfonds/ ; //Curing Retinal Blindness Foundation/ ; //Stichting Retina Fonds/ ; //Bontius Stichting/ ; //Stichting Blindenhulp/ ; },
abstract = {BACKGROUND: The lack of validated and sensitive clinical endpoints remains a major challenge in the design of gene therapy trials for inherited retinal dystrophies (IRDs). This prospective longitudinal cohort study describes the natural disease progression of IRDs caused by pathogenic mutations in the Crumbs homologue 1 (CRB1) gene, and identifies sensitive clinical endpoints.

METHODS: In this single-centre study, patients with genetically confirmed CRB1-associated IRD were assessed at baseline, 2-year and 4-year follow-up. The phenotyping protocol included best-corrected visual acuity (BCVA), Goldmann perimetry, mesopic microperimetry, full-field stimulus testing (FST), ophthalmoscopy and assessment of retinal structural integrity on spectral-domain optical coherence tomography and fundus autofluorescence.

RESULTS: Twenty of the 22 enrolled patients completed the 4-year follow-up, including patients with retinitis pigmentosa (n = 17), cone-rod dystrophy (n = 2) or macular dystrophy (n = 1). Significant decreases were observed for BCVA (-6.2 ETDRS letters, 95% confidence interval [CI] -10.1 to -2.3; p = 0.003), V4e isopter seeing retinal area (-43.9 mm[2], 95% CI, -72.3 to -15.5; p = 0.003) and mean sensitivity on microperimetry (-2.5 dB, 95% CI, -3.3 to -1.6; p < 0.001). FST thresholds for white, blue and red stimuli did not significantly change over 4 years (p = 0.24; p = 0.78; p = 0.60, respectively). The continuity of the ellipsoid zone (EZ) and the external limiting membrane (ELM) on SD-OCT were increasingly disrupted in six patients over the course of this study.

CONCLUSION: Except for FST responses, a significant decrease was observed over 4 years in the visual function parameters of BCVA, Goldmann perimetry and microperimetry and these may thus be used as sensitive clinical endpoints.},
}

@article {pmid42411867,
year = {2026},
author = {Curcio, CA and Gao, L and Pu, J and Gooden, L and Thomas, TN and Kim, SS and Goerdt, L and Berlin, A and McGwin, G and Sloan, KR and Johnson, EJ and Owsley, C},
title = {Xanthophyll Carotenoid Intake, Plasma Levels, and Retinal Visualization in Aging and Age-Related Macular Degeneration: ALSTAR2.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {8},
pages = {22},
doi = {10.1167/iovs.67.8.22},
pmid = {42411867},
issn = {1552-5783},
mesh = {Humans ; Female ; *Macular Degeneration/blood/diagnosis ; Aged ; Cross-Sectional Studies ; Male ; *Aging/physiology ; *Lutein/administration & dosage/blood ; *Zeaxanthins/administration & dosage/blood ; *Xanthophylls/administration & dosage/blood ; Dietary Supplements ; Middle Aged ; Aged, 80 and over ; *Retina/diagnostic imaging/pathology ; Fluorescein Angiography/methods ; Macular Pigment ; Tomography, Optical Coherence/methods ; },
abstract = {PURPOSE: The purpose of this study was to determine cross-sectional associations among intake of xanthophyll carotenoids lutein and zeaxanthin (L&Z), plasma L&Z, and two wavelength autofluorescence (2WAF) retinal imaging in aging and age-related macular degeneration (AMD).

METHODS: Adults ≥63 years old from a comprehensive ophthalmology clinic underwent assessments: macular health (Age-Related Eye Disease Study [AREDS] 9-step); self-reported L&Z intake from diet (LZQ Food Frequency Questionnaire) and supplements; total intake; macular pigment optical volume (MPOV; in 2WAF); non-fasting plasma L&Z; and HDL and LDL cholesterol. Associations were adjusted for age and HDL/LDL.

RESULTS: We studied 369 persons (74 ± 5.8 years, 60% women, 89% White, 62% never-smoker, and 23% supplement use) and 369 eyes (48.4% healthy, 26.0% early AMD [eAMD], and 25.2% intermediate AMD [iAMD]). Diagnostic groups differed in supplement users (10%, 17%, and 56%), total L&Z intake (5.3 ± 6.4, 5.5 ± 5.4, and 11.0 ± 8.3 mg/d, P < 0.01), and MPOV (1.04 ± 0.46, 1.02 ± 0.52, and 1.33 ± 0.61). Groups did not differ in dietary intake (3.8 ± 4.5, 3.4 ± 3.2, and 3.7 ± 3.8 mg/d), plasma HDL, or HDL/LDL. Associations were strong between plasma L&Z and MPOV (r = 0.41-0.67, P < 0.01); moderate between total intake and plasma L&Z (Spearman r = 0.29-0.50, P < 0.01); weaker but significant for L&Z intake, and MPOV (r = 0.22-0.30, P < 0.01) of 3-mm-diameter macula lutea only, for eAMD and iAMD.

CONCLUSIONS: In a large US sample, we assess for the first time L&Z intake from diet and supplements and determined the relative strength of correlations among intake, plasma, and retinal xanthophylls. We replicate our earlier finding of elevated retinal and plasma L&Z in iAMD. LZQ and 2WAF are suitable outcome measures for future interventions that directly test the impact of L&Z on AMD onset and progression.},
}

Humans
Female
*Macular Degeneration/blood/diagnosis
Aged
Cross-Sectional Studies
Male
*Aging/physiology
*Lutein/administration & dosage/blood
*Zeaxanthins/administration & dosage/blood
*Xanthophylls/administration & dosage/blood
Dietary Supplements
Middle Aged
Aged, 80 and over
*Retina/diagnostic imaging/pathology
Fluorescein Angiography/methods
Macular Pigment
Tomography, Optical Coherence/methods

@article {pmid42414674,
year = {2026},
author = {Beazley-Long, N and Horder, JL and Green, KR and Bourne, JH and Lynch, AP and Ahmed, NS and Tabrizi, ZB and Diez-Pinel, G and Carroll, CP and Allen, CL and Cresswell, CT and Harris, PE and Ferreira, I and Mosqueira, D and Rayes, J and Mongan, NP and King, J and Denning, C and McIntyre, A and Stemmler, MP and Brabletz, S and Brabletz, T and Bates, DO and Benest, AV},
title = {Loss of endothelial ZEB1 enhances neovascularisation during choroidal neovascularisation.},
journal = {Communications biology},
volume = {},
number = {},
pages = {},
doi = {10.1038/s42003-026-10630-0},
pmid = {42414674},
issn = {2399-3642},
support = {PG/18/31/33759//British Heart Foundation (BHF)/ ; 223122/Z/21/Z//Wellcome Trust (Wellcome)/ ; },
abstract = {Choroidal neovascularisation (CNV) is a hallmark of wet/neovascular age-related macular degeneration (wAMD), characterized by aberrant blood vessel growth from the choroid into the retina. Both pathological angiogenesis and inflammation contribute to disease progression. Here we show that analsysis of single-cell RNA sequencing of experimental CNV lesions revealed upregulation of Zeb1 in angiogenic endothelial cells (ECs). We generated an endothelial-specific Zeb1 knockout (Zeb1[iECKO]) mouse model to assess its functional role. CNV was induced via laser photocoagulation, and vascular leakage and inflammation were evaluated using fluorescein angiography, immunohistochemistry, and transcriptomic analyses. Zeb1[iECKO] mice exhibited increased fluorescein leakage and enhanced vascular invasion during CNV, indicating destabilized neovascular structures. However, leukocyte infiltration within CNV lesions was not elevated. In vitro, ZEB1 knockdown in human ECs led to downregulation of inflammatory signalling pathways and reduced expression of adhesion molecules in response to TNF-α stimulation yet retained angiogenic capacity. ZEB1 coordinates angiogenic and inflammatory responses in CNV. Its loss enhances neovascularisation without promoting inflammation, suggesting a potential therapeutic target for modulating pathological angiogenesis in wAMD while minimizing inflammatory damage.},
}

@article {pmid42415636,
year = {2026},
author = {Chun, J and Choi, YJ and Kim, TY and Park, SI and Lee, SM and Choi, EY and Lee, J and Kim, M},
title = {Subretinal Tissue Plasminogen Activator Injection Using a Nanovitreoretinal Device for Massive Submacular Hemorrhage: A Retrospective Case Series.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2026.0084},
pmid = {42415636},
issn = {2092-9382},
abstract = {PURPOSE: To evaluate the efficacy of subretinal tissue plasminogen activator (tPA) injection in patients with massive submacular hemorrhage (SMH) with or without vitrectomy.

METHODS: This retrospective study included patients with massive SMH treated with subretinal tPA injection (12.5 μg/0.1 mL) using a nanovitreoretinal (NVR) device at a single tertiary referral center between 2020 and 2024. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central macular thickness (CMT); secondary outcomes included SMH thickness reduction and between-group comparison of surgical approaches.

RESULTS: 18 eyes of 15 patients (11 females, 61.1%) were analyzed. Twelve eyes underwent vitrectomy (66.7%), while six were treated without vitrectomy (33.3%). Baseline demographic and clinical characteristics were summarized descriptively because of the small and imbalanced subgroup sizes. Neovascular age-related macular degeneration was the leading etiology (17/18 eyes; 94.4%), comprising typical neovascular age-related macular degeneration (n=9, 50.0%), polypoidal choroidal vasculopathy (n=7, 38.9%), and retinal angiomatous proliferation (n=1, 5.6%); the remaining eye (5.6%) had peripheral exudative hemorrhagic chorioretinopathy. BCVA improved significantly from 1.79±0.77 to 1.28±0.83 logMAR (P=0.01), with 10 eyes (55.6%) achieving ≥3-line improvement. CMT decreased significantly at 6 months (673.8±346.7 to 266.0±327.1 μm; P=0.019), and 81.3% of eyes achieved ≥20% CMT reduction. SMH thickness decreased significantly post-injection (536.9±345.0 to 221.4±443.4 μm; P=0.02). No significant differences in final BCVA (1.24±0.77 vs. 1.37±1.01 logMAR; P=0.850) or CMT reduction rate (81.8% vs. 80.0%; P=0.999) were observed between vitrectomy and non-vitrectomy groups.

CONCLUSIONS: Subretinal tPA injection via the NVR device was associated with improvements in visual and anatomical outcomes in massive SMH. The non-vitrectomy approach showed no significant difference in outcomes compared with vitrectomy-assisted injection, but this exploratory finding should be interpreted cautiously given the small sample size.},
}

@article {pmid42419032,
year = {2026},
author = {Lee, SJ and Noh, SE and Kim, JH},
title = {Exogenous mitochondrial transplantation attenuates oxidative stress-driven retinal degeneration in a sodium iodate - induced mouse model.},
journal = {Neurobiology of aging},
volume = {168},
number = {},
pages = {1-13},
doi = {10.1016/j.neurobiolaging.2026.07.002},
pmid = {42419032},
issn = {1558-1497},
abstract = {Age-related macular degeneration (AMD) is a degenerative retinal disease initiated by dysfunction of the retinal pigment epithelium (RPE), in which age-related mitochondrial impairment, oxidative stress, chronic inflammation, and complement activation collectively drive outer retinal dysfunction and RPE atrophy, ultimately leading to progressive central vision loss. Accumulating evidence indicates that mitochondrial abnormalities, including excessive reactive oxygen species (ROS) production, mitochondrial fragmentation, and inflammatory signaling, play a central role in AMD pathogenesis. In this study, we investigated the therapeutic potential of exogenous mitochondrial transplantation using a sodium iodate (SI)-induced retinal degeneration model that recapitulates key pathological features of dry AMD. In ARPE-19 cells, SI-induced oxidative stress triggered mitochondrial fragmentation, inflammasome activation, and tight junction disruption, whereas delivery of mitochondria isolated from bone marrow-derived mesenchymal stem cells attenuated mitochondrial dysfunction and preserved RPE barrier integrity by suppressing oxidative and inflammatory signaling. Consistent with these in vitro findings, intravitreal mitochondrial transplantation in SI-treated mice attenuated RPE shedding/migration and outer nuclear layer disorganization while suppressing retinal oxidative stress, inflammatory cytokine expression, and complement activation. Importantly, mitochondrial transplantation mitigated the decline in retinal function, as assessed by electroretinography and optokinetic response testing, without fully restoring responses to control levels. Collectively, these results support exogenous mitochondrial transplantation as a promising cell-free therapeutic strategy to attenuate oxidative stress-driven retinal degeneration by modulating mitochondrial dysfunction and associated inflammatory pathways in AMD.},
}

@article {pmid42419444,
year = {2026},
author = {Li, FR and Peng, MJ and Lin, KQ and Zhou, Y and Yuan, FL and Jin, CY and Luo, H and Yu, L and Chi, W},
title = {Clonal Hematopoiesis of Indeterminate Potential and Genetic Susceptibility in Incident Age-Related Macular Degeneration: A Cohort Study.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.07.008},
pmid = {42419444},
issn = {1879-1891},
abstract = {PURPOSE: While inherited genetics strongly influence AMD risk, clonal hematopoiesis of indeterminate potential (CHIP), an age-related condition driven by somatic mutations and inflammation, is a novel, biologically plausible risk factor. Prospective evidence exploring their interplay with AMD incidence is lacking.

DESIGN: Prospective cohort study.

PARTICIPANTS: We conducted a prospective cohort study among 395,505 participants from the UK Biobank.

METHODS: CHIP was defined by somatic mutations (variant allele fraction ≥2%) in leukemia-associated driver genes from blood-derived exome sequencing. A polygenic risk score (PRS) for AMD was calculated using established genetic variants. We used Cox proportional hazards models to assess the independent and joint associations of CHIP and PRS with incident AMD.

MAIN OUTCOME MEASURES: Age-related macular degeneration.

RESULTS: During a median follow-up of 15.5 years, we documented 7,178 incident AMD cases. CHIP was associated with a 14% higher risk of incident AMD (HR: 1.14; 95% CI: 1.03, 1.26; P=0.009). Gene-specific analyses showed significant associations for mutations in DNMT3A (HR: 1.20; 95% CI: 1.06, 1.36; P=0.005), spliceosome genes (HR: 1.72; 95% CI: 1.02, 2.97; P=0.042), and DNA damage repair genes (HR: 1.68; 95% CI: 1.06, 2.67; P=0.028). A high AMD PRS was also associated with AMD risk. Participants with both any CHIP and a high PRS had a 3.26-fold higher risk (95% CI: 2.75, 3.86; P<0.001) compared to those with neither, with evidence of additive interaction (relative excess risk due to interaction [RERI] = 0.60; 95% CI: 0.07, 1.20). The joint effect was also strongest for DNMT3A mutation carriers with high PRS (HR: 3.69; 95% CI: 2.58, 3.96; P<0.001; RERI = 0.34; 95% CI: 0.04, 1.12). These synergistic effects were more pronounced in older adults.

CONCLUSION: CHIP was an independent risk factor for incident AMD. The risk is amplified in individuals with high genetic susceptibility, suggesting a synergistic interplay between inherited genetic risk and somatic clonal expansion in AMD pathogenesis, with the strongest effects observed in older adults. These findings provide a rationale for future efforts to integrate somatic mutation status into risk stratification paradigms for AMD, especially among the elderly.},
}

@article {pmid42419576,
year = {2026},
author = {Renfang-Zhu, and Xu, Y and Nie, M and Li, H and Yuan, Y and Cui, Z and Wang, H and Zhai, Q and He, X and Mao, Y and Wei, Y and Guan, J and Zhang, X and Mao, S},
title = {Virus-biomimetic melanin nanoparticles with spiky structures and neutral zwitterionic shell for non-invasive prevention of dry AMD.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115168},
doi = {10.1016/j.jconrel.2026.115168},
pmid = {42419576},
issn = {1873-4995},
abstract = {Clinically, no effective preventive strategies currently exist to inhibit the progression of early dry age-related macular degeneration (dAMD). Moreover, current retinal therapies rely on intravitreal injections, which carry inherent procedural risks. Inspired by natural melanin and viral structures, we developed virus-biomimetic melanin nanoparticles (VMNPs) surface-modified with ergothioneine (ET), featuring virus-like spike structures and a neutral zwitterionic shell. This study aimed to evaluate whether virus-inspired engineered nanoparticles could enhance retinal delivery and improve the therapeutic potential of melanin-based nanodrugs for dAMD. The VMNPs facilitated cellular uptake through both their virus-mimetic architecture and OCTN1-mediated active transport. They also exhibited potent antioxidant activity, significantly reducing intracellular and mitochondrial reactive oxygen species (ROS) in oxidative stress models of ARPE-19 cells. Transcriptomic analyses revealed that VMNPs activated intrinsic cytoprotective pathways by upregulating HMOX1and SLC7A11, while downregulating inflammation-associated genes. Importantly, VMNPs promoted transcytosis and, following topical administration, demonstrated improved retention and deep penetration within the rabbit eye, effectively reaching the retinal pigment epithelium (RPE) and deeper retinal layers. Notably, twice-daily topical administration of VMNPs markedly inhibited retinal degeneration in rabbits, achieving therapeutic efficacy comparable to a single intravitreal injection of pegcetacoplan. Collectively, these findings establish a promising paradigm for the non-invasive clinical treatment of dAMD.},
}

@article {pmid42421757,
year = {2026},
author = {Olivieri, C and Perin, G and Zhuang, X and Neri, G and Parisi, G and Marolo, P and Viggiano, P and Boscia, F and Reibaldi, M and Borrelli, E},
title = {Baseline Optical Coherence Tomography Biomarkers Associated with the 2-Year Development of Macular Atrophy or Fibrosis in Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101268},
pmid = {42421757},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate baseline structural OCT biomarkers associated with the development of macular atrophy or fibrosis in treatment-naïve eyes with exudative neovascular age-related macular degeneration (AMD) managed with a treat-and-extend (T&E) anti-VEGF regimen.

DESIGN: A retrospective, cohort study.

PARTICIPANTS: Eighty-nine eyes of 89 patients with newly diagnosed exudative neovascular AMD, treated with a T&E regimen and followed for 24 months. Eyes with evidence of macular atrophy or fibrosis at baseline were excluded.

METHODS: Structural OCT scans were assessed at baseline for morphological features including, macular neovascularization (MNV) subtype and presence of subretinal fluid, intraretinal fluid (IRF), subretinal hyperreflective material, hyperreflective foci, and subretinal drusenoid deposits. Two masked graders independently evaluated each scan, with adjudication for discrepancies. Cox regression models were used to determine baseline predictors of macular atrophy and fibrosis over 24 months.

MAIN OUTCOME MEASURES: Development of macular atrophy or fibrosis during 24 months, expressed as hazard ratios (HRs) with 95% confidence intervals (CIs).

RESULTS: During follow-up, 28 eyes (31.5%) developed macular atrophy and 12 eyes (13.5%) developed macular fibrosis, with 10 eyes showing both complications. Multivariate Cox regression identified baseline IRF (HR, 6.07; 95% CI, 2.23-16.48) and type 3 MNV (HR, 4.38; 95% CI, 1.63-11.73) as independent predictors of macular atrophy, whereas type 1 MNV was protective (HR, 0.23; 95% CI, 0.09-0.61). Type 2 MNV emerged as the strongest predictor of macular fibrosis (HR, 7.28; 95% CI, 1.51-35.10).

CONCLUSIONS: Baseline OCT biomarkers, particularly IRF and type 3 MNV, strongly predict macular atrophy, while type 2 MNV predicts fibrosis in eyes with exudative neovascular AMD treated with a T&E regimen. Type 1 MNV may confer protection against atrophy. These exploratory findings underscore the value of comprehensive baseline OCT assessment for anticipating long-term structural outcomes and guiding clinical management.

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

@article {pmid42421758,
year = {2026},
author = {Wright, DM and Trifonov, I and Shahar-Gonen, M and Loewenstein, A and Zur, D and Peto, T},
title = {Machine Learning to Predict Outcomes of Anti-VEGF Therapy in Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101238},
pmid = {42421758},
issn = {2666-9145},
abstract = {OBJECTIVE: To develop machine learning models using OCT fluid metrics to predict long-term anti-VEGF treatment intensity and visual acuity (VA) outcomes in 2 large clinical data sets of patients with neovascular age-related macular degeneration (nAMD).

DESIGN: Retrospective, multicenter cohort study.

SUBJECTS: The study included a total of 2922 eyes from 2475 patients with nAMD treated at 2 tertiary centers in the United Kingdom (Belfast) and Israel (Tel Aviv Medical Center).

METHODS: Longitudinal clinical data and OCT scans obtained at baseline and 6 months after treatment initiation were analyzed using a validated deep learning algorithm to extract quantitative volumetric retinal fluid measurements. Machine learning ensemble models were trained using the Belfast data set to predict total anti-VEGF injections and absolute VA at 1, 2, and 3 years from treatment initiation. External validation was performed by applying the trained models to an independent cohort to assess generalizability across health care systems.

MAIN OUTCOME MEASURES: Prediction accuracy for the total number of anti-VEGF injections and absolute VA at years 1 to 3 since treatment initiation, assessed by agreement with observed outcomes.

RESULTS: In the main cohort, prediction of total anti-VEGF injections was accurate, with 99.6%, 95.5%, and 97.1% of eyes predicted within 2 injections of observed values at years 1, 2, and 3, respectively. Visual acuity predictions were within ≤0.2 logarithm of the minimum angle of resolution units (≤2 ETDRS lines) for 92.5%, 73.5%, and 76.5% of eyes at the corresponding time points. In the external cohort, model performance was reduced, with 45.0% to 53.8% of injection predictions and 26.3% to 41.1% of VA predictions meeting accuracy thresholds. Subretinal fluid at 6 months was the primary driver of injection burden predictions, whereas intraretinal fluid was most influential for VA outcomes.

CONCLUSIONS: Machine learning models based on automated fluid metrics can accurately predict treatment burden and VA outcomes within the clinical environment in which they are developed. Although performance declined with external validation, reflecting differences in treatment policies and health care systems, locally trained models remain clinically valuable. Early identification of high- and low-burden treatment trajectories may support individualized decision-making, patient counseling, and more efficient allocation of ophthalmology resources in the growing nAMD population.

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

@article {pmid42406042,
year = {2026},
author = {Sakai, R and Ichioka, A and Ideyama, M and Akada, M and Ueda-Arakawa, N and Kido, A and Takahashi, A and Miyake, M and Muraoka, Y and Miyata, M and Tamura, H and Ooto, S and Tsujikawa, A and Hata, M},
title = {Association between angiogenic features and responsiveness to faricimab in treatment-naïve neovascular age-related macular degeneration with OCT angiography.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42406042},
issn = {1435-702X},
abstract = {PURPOSE: To investigate morphological changes in macular neovascularization (MNV) using optical coherence tomography angiography (OCTA) and identify imaging biomarkers associated with treatment responsiveness to faricimab in patients with neovascular age-related macular degeneration (nAMD).

METHODS: This prospective study investigated consecutive eyes of patients with treatment-naïve nAMD who were treated with faricimab. After 3-monthly loading doses, the patients received a fixed 8-, 12-, or 16-week treatment regimen (Q8W/Q12W/Q16W) and were grouped as poor responders (Q8W/Q12W) or good responders (Q16W). Dosing interval determination depended on disease activity post-loading phase. Baseline and 14-month quantitative OCTA parameters were analyzed.

RESULTS: Forty-four eyes (pure type 1 MNV: 35 eyes, mixed type 1 and type 2 MNV: 9 eyes) were analyzed. The visual acuity (P < 0.001) and central retinal thickness (P < 0.0001) significantly improved post-faricimab treatment from baseline to Month 14. In mixed type 1 and type 2 MNV, total vessel length decreased from baseline to Month 14 (P < 0.05), whereas vessel area did not significantly change (P = 0.11). No significant changes in total vessel length or vessel area were detected in pure type 1 MNV (P = 0.23 and P = 0.30, respectively). In the subgroup of type 1 MNV, a significant decrease in endpoint density was observed only in good responders (P = 0.04), with no corresponding change in poor responders.

CONCLUSION: A fixed faricimab regimen through Month 14 was associated with improved visual and anatomical outcomes in treatment-naïve nAMD. OCTA-based vascular changes differed according to MNV type and treatment responsiveness. In pure type 1 MNV, endpoint density may be a potential OCTA-based biomarker associated with treatment responsiveness, contributing to a more personalized therapeutic approach for nAMD.},
}

@article {pmid42406913,
year = {2026},
author = {Kuo, BI and Wang, TA and Chu, TC and Chan, DC and Cheng, SY and Tsai, CT and Tsai, CL and Lee, YC and Chen, CJ and Chen, WL and Lee, JT and Tsai, CY and Liu, PY and Chang, CY and Chao, CT and Kao, JH and Hsieh, YT and , },
title = {Artificial Intelligence-Assisted Screening for Patients With Diabetic Retinopathy and Age-Related Macular Degeneration in Family Medicine and Geriatric and Gerontology Care: Protocol for a Pragmatic Randomized Clinical Trial.},
journal = {JMIR research protocols},
volume = {15},
number = {},
pages = {e91699},
pmid = {42406913},
issn = {1929-0748},
mesh = {Humans ; *Diabetic Retinopathy/diagnosis ; *Macular Degeneration/diagnosis ; *Artificial Intelligence ; *Mass Screening/methods ; Pragmatic Clinical Trials as Topic ; Aged ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic ; Family Practice/methods ; Female ; Cost-Benefit Analysis ; Male ; Middle Aged ; },
abstract = {BACKGROUND: Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are 2 of the leading causes of vision loss worldwide. As population aging and diabetes prevalence increase, timely detection of these conditions has become essential. However, limited professionalism and insufficient training in ophthalmic screening among general medicine physicians may lead to delayed diagnosis and treatment. Artificial intelligence (AI)-assisted diagnostic tools may help to improve the screening of DR and AMD in routine clinical practice.

OBJECTIVE: This study aims to evaluate the clinical effectiveness and cost-effectiveness of AI-assisted fundus imaging for DR and AMD screening in adults with diabetes and older adults at risk of macular degeneration.

METHODS: This multicenter, 2-arm, parallel-group, open-label, individual-level randomized controlled trial and patient recruitment are performed at the settings of Family Medicine and Geriatric and Gerontology Care over 4 medical centers in Taiwan. Eligibility includes (1) diabetic individuals aged ≥20 years for DR screening, and (2) individuals aged ≥50 years for AMD screening. The study protocol has been approved by the ethics committees of all participating hospitals, and all participants will provide written informed consent.

RESULTS: The study was funded in September 2024, began on October 2, 2025, and is expected to be completed in December 2027. After the pilot implementation phase without randomization, participants will be randomized 1:1 into two groups: (1) AI-assisted screening, and (2) usual physician-only screening. The primary outcomes will include the detection rates (defined as participants with confirmed DR or AMD among all screened participants) and the positive predictive values (defined as participants with confirmed DR or AMD among those who tested positive). Cost-effectiveness analyses will be performed using data derived from the trial results.

CONCLUSIONS: This study will provide robust evidence on the effectiveness of AI-assisted ophthalmic screening in improving patient eye health outcomes through timely screening and accurate early detection. This strategy may be cost-effective.},
}

Humans
*Diabetic Retinopathy/diagnosis
*Macular Degeneration/diagnosis
*Artificial Intelligence
*Mass Screening/methods
Pragmatic Clinical Trials as Topic
Aged
Randomized Controlled Trials as Topic
Multicenter Studies as Topic
Family Practice/methods
Female
Cost-Benefit Analysis
Male
Middle Aged

@article {pmid42410200,
year = {2026},
author = {Beretta, F and Scalabrin, G and Balduzzi, E and Puligheddu, S and Bandello, F and Sacconi, R and Querques, G},
title = {Real-Life 1-Year Results and Predictors of Visual Outcome with Intravitreal Faricimab for Treatment of Exudative Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42410200},
issn = {2193-8245},
abstract = {INTRODUCTION: The purpose of this study was to report 1-year real-world outcomes of faricimab for the treatment of macular neovascularization secondary to age-related macular degeneration (nAMD). Early predictors of functional outcome were investigated.

METHODS: This was a retrospective, longitudinal study including 132 eyes with nAMD (27% treatment-naïve, 73% switchers) treated with faricimab following a treat-and-extend protocol. Primary outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT) changes at 1-year follow-up. Secondary outcomes included possible early predictors of 1-year functional outcomes. Early predictors were investigated at the baseline and after the loading phase.

RESULTS: After the loading phase, both BCVA (from 0.40 ± 0.33 to 0.35 ± 0.34 LogMAR) and CMT (from 403 ± 135 to 317 ± 108 um) improved significantly (p = 0.014 and p > 0.001 respectively). At 1 year, only CMT reduced significantly (from 403 ± 135 to 317 ± 114 um, p < 0.001), and 36% of eyes were defined as good visual responders (≥ 5 ETDRS letters gain). Predictors of good response were lower BCVA and absence of type 3 macular neovascularization (MNV) at baseline and lower CMT after loading phase. Approximately 60% of patients achieved ≥ Q12-week dosing. Treatment-naïve patients achieved higher extension rates (82% ≥ Q12). No cases of intraocular inflammation were observed.

CONCLUSIONS: In our real-world practice, faricimab effectively controls nAMD, offering significant anatomical benefits and visual stability with extended dosing intervals. Approximately 80% of treatment-naïve patients maintained ≥ Q12-week schedules. Early anatomical response, defined by reduction in CMT and absence of exudative signs on structural optical coherence tomography (OCT), emerged as a clinically relevant prognostic factor for 1-year outcomes.},
}

@article {pmid42410853,
year = {2026},
author = {Song, Y and Ji, H and Xie, D and Huang, F and Yang, L},
title = {Elevated Food Inflammation Scores of individuals is a significant risk factor for age-related macular degeneration in adults in the United States: Evidence from NHANES.},
journal = {Medicine},
volume = {105},
number = {27},
pages = {e49604},
pmid = {42410853},
issn = {1536-5964},
mesh = {Humans ; *Macular Degeneration/epidemiology/etiology ; United States/epidemiology ; Nutrition Surveys ; Female ; Risk Factors ; *Inflammation/complications/epidemiology ; Middle Aged ; Male ; Aged ; Cross-Sectional Studies ; Adult ; *Diet/adverse effects ; },
abstract = {Inflammation has been implicated in the pathogenesis of age-related macular degeneration (AMD). We evaluated whether the inflammatory potential of the diet (quantified using the newly developed Food Inflammation Scores of individuals [FISI]) influences the incidence of AMD. Participants aged > 40 years were included from the National Health and Nutrition Examination Survey database, totaling 5293 participants, of whom 421 had AMD. Logistic regression analysis and restricted cubic spline were used to explore the relationship between FISI and AMD. Linear regression analysis was used to analyze the relationship between FISI and age. Path analysis was used to explore the correlation among age, FISI, and AMD. Subgroup analysis explored the relationship between FISI and AMD in subgroups. Interaction analysis explored the interaction between FISI and other variables on AMD. FISI was significantly higher in the AMD group than in the Non-AMD group. There was a significant positive linear association between FISI and AMD, and a higher FISI was associated with higher odds of AMD (odds ratios [95% confidence interval]: 1.040 [1.015-1.065]). The cross-sectional pattern was consistent with age being associated with AMD partly through FISI. Higher FISI was significantly associated with higher odds of AMD in some subgroups. FISI had no interaction with subgroup variables on AMD. In this nationally representative cross-sectional sample of the United States adults aged ≥ 40 years, a higher FISI was associated with a higher prevalence of AMD. Because the design is cross-sectional and a substantial portion of this association was attributable to age, the results should be interpreted as hypothesis-generating; prospective studies are needed before recommending FISI-guided dietary intervention as a primary-prevention strategy for AMD.},
}

Humans
*Macular Degeneration/epidemiology/etiology
United States/epidemiology
Nutrition Surveys
Female
Risk Factors
*Inflammation/complications/epidemiology
Middle Aged
Male
Aged
Cross-Sectional Studies
Adult
*Diet/adverse effects

@article {pmid42405678,
year = {2026},
author = {Sadeghi, E and Gregori, G and DeCicco, J and Sadeghi, Z and Gandhi, P and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J},
title = {Distinct interactions between macular neovascularization and geographic atrophy: Growth dynamics and fellow-eye risk.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261461910},
doi = {10.1177/11206721261461910},
pmid = {42405678},
issn = {1724-6016},
abstract = {PurposeTo compare geographic atrophy (GA) growth in eyes with and without macular neovascularization (MNV) and evaluate anti-VEGF therapy effects on GA progression.MethodsOne eye per patient with GA with one-year of follow-up was included. Patients who developed MNV in previously diagnosed GA were assigned to the MNV-GA group, while those who did not were assigned to the non-MNV group. OCT determined MNV location and type. GA was quantified from RPE en-face images using ImageJ over one year. Fellow eyes were followed to last visit. Analyses used SPSS with Mann-Whitney U; P < 0.05 denoted significance, and prespecified thresholds applied throughout analyses.ResultsA total of 60 eyes from 60 patients were included (mean age: 82.75 ± 7.31; 56.7% female). A significant difference in GA area growth over one year was observed between two groups, with slower GA enlargement in MNV-GA group (1.15 mm[2] vs. 2.36 mm[2]; P = 0.001; and square root: 0.38 ± 0.28 vs. 0.46 ± 0.36; P = 0.040). In MNV-GA eyes, GA growth showed no correlation with the number of anti-VEGF injections (P = 0.692). Most MNVs were type 1 (46.7%) and type 2 (43.3%) and were predominantly located at the GA border (70.0%), particularly in the central (30.0%) and superior (30.0%) sectors. Among the 60 fellow-eyes, 27 (45.0%) developed MNV during follow-up. Of these, 25 eyes (83.3%) were from patients from MNV-GA group, whereas only 2 eyes (6.7%) were from non-MNV group (P < 0.001).ConclusionEyes with MNV-GA showed slower GA enlargement over one-year, regardless of anti-VEGF frequency, and higher fellow-eye MNV risk, indicating shared risk factors but distinct mechanisms influencing disease progression.},
}

@article {pmid42405917,
year = {2026},
author = {Ying, GS},
title = {Nonsteroidal Anti-inflammatory Drug Use Reduces the Risk of Age-Related Macular Degeneration in Electronic Health Record Analysis: Signal or Solution?.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.06.013},
pmid = {42405917},
issn = {1549-4713},
}

@article {pmid42406041,
year = {2026},
author = {Veritti, D and Sarao, V and Lupidi, M and Viggiano, P and Lombardo, M and Parravano, M and Savastano, MC and Boscia, G and Borrelli, E and Toto, L and Martin, AA and Termite, AC and Ribezzi, G and Nacciarriti, E and Fossataro, C and Gisotti, EN and Neri, G and Persavalli, C and Boscia, F and Mariotti, C and Mastropasqua, R and Reibaldi, M and Ricci, F and Rizzo, S and Savastano, A and Varano, M and Lanzetta, P},
title = {Switching to aflibercept 8 mg in neovascular age-related macular degeneration: real-world outcomes according to switch indication.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42406041},
issn = {1435-702X},
abstract = {PURPOSE: To evaluate visual and anatomical outcomes after switching to aflibercept 8 mg in eyes with neovascular age-related macular degeneration (nAMD), and to assess outcomes according to the clinical indication for switching.

METHODS: Multicentre retrospective observational study including 300 eyes with nAMD previously treated with anti-vascular endothelial growth factor therapy and switched to aflibercept 8 mg for non-response (n:74, 24.7%), suboptimal response (n:159, 53.0%), or durability-driven reasons (n:67, 22.3%). Longitudinal data from the 6 months preceding the switch and post-switch visits at 3 and 6 months were analyzed. The primary outcome was change in best-corrected visual acuity (BCVA, ETDRS letters) from the switch visit to the 3-month post-switch visit. Secondary outcomes included changes in central subfield thickness (CST) and retinal fluid status.

RESULTS: During the pre-switch period, mean BCVA declined by - 1.9 ± 8.2 letters and CST increased. At 3 months after switching, BCVA improved by + 2.0 ± 9.2 letters (95% CI, + 0.8 to + 3.2; p < 0.01), with greater gains in eyes switched for non-response (+ 2.8 ± 12.6 letters). Mean CST decreased by - 45.3 ± 79.8 µm (95% CI, - 55.4 to - 35.2; p < 0.001), with corresponding reductions in retinal fluid. Anatomical improvements were more pronounced in eyes switched for non-response, whereas more modest but consistent changes were observed in suboptimal and durability-driven groups. Visual and anatomical outcomes were maintained at 6 months.

CONCLUSIONS: In previously treated nAMD eyes, switching to aflibercept 8 mg was associated with reversal of pre-switch anatomical worsening, reduction in retinal fluid, and modest visual gains. Greater responses were observed in eyes with inadequate pre-switch disease control, supporting its role as a treatment escalation strategy in clinical practice.},
}

@article {pmid42399507,
year = {2026},
author = {Yuan, H and Hu, Y},
title = {Phenotypic age acceleration and genetic risk synergistically increase age-related eye disease risk in the UK Biobank.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-60932-w},
pmid = {42399507},
issn = {2045-2322},
support = {2026Y0015//Jiangxi Provincial Health Commission Introduced and Cultivated Talents Special Scientific Research Project/ ; 202610039//Jiangxi Provincial Health Commission Science and Technology Plan Project/ ; YK012//2024 Nanchang University Education Development Foundation "Changyi Leading Research" Clinical Scientific Research Project/ ; },
abstract = {To evaluate the independent and synergistic effects of phenotypic age acceleration (PhenoAgeAccel) and genetic risk on age-related eye diseases (AREDs). We analyzed 395,322 participants from the UK Biobank to assess the association between PhenoAgeAccel and polygenic risk scores for age-related macular degeneration (AMD) and age-related cataract (ARC). Cox proportional hazards models evaluated independent effects and potential synergistic interactions, adjusting for demographic, socioeconomic, and lifestyle factors. PhenoAgeAccel was independently associated with increased risk of AMD (HR = 1.15, 95% CI 1.10-1.21) and ARC (HR = 1.14, 95% CI 1.12-1.17). High genetic risk conferred stronger effects for AMD (HR = 1.88, 95% CI 1.78-1.98) and ARC (HR = 1.31, 95% CI 1.27-1.35). Participants with both elevated PhenoAgeAccel and high genetic risk had markedly higher risk (AMD: HR = 2.19; ARC: HR = 1.47) compared with biologically younger, low-risk individuals. A significant multiplicative interaction was observed for AMD, indicating a synergistic effect between accelerated phenotypic aging and genetic susceptibility. PhenoAgeAccel and genetic risk each contribute to the development of AREDs, and their combination exerts a synergistic effect. Integrating aging biomarkers with genetic profiling could enhance risk stratification and inform targeted prevention strategies for ocular health.},
}

@article {pmid42401235,
year = {2026},
author = {Wei, P and Gao, S and Zhang, K and Jia, L and He, M and Lu, J and Li, C and Han, G},
title = {Tanshinone IIA inhibits choroidal neovascularization and restores outer blood-retinal barrier function in Vldlr knockout mice.},
journal = {Experimental eye research},
volume = {271},
number = {},
pages = {111158},
doi = {10.1016/j.exer.2026.111158},
pmid = {42401235},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, with its neovascular form (nAMD) primarily treated using anti-VEGF agents; however, therapeutic resistance and nonresponse remain major clinical challenges. Tanshinone IIA (TIIA), a multi-target bioactive compound derived from Salvia miltiorrhiza, has shown potential in retinal disease treatment. In this study, we investigated the therapeutic effects and underlying mechanisms of TIIA on choroidal neovascularization (CNV) using Vldlr knockout (Vldlr[-/-]) mice as an nAMD model. TIIA was administered intraperitoneally for 8 weeks, and CNV progression and vascular leakage were evaluated by OCT and FFA, while outer blood-retinal barrier (oBRB) integrity was assessed by immunofluorescence staining. Proteomics analysis combined with western blotting was used to explore the molecular mechanisms. Our results showed that TIIA significantly reduced CNV area and leakage, and restored oBRB integrity by upregulating tight junction proteins ZO-1 and Occludin in the RPE/choroid complex. Mechanistically, TIIA inhibited angiogenesis via suppression of the PLCγ/ERK1/2 signaling pathway. In addition, proteomics analysis revealed enhanced cholesterol efflux, intermediate filament reorganization, and decreased autophagy-related proteins across the retina, RPE/choroid complex, and serum. Collectively, these findings demonstrate that TIIA alleviates nAMD pathology through multi-target mechanisms, including inhibition of angiogenesis, restoration of barrier function, metabolic reprogramming, and modulation of autophagy, highlighting its potential as an alternative therapeutic strategy for nAMD.},
}

@article {pmid42401373,
year = {2026},
author = {Ding, J and Su, L and Chen, W and Wu, R and Gao, L},
title = {Notch signaling in anti-VEGF resistant arteriolar choroidal neovascularization.},
journal = {Biochemical pharmacology},
volume = {},
number = {},
pages = {118214},
doi = {10.1016/j.bcp.2026.118214},
pmid = {42401373},
issn = {1873-2968},
abstract = {Choroidal neovascularization (CNV) is a major pathological hallmark of fundus diseases, such as age-related macular degeneration, and is commonly treated with anti-vascular endothelial growth factor (VEGF) agents. However, resistance to or a suboptimal response to anti-VEGF therapy, particularly in arteriolar CNV, remains a significant clinical challenge. Arteriolar CNV, characterized by arterialized vessels, feeding arterioles with high blood flow, and prominent fibrosis, remains persistently active and responds poorly to standard anti-VEGF therapy. Notch signaling confers anti VEGF resistance in various diseases including cancer and corneal neovascularization. However, its role in anti-VEGF resistant arteriolar CNV has not been systematically summarized. This review highlights Notch signaling as a key regulator of both physiological and pathological arterial remodeling, driving arteriolar differentiation and contributing to resistance to VEGF inhibitors. In tumors, Notch signaling plays a crucial role in driving arteriolar neovessel formation, promoting macrophage-mediated vascular remodeling, and enhancing fibrosis, all of which contribute to anti-VEGF resistance. We also discuss whether and how similar mechanisms may operate in arteriolar CNV and proposes that Notch signaling represents a potential therapeutic target. Furthermore,combining Notch inhibitors with anti-VEGF therapy may improve outcomes in patients with arteriolar CNV resistant to anti-VEGF therapy, thereby providing a potential therapeutic strategies. Future studies are warranted to elucidate the specific roles of Notch signaling in CNV and optimize therapeutic strategies for improved safety and efficacy.},
}

@article {pmid42401656,
year = {2026},
author = {Kamiński, P and Brodzka, S and Baszyński, J and Paczała, R and Stanek, E and Rektor, K and Grochowalska, R and Hromada, M and Stuczyński, T and Tkaczenko, H and Woźniak, A and Kurhaluk, N},
title = {Macular degeneration dependent on defense mechanisms conditioned by chemical elements and genetic polymorphism.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-59733-y},
pmid = {42401656},
issn = {2045-2322},
abstract = {Macular degeneration MD is a chronic, lifestyle-related eye disease developing in increasingly younger people. The cause is not fully understood, but oxidative stress is among the most critical factors. The subject of our research is the wet form of MD. The tested materials were whole blood and plasma from 84 patients with exudative MD and from 127 healthy volunteers, from SW Poland. The concentration of toxic metals (Hg, Cd, Pb, As, Be), macroelements (Ca, Mg, Na, K, P) and microelements (Mn, Fe, Zn, Cu, Se, Mo, Cr, Li, V, Co, Ag, Ba, Ti, Tl, Sr, Al, Ni, Sn, B, Sb) was analyzed (ICP-MS) in the blood to determine environmental exposure. The activity of antioxidant enzymes (superoxide dismutase SOD, catalase CAT, glutathione peroxidase GPx, glutathione reductase GR) was determined to demonstrate the ability to eliminate the effects of reactive oxygen species ROS. The activity of nonenzymatic antioxidant mechanisms (reduced glutathione GSH, bilirubin, uric acid, vitamins A and E) was examined to assess the body's ability to activate defense mechanisms against ROS. The intensity of lipoperoxidation (malondialdehyde, MDA), and the importance of ceruloplasmin CP in patients with exudative MD and their exposure to oxidative stress were determined. The presence of glutathione-S-transferase GST polymorphisms (GSTT1, GSTM1) was examined to determine their role in generating MD. The genetic polymorphism of interleukin-4 IL-4 and vascular endothelial growth factor VEGF-A was analyzed, and it was determined whether there is a genetic burden that can potentially increase the chance of developing MD. The activity of SOD, CAT, GPx, and GR, and the activity of nonenzymatic antioxidants (GSH, bilirubin, uric acid, all-trans retinol, and alpha-tocopherol) were determined using Cayman kits and HPLC chromatography. MDA was determined using Cayman reagents, and CP was determined using Wuhan reagents. In our exudative MD patients, P, Ca, Mn, Fe, Cu, and Zn were most involved in interactions, whereas in the control group, Pb, Ca, Mn, Zn, and Ba were most important. In the analysis of antioxidant parameters, significant differences were found between the studied groups for SOD, CAT, GPx, bilirubin, all-trans retinol, alpha-tocopherol, and uric acid. Also, MDA and CP showed significant differences. In MD patients and healthy individuals, many correlations were found. Significant differences were noted for IL-4 in the frequency of the T allele in MD patients, and for Sr. The frequency distributions of GSTT1 and GSTM1 polymorphisms showed no significant differences between the groups, whereas differences were observed for all-trans retinol. Changes within VEGF-A genotypes showed no significant differences between the studied groups (p > 0.5). Due to the presence of mutagenic substances in the environment, the changed genome plays an important role in MD development. The pathogenic process can be observed by analyzing the effectiveness of enzymatic and nonenzymatic mechanisms. The low diagnostic value of MDA and CP for patients with MD was indicated. The results highlighted the significant role of environmental factors and indicated new directions for research into MD etiology. They identified new parameters to be considered when examining predisposition to this disease (Na, P, Cr, Mn, Ba, MDA, bilirubin, A and E vitamins, SOD, CAT, GPx, IL-4). We compare the aspects we examine holistically, making this the first study of this type. Despite many elements of MD development being known so far, there are still many unanswered questions in this field that will require further analysis, especially regarding K, Pb, As, Hg, Cd, Sr, Al, Ba, V, Fe, mutations in IL-4, GSTM1, and GSTT1.},
}

@article {pmid42401735,
year = {2026},
author = {Yu, J and Zhang, Y and Gao, YL and Ho, M and Kam, KW and Gong, B and Young, AL and Pang, CP and Tham, CC and Yam, JC and Chen, LJ},
title = {Association of baseline brain care score with the incidence of age-related eye diseases.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42401735},
issn = {1476-5454},
support = {82425017//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {OBJECTIVES: To evaluate the associations of baseline brain care score (BCS) with the incidence of age-related eye diseases (AREDs), and to examine the modifying effects of age and genetic susceptibility.

METHODS: We included 382,221 UK Biobank participants without cataract, glaucoma, or age-related macular degeneration (AMD) at baseline. Baseline BCS (0-19 point) encompassed physical, lifestyle and social-emotional factors. Higher BCS scores indicated better brain care. Multivariable Cox regression was used to estimate associations between baseline BCS and incident cataract, glaucoma, and AMD. Polygenic risk scores (PRSs) were used to test gene-BCS interactions.

RESULTS: Over a median follow-up of 14.28 (interquartile range: 13.34-15.11) years, 44,033 cataract cases, 9280 glaucoma cases, and 6754 AMD cases were identified. Compared with the lowest baseline BCS quintile, the highest baseline BCS quintile was associated with lower risk of cataract (adjusted hazard ratios [HR]: 0.89, 95% confidence interval [CI]: 0.86-0.92), glaucoma (0.92, 0.86-0.98), and AMD (0.90, 0.83-0.97). Stronger associations of per 5-unit increase in baseline BCS with incident cataract (0.78, 0.71-0.85) and glaucoma (0.72, 0.64-0.83) were observed in participants aged 40-50 years than in older groups, with significant interactions with age (P-interaction < 0.001). A significant interaction between baseline BCS and PRS was observed for cataract (P-interaction < 0.001), but not for glaucoma or AMD.

CONCLUSIONS: Higher baseline BCS is associated with lower long-term risk of AREDs, especially in middle-aged individuals. These findings underscore BCS as a novel and potentially modifiable factor for AREDs.},
}

@article {pmid42402434,
year = {2026},
author = {Arnaiz-Camacho, A and Castany-Aregall, M and Pairó-Salvador, A and García-Hidalgo, S and Pablos-Jiménez, T and Bertolani, Y and Alarcón-Portabella, S and Zapata, MÁ},
title = {The Amapola Test: description of a novel screening tool for visual alterations in primary care.},
journal = {Family practice},
volume = {43},
number = {4},
pages = {},
doi = {10.1093/fampra/cmag034},
pmid = {42402434},
issn = {1460-2229},
support = {//Fundació Catalana d'Oftalmologia (Societat Catalana d'Oftalmologia-SCOFT)/ ; },
mesh = {Humans ; Prospective Studies ; Primary Health Care ; Female ; Male ; *Vision Disorders/diagnosis ; Aged ; Middle Aged ; Aged, 80 and over ; Adult ; *Vision Screening/methods ; *Vision Tests/methods ; Feasibility Studies ; },
abstract = {PURPOSE: To describe a novel screening tool for the detection of visual alterations in primary care.

METHODS: A prospective study was conducted in order to assess concordance and feasibility of the Amapola Test. In patients with a visual complaint, a primary care resident physician identified the visual symptom using the Amapola Test and the results were then compared with an expert history-taking conducted by an ophthalmologist.

RESULTS: The Amapola Test was administered to 350 patients with visual disturbances. Of these, 321 patients identified the symptom on the visual charts. The test showed a high concordance rate, with a usability of 89.4% (95% CI: 86.2%-92.6%). The most frequently identified visual symptoms were blurred vision (109), isolated floaters (75), floaters combined with photopsia (23), and isolated photopsia (20). The most common diagnoses were posterior vitreous detachment (100), migraine visual aura (28), and exudative age-related macular degeneration (19).

CONCLUSION: The Amapola Test allows for correct identification of visual symptoms. This study demonstrates a high level of concordance between patient-reported symptoms using the test and expert clinical history, and indicates potential application as a supportive tool in primary care. However, further studies in real-life settings are needed to demonstrate its usefulness and to evaluate its diagnostic performance.

CLINICAL TRIAL NUMBER: not applicable.},
}

Humans
Prospective Studies
Primary Health Care
Female
Male
*Vision Disorders/diagnosis
Aged
Middle Aged
Aged, 80 and over
Adult
*Vision Screening/methods
*Vision Tests/methods
Feasibility Studies

@article {pmid42403183,
year = {2026},
author = {Yoon, E and Shin, JY and Ahn, J},
title = {Impact of Early Residual Fluid after Aflibercept Loading on 12-Month Outcomes in Neovascular Age-Related Macular Degeneration.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2026.0060},
pmid = {42403183},
issn = {2092-9382},
abstract = {PURPOSE: To evaluate the impact of early residual fluid (ERF) following aflibercept loading on 12-month anatomical and functional outcomes in patients with neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective study included 111 eyes of 107 treatment-naïve nAMD patients. ERF was defined as the presence of intraretinal fluid (IRF) and/or subretinal fluid (SRF) observed after three loading doses of aflibercept. Patients were divided into ERF (n = 28) and ERF-free (n = 83) groups. Best-corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at baseline, post-loading, and at 12 months. Subgroup analyses were conducted based on fluid location within the ERF group.

RESULTS: ERF was observed in 25.2% of eyes after loading. The ERF group exhibited significantly greater CMT at all time points (P < 0.050). Although BCVA did not differ significantly between groups, the ERF group required a significantly higher injection burden (7.36 ± 1.95 vs. 5.29 ± 1.44; P = 0.001). Subgroup analysis within the ERF group revealed that eyes with IRF had worse baseline BCVA (P = 0.038) and a higher rate of persistent IRF at 12 months (87.5%). Multivariate analysis identified post-loading ERF (OR: 3.41, P = 0.046), thicker post-loading CMT (OR: 1.01, P = 0.030), and higher injection frequency (OR: 1.31, P = 0.022) as independent predictors of residual fluid at 12 months.

CONCLUSIONS: ERF after aflibercept loading is a significant independent predictor of long-term fluid persistence. While ERF signifies a more recalcitrant disease course, comparable visual outcomes can be achieved through proactive, individualized treatment.},
}

@article {pmid42404552,
year = {2026},
author = {Macha, NN and Yu, M and Naqvi, S and Birch, D and Tolentino, M and Callanan, D and Maturi, RK},
title = {Multifocal Electroretinography Outcomes Following AVD-104 Treatment for Geographic Atrophy.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261438431},
pmid = {42404552},
issn = {2474-1272},
abstract = {Purpose: To assess the treatment effect of AVD-104 in eyes with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD) by multifocal electroretinography (mfERG) and evaluate mfERG as a potential clinical endpoint in dry AMD studies. Methods: This prospective case series included 6 patients enrolled in part 1 of the phase 2/3 SIGLEC clinical trial, all of whom were diagnosed with advanced bilateral GA. Subjects received a single intravitreal injection of AVD-104 in the study eye. At a screening visit, baseline, and months 1, 2, and 3, mfERG testing and best-corrected visual acuity (BCVA) were collected in the study eyes. mfERG testing was also collected at a screening visit, baseline, and month 3 in fellow eyes. We analyzed the overall N1-P1 response density, overall P1 implicit time, junctional N1-P1 response density, and junctional P1 implicit time at each visit. Results: After AVD-104 treatment, the largest improvements in mean overall N1-P1 response density and junctional N1-P1 response density occurred at month 2, with gains of 17.1% (P = .47) and 40.1% (P = .01), respectively. Five of 6 study eyes achieved a greater than 20% gain in mean junctional N1-P1 response density at month 2, and 3 study eyes maintained more than a 20% gain at month 3. Mean BCVA also improved incrementally at each follow-up visit, reaching +6.0 letters over baseline at month 3 (P = .04). Conclusions: mfERG and BCVA data supported the benefit of AVD-104 treatment in eyes with GA and revealed the potential to recover retinal function in the junctional zone 2 months after treatment.},
}

@article {pmid42404560,
year = {2026},
author = {Zhou, F and Bai, W and Zhao, Y and Jiang, Q and Wang, C and Xu, X and Yao, J},
title = {Short-term outcomes of intravitreal faricimab on refractory neovascular age-related macular degeneration patients in China.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1855248},
pmid = {42404560},
issn = {2296-858X},
abstract = {PURPOSE: To assess the real-world clinical outcomes of faricimab in patients receiving treatment for neovascular age-related macular degeneration (nAMD).

METHODS: This real-world prospective observational study included patients with refractory nAMD. In total, 37 patients were analyzed. All patients had previously undergone at least three consecutive intravitreal injections of other anti-vascular endothelial growth factor (anti-VEGF) agents. The primary outcomes were best-corrected visual acuity (BCVA) and anatomical outcomes on optical coherence tomography angiography (OCTA) at a four-month follow-up period.

RESULTS: The faricimab regimen resulted in significant improvements in both visual and anatomical parameters among patients with refractory nAMD. LogMAR BCVA decreased substantially from 0.82 ± 0.42 to 0.57 ± 0.32 (p < 0.001). Central subfield thickness (CST) was reduced significantly from 336.89 ± 141.52 μm to 244.19 ± 69.91 μm (p < 0.001). The pigment epithelial detachment (PED) area decreased from 1.30 ± 0.71 to 0.94 ± 0.55 mm[2] (p < 0.001), and the choroidal neovascularization (CNV) area shrank from 1.11 ± 0.64 to 0.97 ± 0.56 mm[2] (p < 0.001). Both the subretinal fluid (SRF) and SRF & Intraretinal fluid (IRF) subgroups exhibited notable improvements in both vision and anatomical structure. Eyes with isolated SRF achieved longer dosing interval extensions (66.7% reached ≥3 months) compared to the SRF & IRF group (47% reached ≥3 months).

CONCLUSION: Faricimab given as three monthly loading doses demonstrates significant short-term improvement in vision and anatomical outcomes, including rapid gains in BCVA and reductions in CST and retinal fluid. It appears effective and well-tolerated for refractory nAMD, particularly in reducing SRF and improving visual acuity, though its effect on IRF resolution was limited and not statistically significant. However, because the study design confounded drug switch with increased injection frequency, the independent contribution of faricimab itself cannot be determined. No adverse safety signals were observed.},
}

@article {pmid42405673,
year = {2026},
author = {Zong, Y and Fan, Q and Qiu, S and Zhang, H and Cen, Z},
title = {The Molecular Basis of Ocular Aging: Mechanisms, Pathologies, and Emerging Therapeutics.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {8},
pages = {13},
doi = {10.1167/iovs.67.8.13},
pmid = {42405673},
issn = {1552-5783},
mesh = {Humans ; *Aging/physiology ; Animals ; Cellular Senescence/physiology ; Mitochondria ; *Macular Degeneration/metabolism ; *Diabetic Retinopathy ; *Eye Diseases/therapy ; *Glaucoma ; Epigenesis, Genetic ; },
abstract = {Age-related eye diseases (AREDs)-including age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy-are leading causes of permanent blindness. Current treatments manage clinical manifestations but do not halt the molecular processes that drive disease progression. This limitation has shifted attention toward "geroscience," a strategy that targets the fundamental biology of aging rather than treating each disease in isolation. Four key hallmarks of aging-mitochondrial dysfunction, loss of proteostasis, cellular senescence, and epigenetic drift-are widely implicated in AREDs. We review evidence that these hallmarks do not act independently; instead, they form an interactive, self-reinforcing network. The way this network engages differs from tissue to tissue. In the high-energy environment of the retinal pigment epithelium, mitochondrial dysfunction dominates and drives AMD. In the mechanically stressed trabecular meshwork (TM), senescence and epigenetic drift take precedence, leading to glaucoma. In the neurovascular unit, chronic hyperglycemia routes the same network into a metabolic-epigenetic amplification loop that sustains diabetic retinopathy. The same aging mechanisms, routed through distinct tissue contexts, thus produce divergent clinical phenotypes. We also evaluate emerging therapies, including senolytics, mitochondria-targeted agents, and partial epigenetic reprogramming, and identify key intervention nodes such as NLRP3, p62, and NAD[+] metabolism. Dismantling these pathological feedback loops offers a path beyond symptom management toward combination strategies that restore tissue resilience.},
}

Humans
*Aging/physiology
Animals
Cellular Senescence/physiology
Mitochondria
*Macular Degeneration/metabolism
*Diabetic Retinopathy
*Eye Diseases/therapy
*Glaucoma
Epigenesis, Genetic

@article {pmid42398914,
year = {2026},
author = {Garweg, JG and Chaudhary, V and Zhang, X and Leal, S and Machewitz, T and Munk, MR and Zarranz-Ventura, J and Stahl, A and Lanzetta, P and , },
title = {Effect of key baseline disease characteristics on aflibercept 8 mg dosing interval extension: A post hoc 96-week analysis of PULSAR.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.06.032},
pmid = {42398914},
issn = {2468-6530},
abstract = {OBJECTIVE: Post hoc analysis of the PULSAR Phase 3 trial (NCT04423718) to describe whether dosing interval outcomes were associated with key baseline disease characteristics.

DESIGN: Exploratory post hoc analysis of PULSAR, a 96-week, double-masked, active-controlled, randomized clinical trial in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) treated with aflibercept 8 mg or aflibercept 2 mg. For the main analysis, patients receiving aflibercept 8 mg were grouped according to their last assigned dosing interval at Weeks 48 and 96.

PARTICIPANTS: Patients with treatment-naïve nAMD who were randomly assigned to receive aflibercept 8 mg in PULSAR.

INTERVENTION: Aflibercept 8 mg was administered every 12 weeks (8q12) or 16 weeks (8q16) following 3 initial monthly injections. Dosing intervals could be shortened in Year 1 based on prespecified disease activity criteria, whereas in Year 2, both interval shortening and extension were allowed. Patients were monitored every 4 weeks but assessed for interval modification at dosing visits only.

MAIN OUTCOME MEASURES: Baseline best-corrected visual acuity (BCVA), central retinal thickness (CRT), and macular neovascularization (MNV) area were assessed in patients grouped by their last assigned dosing interval (Q8, Q12, Q16, Q20, or Q24) at Weeks 48 and 96.

RESULTS: In 86.6% and 78.4% of patients assigned to the 8q12 and 8q16 arms in PULSAR, respectively, randomized dosing intervals were maintained or extended through Week 96. In the 8q12 arm, no trends were observed in baseline BCVA, CRT, and MNV area across groups based on patients' last assigned dosing intervals. In the 8q16 arm, no trends were observed in baseline BCVA across treatment arms; however, patients with shorter last assigned dosing intervals (Q8 and Q12) at Weeks 48 and 96 tended to have a greater baseline CRT or MNV area compared with patients with longer dosing intervals (Q16 to Q24).

CONCLUSIONS: Overall, findings from this PULSAR post hoc analysis of key baseline characteristics in patients grouped by dosing interval suggest that the aflibercept 8q12 and 8q16 regimens were suitable for most patients across a broad range of baseline BCVA, CRT, and MNV area values, with a large proportion of patients able to achieve and maintain extended dosing intervals through Week 96.},
}

@article {pmid42396341,
year = {2026},
author = {Siraz, S and Kamanda, H and Nabil, AS and Gholami, S and Rao, NT and Ong, SS and Alam, MN},
title = {Sequential Deep Learning to Predict Non-Central to Central Geographic Atrophy Progression from OCT Imaging.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.06.17.26355882},
pmid = {42396341},
abstract = {PURPOSE: To develop and validate a temporal deep learning framework for predicting geographic atrophy (GA) progression across multi-year horizons using longitudinal optical coherence tomography (OCT) sequences.

DESIGN: Retrospective longitudinal cohort study.

A total of 91 patients with dry age-related macular degeneration (AMD) were identified from Wake Forest University School of Medicine (2013-2023), yielding 455 OCT volumes. Two prediction cohorts were defined: 32 patients with no GA (NGA) at baseline who subsequently developed GA, and 35 patients whose earliest GA manifestation was non-central GA (NCGA). Non-progressing patients served as negative controls.

METHODS: OCT B-scan volumes were encoded into visit-level feature representations using three pretrained architectures (ResNet-18, ResNet-50, ViT-B/16). Chronologically ordered visit embeddings, optionally augmented with inter-visit time intervals (Δt), were processed through recurrent neural networks (RNN), long short-term memory networks (LSTM), and Transformer encoders to model longitudinal disease trajectories. Models were trained and evaluated independently for prediction horizons of 2, 3, 4, 5, and 6 years using patient-level stratified splits (80/20). Performance was assessed across five random seeds.

MAIN OUTCOME MEASURES: Area under the receiver operating characteristic curve (ROC-AUC), F1-score, and accuracy for predicting two clinically critical transitions: NGA to GA onset and NCGA to central GA (CGA) involvement.

RESULTS: For NGA to GA prediction, models achieved ROC-AUC of 0.84-0.94 at 2-4 years and 1.00 at 5-6 years. For NCGA to CGA prediction, Transformer-based models achieved peak AUC of 0.95 (±0.11) at 4 years and 0.96 (±0.06) at 5 years. Longer input sequences (8 visits vs. 4 visits) consistently improved NCGA to CGA performance at extended horizons. Temporal interval encoding improved stability in several LSTM configurations.

CONCLUSIONS: Temporal deep learning applied to longitudinal OCT sequences can predict GA progression across clinically meaningful 2-6 year horizons without pixel-level annotations. These findings support the feasibility of automated, individualized risk stratification to guide complement inhibitor therapy decisions in patients with GA.},
}

@article {pmid42397104,
year = {2026},
author = {Olevson, C and Kramer, B and Terveen, DC and Berdahl, JP and Thompson, V and Ferguson, TJ},
title = {Light adjustable lens implantation with cataract surgery in eyes with macular pathology.},
journal = {Journal of cataract and refractive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.jcrs.0000000000002017},
pmid = {42397104},
issn = {1873-4502},
abstract = {PURPOSE: To evaluate the visual, refractive and safety outcomes of the light adjustable lens (LAL) in eyes with pre-existing macular pathology undergoing cataract surgery.

SETTING: Private practice, multiple locations.

DESIGN: Retrospective, consecutive case series.

METHODS: Patients with macular pathology undergoing cataract surgery with LAL implantation were included. Diagnoses comprised epiretinal membrane (ERM), dry age-related macular degeneration (AMD)/drusen, and other macular conditions. Primary outcome measures included uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and the percentage of eyes within ±0.25 D (diopter), ±0.50 D and ±1.00 D of the refractive target. Safety endpoints included intraoperative and postoperative complications and changes in CDVA pre- and post-adjustments.

RESULTS: 171 eyes from 106 patients were included. The most common diagnoses were ERM and dry AMD. Among eyes targeted for distance (n=95), 96% achieved UDVA of 20/25 or better and 85% achieved 20/20 or better. For refractive accuracy, 87% of eyes were within ±0.50 D and 68% were within ±0.25 D of the target. The percentage of eyes within ±0.50 D of target rose from 66% to 87% following the adjustment process and the percentage of eyes achieving 20/20 or better climbed from 26% to 85%.

CONCLUSIONS: In eyes with macular pathology, the LAL provides excellent uncorrected visual acuity and highly accurate refractive outcomes with a favorable safety profile. These findings position the LAL as a viable advanced IOL option in patients traditionally considered suboptimal candidates due to underlying macular disease.},
}

@article {pmid42397425,
year = {2026},
author = {Grün, M and Rothaus, K and Beger, A and Winter, C and Lommatzsch, A and Faatz, H},
title = {[Real-world experience with aflibercept 8 mg for treatment of neovascular age-related macular degeneration after 12 months].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42397425},
issn = {2731-7218},
abstract = {BACKGROUND: The phase 3 clinical trial PULSAR demonstrated extended treatment intervals with aflibercept 8 mg in treatment-naïve eyes with neovascular age-related macular degeneration (nAMD) in a large proportion of the cohort, with good drug safety. Early clinical experience in real-world settings confirmed the efficacy in both treatment-naïve and pretreated patients but no data on longer observation periods are available yet.

OBJECTIVE: The aim of the study was to investigate the efficacy, treatment frequency and tolerability of aflibercept 8 mg over a period of 12 months in a group of pretreated nAMD patients.

MATERIAL AND METHODS: A retrospective study of 73 eyes with nAMD and pretreatment with anti-VEGF switched to aflibercept 8 mg. Eyes were initially uploaded with 3 monthly intravitreal injections (IVI), followed by a pro re nata (PRN) regimen. Outcome parameters included visual acuity development and central retinal thickness (CSRT) after upload and 12 months, treatment frequency in the year before and after switching to aflibercept 8 mg, and the overall tolerability of the drug.

RESULTS: Of the initial 73 eyes, 27 eyes (37.0%) were still receiving aflibercept 8 mg after 12 months. In these eyes CSRT was reduced from 387.9 ± 138.4 µm initially to 305.5 ± 93.2 µm after upload and 328.9 ± 105.6 µm after 12 months (p < 0.001). Visual acuity remained stable (p > 0.05). Compared to the year prior to switching, the injection frequency was reduced from 8.2 ± 2.1 to 6.9 ± 1.0 IVIs (p < 0.005). During the observation period, a total of 5 eyes (6.8%) developed noninfectious intraocular inflammation (IOI), with all cases completely regressing with topical treatment.

CONCLUSION: These results confirm a good efficacy of aflibercept 8 mg for the treatment of nAMD with reduced injection frequency after 12 months of treatment in a portion of pretreated eyes that were often previously refractory to treatment. Longer observation intervals and experience with other treatment regimens are necessary to confirm this observation.},
}

@article {pmid42397502,
year = {2026},
author = {Dugiełło, B and Bujała, K and Bolek, B and Wylęgała, A and Wylęgała, E},
title = {Identification of OCTA Biomarkers and Cutoff Values Associated with Disease Severity in Dry Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42397502},
issn = {2193-8245},
abstract = {INTRODUCTION: Optical coherence tomography angiography (OCTA) enables noninvasive assessment of retinal and choroidal microvasculature and may provide quantitative biomarkers of disease severity in dry age-related macular degeneration (AMD). This study aimed to identify OCTA-derived vascular parameters associated with consecutive stages of dry AMD and determine cutoff values for stage differentiation.

METHODS: This cross-sectional study included 182 eyes of 123 participants. Eyes were classified according to the Beckman classification into control, early, intermediate, and late dry AMD groups. OCTA imaging was performed using the ZEISS PLEX Elite 9000 swept-source OCTA system. Quantitative analysis of the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) was conducted using AngioTool software. Vessel density, vessel length, junction-related parameters, endpoints, and lacunarity were analyzed. Group comparisons were performed using analysis of variance (ANOVA) or the Kruskal-Wallis test with post hoc analysis. Receiver operating characteristic (ROC) curves were used to evaluate diagnostic performance and determine optimal cutoff values.

RESULTS: In the SCP, vessel density decreased from 43.83 ± 2.08% in controls to 41.27 ± 3.96% in intermediate AMD (p < 0.001), and mean lacunarity increased from 0.05 ± 0.01 to 0.07 ± 0.03 (p < 0.001), while other parameters showed no significant differences. In the DCP, vessel density declined from 51.71 ± 2.38% in controls to 48.73 ± 4.66% and 43.80 ± 4.98% across disease stages (p < 0.001), with total vessel length decreasing from 73.32 ± 2.72 to 61.58 ± 6.69 (p < 0.001), indicating progressive vascular simplification. The most pronounced changes were observed in the choriocapillaris, where vessel density decreased from 63.28 ± 0.94 to 60.31 ± 1.83% and 26.62 ± 22.30% (p < 0.001), and total vessel length from 102.80 ± 2.24 to 35.68 ± 38.42 (p < 0.001). ROC analysis identified SCP mean lacunarity (cutoff 0.0575, AUC 0.76) as a marker of early disease. In the DCP, total number of junctions below 254 and total vessel length below 66.10 were associated with advanced disease. The highest diagnostic performance was observed for choriocapillaris parameters, including vessel density below 57.38 and total vessel length below 91.10, with sensitivity exceeding 94% and specificity above 80%.

CONCLUSION: OCTA-derived microvascular parameters demonstrate layer-specific alterations in dry AMD. Mean lacunarity in the SCP appeared to be the most sensitive marker of early changes, whereas reductions in junction density and total vessel length in the DCP reflected progressive vascular simplification. The strongest association with disease severity was observed in the choriocapillaris, particularly for vessel density and total vessel length. The identified cutoff values for DCP and CC parameters were associated with different stages of dry AMD and may support stage differentiation and quantitative assessment of disease severity in clinical settings.},
}

@article {pmid42008392,
year = {2026},
author = {Bedersdorfer, M and von Ehrlich-Treuenstätt, G and Früh, T and Boden, KT and Szurman, P and Stanzel, BV},
title = {Visual and Microperimetry Outcomes of an Extended Macular Vision Intraocular Lens in Macular Atrophy.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-9},
doi = {10.1159/000552124},
pmid = {42008392},
issn = {1423-0267},
abstract = {INTRODUCTION: This study aimed to evaluate visual acuity and microperimetry correlated with anatomical changes in eyes with macular diseases implanted with the EyeMax Mono intraocular lens (IOL) (SharpView Ophthalmology).

METHODS: A single-center retrospective, real-world case series was set in Knappschaft Eye Hospital, Sulzbach, Germany. Patients with macular disease who underwent EyeMax Mono IOL implantation were included. The outcome measures were corrected distance visual acuity (CDVA) and microperimetry indices: fixation stability and bivariate contour ellipse areas (BCEAs) at 63% and 95%. The geographic atrophy (GA) monitor (RetInSight) was used to analyze changes in retinal integrity.

RESULTS: Twenty-one eyes (11 patients; mean age 72.8 ± 8.3 years, mean follow-up 7.4 ± 4.0 months) were included. Preoperative GA measured 4.7 ± 4.0 mm2 (n = 14), and EZ loss on SD-OCT was 2,433.1 ± 1,009.5 µm (n = 17). The CDVA improved by 0.2 logMAR (p = 0.007, n = 21), with 12 eyes gaining ≥1 line and seven eyes gaining ≥3 lines. Fixation stability improved in two eyes, stabilized in nine eyes, and worsened in four eyes. The changes in BCEA were not statistically significant. Higher preoperative BCEA correlated with greater postoperative improvement (p < 0.001). In the foveal fixation group (n = 4), 75% and 50% of patients showed improved BCEA and CDVA, respectively. In extrafoveal fixation (n = 11), BCEA improved in 50% of patients, while 64% showed CDVA improvement. The GA monitor showed worsening in 9/15 eyes, and 4 eyes showed worsening on microperimetry without a CDVA decline. Anatomical changes stabilized in six eyes; of these, two exhibited a decline in microperimetry without a CDVA decline.

CONCLUSIONS: EyeMax Mono IOL improved CDVA, although no significant changes were observed in the microperimetry indices. Better microperimetry outcomes were observed in extrafoveal fixation cases. While the optical design of the IOL likely contributes to visual improvement, the small sample size limited the statistical power to detect significant microperimetry changes.},
}

@article {pmid42390573,
year = {2026},
author = {Nagar, NB and Ostrovsky, M and Shoham-Hazon, N and Tuli, R and Lee, TKM and Buchnick, N and Beluga, S and Bramnik, L and Shcolnik, E and Goldfeather Ben Zaken, S and Levy, N and Bareket, M and Berco, E},
title = {Real-world comparison of faricimab and aflibercept as second-line therapies 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 = {42390573},
issn = {1435-702X},
abstract = {PURPOSE: To compare real-world effectiveness of faricimab versus aflibercept as second-line therapies for neovascular age-related macular degeneration (nAMD).

METHODS: This multicenter retrospective cohort study included patients with nAMD who switched to faricimab or aflibercept as second-line anti-VEGF therapy and were followed ≥ 12 months. Outcomes included best-corrected visual acuity (BCVA, logMAR), central macular thickness (CMT, µm), injection intervals, and switching rates. Multivariable linear regression identified predictors of visual and anatomical change.

RESULTS: A total of 170 eyes (84 faricimab, 86 aflibercept) were analyzed. Faricimab-treated eyes had worse baseline BCVA (0.60 ± 0.49 vs. 0.47 ± 0.37 logMAR; p = 0.048) and numerically lower baseline CMT (332.7 ± 107.9 vs. 367.5 ± 103.5 μm; p = 0.057). At final follow-up, faricimab achieved a significant BCVA gain (- 0.16 ± 0.42 logMAR; p < 0.001), while aflibercept maintained stable vision (p = 0.923). Both agents significantly reduced CMT (p < 0.001), with a greater mean reduction observed in the aflibercept group (- 96.7 ± 127.5 vs. - 56.8 ± 132.0 μm; p = 0.046). Final BCVA and CMT did not differ significantly between groups. Final injection intervals were similar between groups (7.5 ± 2.9 vs. 7.6 ± 3.1 weeks; p = 0.906), and switching to third-line therapy occurred less frequently in the faricimab group (4.8% vs. 12.8%; p = 0.065). Baseline BCVA predicted visual gain (B = - 0.199; p = 0.010) and baseline CMT predicted anatomical improvement (B = - 0.517; p < 0.001).

CONCLUSION: In this real-world multicenter cohort, both faricimab and aflibercept were associated with visual and anatomical improvement after switching to second-line therapy for nAMD. No statistically significant difference in final BCVA, final CMT or injection interval was observed between treatment groups. Baseline disease severity predicted treatment response. Given the retrospective design and residual confounding, these findings should be interpreted as associative rather than causal.},
}

@article {pmid42391281,
year = {2026},
author = {Yoshida, N and Kobayakawa, Y and Funakoshi, K and Kimura, S and Hosoya, K and Shinkawa, Y and Furukawa, T and Mitsutake, T and Hoshiko, T and Takamori, A and Kawahara, N and Terasaki, H and Oishi, A and Koizumi, H and Inoue, T and Takeda, A and Ikeda, Y and Yoshida, S and Morizane, Y and Kadonosono, K and Inoue, M and Kamei, M and Todaka, K and Sonoda, KH and Enaida, H},
title = {Protocol for the SACLA trial: Efficacy and safety of subretinal monteplase for submacular hemorrhage in a phase II single-arm multicenter decentralized clinical trial.},
journal = {PloS one},
volume = {21},
number = {7},
pages = {e0353127},
pmid = {42391281},
issn = {1932-6203},
mesh = {Humans ; *Retinal Hemorrhage/drug therapy ; *Tissue Plasminogen Activator/administration & dosage/therapeutic use/adverse effects ; Multicenter Studies as Topic ; Clinical Trials, Phase II as Topic ; Treatment Outcome ; *Fibrinolytic Agents/administration & dosage/therapeutic use ; Vitrectomy ; Visual Acuity ; Female ; },
abstract = {Submacular hemorrhage (SMH), which may arise from age-related macular degeneration, retinal arterial macroaneurysm, and other causes, can result in severe vision loss and central visual field impairment. Although tissue plasminogen activator (tPA) is used off-label to treat SMH in many countries, no formulation has been approved for this indication. Because early intervention is critical when tPA is used for SMH, limited access to centers that can provide this treatment may delay care and reduce treatment opportunities. Decentralized clinical trials (DCTs) reduce or eliminate the need for participants to travel to trial sites. We therefore designed the investigator-initiated SACLA trial to evaluate subretinal tPA for SMH. The DCT framework is intended to reduce logistical barriers related to the disease severity and rarity. The SACLA trial is a phase II multicenter, open-label, single-arm surgical study with a pre-post comparison design (jRCT2071250003). Twenty eligible participants will undergo pars plana vitrectomy followed by subretinal injection of 0.1 mL (8,000 IU) of tPA. Participants will remain hospitalized at the trial site until the primary outcome, change in central foveal thickness (CFT) from baseline at Week 1, is assessed. Thereafter, follow-up visits will be conducted at either the trial site or partner sites within the DCT framework. Secondary efficacy outcomes include change in CFT from baseline, presence of a foveal hemorrhage measuring at least 1 disc diameter, best-corrected visual acuity (BCVA), and change in BCVA from baseline at Weeks 4 and 12. Adverse events will be collected throughout the 12-week observation period to assess safety. The protocol and related study documents were reviewed and approved by the Saga University Hospital Institutional Review Board. This study is designed to generate prospective evidence on the feasibility, short-term anatomical response, and safety of subretinal tPA for SMH.},
}

Humans
*Retinal Hemorrhage/drug therapy
*Tissue Plasminogen Activator/administration & dosage/therapeutic use/adverse effects
Multicenter Studies as Topic
Clinical Trials, Phase II as Topic
Treatment Outcome
*Fibrinolytic Agents/administration & dosage/therapeutic use
Vitrectomy
Visual Acuity
Female

@article {pmid42392211,
year = {2026},
author = {Eiselen, C and Long, M and Chong, EW},
title = {Age-related macular degeneration: Updates for general practitioners.},
journal = {Australian journal of general practice},
volume = {55},
number = {7},
pages = {455-460},
doi = {10.31128/AJGP-10-25-7882},
pmid = {42392211},
issn = {2208-7958},
mesh = {Humans ; *Macular Degeneration/diagnosis/physiopathology/therapy ; Australia/epidemiology ; Risk Factors ; *General Practitioners/trends ; Aged ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness in Australians over 50 years, accounting for 60% of all blindness. AMD progresses from asymptomatic early and intermediate stages to late neovascular ('wet') or atrophic ('dry') forms that cause irreversible central vision loss. Age and family history are the strongest risk factors, while smoking, poor diet and cardiovascular disease are key modifiable contributors.

OBJECTIVE: To raise awareness of AMD in general practice and provide some advice on what general practitioners (GPs) can do to assist in early detection and prevention with an ageing population. GPs can examine the macula in at-risk adults, as well as encourage smoking cessation, a Mediterranean-style diet, regular exercise, and Age- Related Eye Disease Study 2 (AREDS2) supplementation for intermediate disease. Sudden distortion or vision loss requires urgent ophthalmology referral for possible neovascular AMD.

DISCUSSION: Intravitreal anti-VEGF (vascular endothelial growth factor) therapy remains the mainstay for wet AMD, while complement inhibitors show promise for geographic atrophy. Emerging gene, sustained-delivery and laser therapies might soon reduce treatment burden and improve adherence.},
}

Humans
*Macular Degeneration/diagnosis/physiopathology/therapy
Australia/epidemiology
Risk Factors
*General Practitioners/trends
Aged

@article {pmid42392259,
year = {2026},
author = {Priya, S and McLellan, FC and Wich, PR and Kumeria, T and Willcox, M and Shu, DY},
title = {Fumaric Acid Esters as Modulators of Ocular Inflammation and Angiogenesis.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2026.05.014},
pmid = {42392259},
issn = {1525-2191},
abstract = {Ocular diseases leading to irreversible vision loss are driven by convergent pathological processes, including chronic inflammation, oxidative stress, and angiogenesis. Despite therapeutic advances, corneal neovascularization, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma remain major causes of vision impairment. Conventional therapies for these diseases pose challenges related to non-responsiveness and long-term inefficacy, highlighting the need for treatments that target upstream mechanisms shared across ocular pathologies. Fumaric acid esters (FAEs), particularly dimethyl fumarate (DMFu) and its active metabolite, monomethyl fumarate (MMF), have emerged as promising drug candidates due to their potent immunomodulatory and antioxidant properties. Mechanistically, DMFu activates nuclear factor erythroid 2-related factor 2 (Nrf2) signaling to enhance antioxidant defense while suppressing nuclear factor-κB (NF-κB)-mediated pro-inflammatory responses. Beyond inflammation, DMFu inhibits VEGF-driven angiogenesis through metabolic rewiring in endothelial cells. This review discusses the efficacy of FAEs across various ocular pathologies and addresses the pharmacokinetics of the drugs and hurdles such as rapid systemic hydrolysis and ocular barriers. Despite translational challenges, the multimodal mechanisms of FAEs offer a unique advantage over single-target therapies, positioning them as promising candidates for targeting convergent pathways in complex ocular diseases.},
}

@article {pmid42392261,
year = {2026},
author = {Yao, PL and Malek, G},
title = {Lxrα Deficiency Primes Retinal Degeneration, but Aging Drives Disease Severity.},
journal = {The American journal of pathology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajpath.2026.05.012},
pmid = {42392261},
issn = {1525-2191},
abstract = {The liver X receptor alpha (LXRα) regulates serum cholesterol and lipoprotein levels under homeostatic conditions and in response to dietary fat. Previously aged Lxrα[-]/[-] mice fed a standard diet were shown to develop phenotypes resembling early age-related macular degeneration (AMD). Herein, the hypothesis tested was that introducing a high-fat, high-cholesterol (HFC) diet in young Lxrα[-]/[-] mice could bypass aging and accelerate onset of AMD-like pathology. Young Lxrα[+]/[+] and Lxrα[-]/[-] mice (2-3 months old) were fed either a standard diet or an HFC diet for up to two months. Retinal function and morphology were assessed by electroretinography and fundus/OCT imaging, histopathology was evaluated by transmission electron microscopy, and retinal markers were examined by immunostaining. Young Lxrα[-]/[-] mice fed an HFC diet exhibited impaired retinal function with reduced scotopic a- and b-waves, photopic b-waves, and c-waves. While the retinal ultrastructure of control and HFC-fed Lxrα[+]/[+] mice appeared normal, HFC-fed Lxrα[-]/[-] mice showed RPE thinning, disorganized basal infoldings, intracellular lipid droplets, thin basal laminar deposits, and Bruch's membrane thickening enriched in apolipoprotein E. Increased microglia/macrophage infiltration in the retina and choroid suggested elevated local inflammation. Although an HFC diet accelerated AMD-like changes in young Lxrα[-]/[-] mice, these lesions were less severe than those observed in aged Lxrα[-]/[-] mice on a standard diet, indicating that aging remains the dominant driver of disease severity.},
}

@article {pmid42393152,
year = {2026},
author = {Samra, N and Moustafa, H and Aouf, M and Samra, WA and Abdelslam, MM},
title = {Dual branch fundus deep learning network as an enhanced multi classification system for ocular disease detection via hybrid feature fusion.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-58277-5},
pmid = {42393152},
issn = {2045-2322},
abstract = {Ophthalmic diagnosis relies heavily on the interpretation of fundus images to identify a range of debilitating diseases. However, the presence of multiple, co-existing pathologies and the subtle visual cues associated with early-stage disease pose a significant challenge, necessitating the development of advanced diagnostic tools. We present DFD-Net (Dual-Branch Fundus Deep Learning Network), a deep learning solution that performs multi-label classification of various ocular diseases. The system achieves this by integrating the attribute maps from bilateral retinal photographs, like those from the right and left eyes. This study starts with a thorough pre-processing operation on the fundus images, represented in image rescaling, black border image cropping, contrast enhancement, and data augmentation of retinal photographs. Following this, the processing pipeline begins with a dual-branch feature extraction framework. A part of the system employs a ConvNeXt architecture to obtain complex semantic characteristics, while the parallel branch employs a U-Net encoder to capture fine-grained, structural characteristics across several scales. These complementary feature representations are then combined via a fusion mechanism. The fused feature representations are subsequently enhanced by a SENet Block for greater robustness through channel-wise recalibration. The resulting feature maps are reduced via Global Average Pooling, and then passed through a Dense layer for feature refinement. Finally, the features are classified by a Softmax output layer, consistent with the single-label multi-class formulation adopted in this work, to identify one of eight possible categories. The testing was implemented on the Ocular Disease Intelligent Recognition-Ophthalmic Image analysis (OIA-ODIR) dataset, which has retinal photographs that represent six distinct ophthalmic categories, macular degeneration, cataracts, glaucoma, hypertension, diabetic retinopathy, and myopia, images that present normal cases, and images that represent multiple other diseases, depicting eight different categories. The proposed DFD-Net system established precision, recall, F1- scores, and overall accuracy of 92.75%, 93.17%, 94.45%, and 93.77% on the On-Site testing collection and 91.50%, 93.19%, 92.11%, and 92.97% on the Off-Site testing collection, respectively. Ultimately, the suggested DFD-Net system proved high efficiency in precisely classifying multiple ocular diseases, offering a novel and outstanding approach for early detection of fundus diseases.},
}

@article {pmid42394911,
year = {2026},
author = {Cui, H and Wu, H and Zhao, B and Zhao, Y and Zhang, C and Wang, M and Zhang, J and Wang, K and Wang, Y and Song, Z and Tao, Y},
title = {Harnessing nanotechnology: Transforming ocular drug delivery with advanced hydrogel systems.},
journal = {Bioengineering & translational medicine},
volume = {11},
number = {4},
pages = {e70099},
pmid = {42394911},
issn = {2380-6761},
abstract = {Ocular drug delivery faces tremendous challenges in clinical practice. The eyeball possesses sophisticated anatomical and physiological characteristics that uniquely influence the pharmacokinetics of delivered drugs. This complexity necessitates innovative solutions to ensure effective drug delivery. Conventional ocular drug administration routes (topical, intravitreal, and systemic) each pose unique limitations. With the advancements of biomaterials science and medical engineering technology, nanofiber hydrogels have garnered significant attention, primarily represented by self-assembled peptide-based hydrogels and cellulose nanofiber-based hydrogels. They can be tailored to have precise physical and chemical properties, enabling controlled release of drugs and enhanced biocompatibility. Furthermore, their nanofibrous structure mimics the extracellular matrix, promoting cell adhesion and tissue regeneration. This review introduces advanced manufacturing techniques which are capable of precisely modifying the properties of nanofiber hydrogels to meet specific therapeutic needs. The distinctive advantages of nanofiber hydrogels are elaborated in detail, including their ability to enhance drug penetration, provide sustained release, and reduce systemic toxicity. We also delve into the therapeutic applications, potential limitations, and developmental perspectives of nanofiber hydrogels. Preclinical studies have validated their efficacy in treating ophthalmologic conditions such as age-related macular degeneration, bacterial keratitis, ocular alkali burns, and non-infectious uveitis. However, translating these laboratory findings into clinical applications remains limited, primarily due to significant challenges in human trials, including species-specific responses, the complexity of human biology, and the safety of nanofiber hydrogels. Future refinements in fabrication techniques and rigorous safety assessments are necessary to revolutionize the clinical application of nanofiber hydrogels.},
}

@article {pmid42395092,
year = {2026},
author = {Nelson, AJ and Kastelein, JJ and Ditmarsch, M and Hall, C and Kling, D and Ortiz, N and Wicks, DL and Hsieh, A and Szarek, M and Ray, KK and Davidson, MH and Nicholls, SJ},
title = {Obicetrapib safety analysis: Pooled phase 3 clinical trial experience.},
journal = {American journal of preventive cardiology},
volume = {28},
number = {},
pages = {101547},
pmid = {42395092},
issn = {2666-6677},
abstract = {BACKGROUND: Obicetrapib is a potent, selective cholesteryl ester transfer protein (CETP) inhibitor that lowers LDL-C and raises HDL-C. Although prior studies have demonstrated efficacy and general tolerability, a comprehensive evaluation of its safety profile across later-stage clinical trials is needed.

METHODS: Safety outcomes were assessed in a pooled analysis of two phase III trials comparing obicetrapib 10 mg daily with placebo in adults with heterozygous familial hypercholesterolemia (HeFH) or atherosclerotic cardiovascular disease (ASCVD). Participants received treatment for 365 days. Safety endpoints included treatment-emergent adverse events (TEAEs) and prespecified events of special interest including hepatic, muscular, glycemic, renal and ocular parameters as well as overall rates of discontinuation.

RESULTS: A total of 2,880 participants were included (mean age 64 years; 36 % female; 82 % with ASCVD; 35.8 % with diabetes). Overall TEAE rates were similar between obicetrapib and placebo (60.2 % vs 62.0 %). AEs leading to treatment discontinuation occurred in 4.1 % of obicetrapib-treated participants and 5.3 % on placebo, Risk Ratio (RR) 0.77 [0.54-1.08]. No clinically significant change in blood pressure was observed between groups and hypertension events were comparable. There was no difference between the groups in liver or muscle-related endpoints. Reduction in eGFR occurred less often with obicetrapib (compared to placebo (6.7 % vs. 8.7 % RR 0.77 [0.59, 1.00])). Macular degeneration was reported once in the obicetrapib group (n= 1 [0.1 %]). Deaths were similar between treatment groups. No new safety signals were identified.

CONCLUSIONS: Obicetrapib demonstrated a favorable safety profile over 12 months, with AE rates comparable to placebo. These findings extend our understanding of the safety and tolerability of obicetrapib.},
}

@article {pmid42395855,
year = {2026},
author = {Kim, D and Stunkel, L},
title = {Retrograde Maculopathy or Microcystic Macular Degeneration in Patients With Optic Neuritis due to Neuromyelitis Optica.},
journal = {Case reports in ophthalmological medicine},
volume = {2026},
number = {},
pages = {2502132},
pmid = {42395855},
issn = {2090-6722},
abstract = {PURPOSE: The aim of this study is to highlight findings of retrograde maculopathy (RM) on optical coherence tomography (OCT) as a sequela of neuromyelitis optica associated optic neuropathy.

OBSERVATIONS: We report two patients with demyelinating lesions involving the visual pathways due to neuromyelitis optica in whom RM was seen, and in whom the location of the RM corresponded to their visual deficits. In one case, we describe a patient who had a demyelinating chiasmal lesion with bitemporal hemianopia and who had corresponding binasal RM. In another case, we describe a patient who had generalized vision loss in the right eye and who had corresponding diffuse RM in the right macula.

CONCLUSIONS AND IMPORTANCE: RM is a potential sequela of severe optic neuropathy in neuromyelitis optica and topographically corresponds to severe visual field defects, as well as severe ganglion cell complex loss. Providers should recognize this finding and be aware that they do not need to pursue diagnostic evaluation due to concern for primary macular disease.},
}

@article {pmid42384341,
year = {2026},
author = {Wang, L and Guo, ZY and Hu, FX and Zhang, CY and Yuan, Y and Zhou, BQ and Peng, YT and Pang, L and Wang, Y},
title = {Next-generation sequencing reveals aqueous MicroRNA and piRNA signatures in age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {Molecular and cellular biochemistry},
volume = {},
number = {},
pages = {},
pmid = {42384341},
issn = {1573-4919},
support = {82405485//National Natural Science Foundation of China/ ; 2023A03J0751//Guangzhou Science and Technology Program/ ; YN2023WSSQ06//Special Research Project in Guangdong Provincial Hospital of Chinese Medicine/ ; },
abstract = {MicroRNAs (miRNAs) play important roles in the pathogenesis of age-related macular degeneration (AMD), while whether polypoidal choroidal vasculopathy (PCV) represents a subtype of AMD remains controversial. However, the differential small non-coding RNA profiles in aqueous humor (AH) between neovascular AMD (nAMD) and PCV remain insufficiently characterized. Therefore, this study aimed to characterize miRNA and piRNA expression profiles in AH samples from nAMD and PCV patients and to explore the potential involvement of these small non-coding RNAs in angiogenesis-related pathways. AH samples were collected from nine cataract controls, eight treatment-naïve nAMD patients, and eight treatment-naïve PCV patients. Small RNA profiles in AH were analyzed using next-generation sequencing (NGS). Differential expression analysis was performed using DESeq2 with adjustment for age, sex, best-corrected visual acuity (BCVA), intraocular pressure (IOP), batch effects, and quality-control covariates. Target gene prediction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. Selected miRNAs were partially validated by quantitative PCR (qPCR). To further evaluate their potential relevance to angiogenesis, expression levels of selected miRNAs were additionally examined in a laser-induced choroidal neovascularization (CNV) mouse model. A total of 35 differentially expressed miRNAs were identified between nAMD and PCV, including 28 upregulated and 7 downregulated miRNAs. Moreover, 27 and 47 uniquely expressed miRNAs were detected in nAMD and PCV, respectively. Four miRNAs exhibited opposite expression patterns between the two diseases. Functional enrichment analysis revealed significant involvement of Hippo, MAPK, and neurodegeneration-related signaling pathways. qPCR validation confirmed the differential expression of miR-150-5p and VEGF. In the laser-induced CNV mouse model, miR-150-5p showed expression changes consistent with the human AH sequencing results. Distinct miRNA and piRNA expression profiles were identified between nAMD and PCV, suggesting differential molecular mechanisms underlying the two diseases. These findings improve our understanding of AMD and PCV pathogenesis and may provide potential biomarkers for disease differentiation and angiogenesis-related research.},
}

@article {pmid42385173,
year = {2026},
author = {Colijn, JM and Holz, FG and Pas, J and Hoyng, C},
title = {Retinal dystrophies simulating geographic atrophy: A diagnostic challenge.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70184},
pmid = {42385173},
issn = {1755-3768},
abstract = {Geographic atrophy (GA) is the chronic loss of retinal pigment epithelium, photoreceptors and choriocapillaris, marking the dry late stage of age-related macular degeneration (AMD). GA prevalence is expected to rise in the upcoming decades. Advanced GA leads to central scotomas, reducing visual acuity and quality of life, potentially resulting in profound central vision loss. GA shares features with various retinal diseases and can therefore be complicated to distinguish from mimicking diseases. While no cure exists for GA, therapies like pegcetacoplan and avacincaptad aim to slow atrophy growth, making an accurate diagnosis essential for effective treatment. Misdiagnosis can lead to inappropriate treatment recommendations, impacting patient health and financial burden. This paper outlines the similarities and differences among prevalent diseases such as late-onset Stargardt disease, PRPH2-associated disease and maternally inherited diabetes and deafness (MIDD), resembling GA to aid in accurate diagnosis.},
}

@article {pmid42385795,
year = {2026},
author = {Zhou, Q and Zhang, Z and Wu, Y and Dong, C and Wu, CC and Handa, JT and Ma, J and Wang, S},
title = {A Critical Role for Mitochondrial Dynamics in Cigarette Smoke Condensate-induced RPE Senescence.},
journal = {Free radical biology & medicine},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.freeradbiomed.2026.06.060},
pmid = {42385795},
issn = {1873-4596},
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Its pathogenesis remains incompletely understood, partly due to the complex interplay of genetic risk, aging, and environmental stressors. Cigarette smoking (CS) is a major modifiable risk factor for AMD, yet the mechanism linking CS to disease progression remains unclear. We hypothesize that CS accelerates AMD pathogenesis by exacerbating cellular senescence in the retinal pigment epithelium (RPE), thereby driving age-related RPE dysfunction and degeneration. In this study, differentiated ARPE-19 cells or mice were exposed to low-dose cigarette smoke condensate (CSC), and stress-induced senescence-like RPE phenotypes were induced, characterized by increased senescence markers, mitochondrial dysfunction, and retinal functional impairment. RPE senescence phenotypes were also confirmed in mice exposed to 6 months of CS in the smoking chamber. CSC-induced RPE senescence was associated with a biphasic alteration in mitochondrial morphology, progressing from early mitochondrial fragmentation to late mitochondrial hyperfusion, as well as impaired mitophagy flux, reduced mitochondrial turnover, and decreased mitochondrial biogenesis. Mechanistically, CSC increased dynamin-related protein 1 (DRP1) phosphorylation and promoted cleavage of the mitochondrial phosphatase PGAM5, mitochondrial remodeling associated with decreased DRP1 activities, elevated mitochondrial oxidative stress, and activation of mTOR signaling. Notably, overexpression of a DRP1 activity mutant (K38A) mimics the CSC-induced RPE senescence, while overexpression of the phosphodeficient DRP1-S637A mutant significantly attenuates both mTOR signaling and CSC-induced RPE senescence by restoring mitochondrial fission balance, improving mitochondrial quality-control responses, reducing mitochondrial oxidative stress. Collectively, these findings identify impaired DRP1-dependent mitochondrial remodeling as a key mechanism linking CSC exposure to RPE senescence. While we confirmed the RPE senescence phenotype in mice after 6 months of CS exposure, the specific mechanisms observed in this study require further validation in a chronic CS model. These findings encourage future research into mitochondrial dynamics and RPE senescence in AMD, suggesting that modulating RPE mitochondrial dynamics holds therapeutic potential for delaying AMD progression.},
}

@article {pmid42386027,
year = {2026},
author = {Sheibani, N and Wang, S and Darjatmoko, SR and Sorenson, CM},
title = {Caffeine suppresses inflammation and subretinal fibrosis through modulation of the thrombospondin-1-Bim axis.},
journal = {Experimental eye research},
volume = {271},
number = {},
pages = {111152},
doi = {10.1016/j.exer.2026.111152},
pmid = {42386027},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) in the aging population frequently leads to vision impairment. Treatment for neovascular AMD (nAMD) focuses on the tortuous leaky vessels that typify choroidal neovascularization (CNV). Subretinal fibrosis in nAMD patients is more challenging to treat, as few effective options exist. This fibrosis notably impairs vision and typically develops in patients who do not fully respond to current treatments. To gain a better understanding of pathways that could be utilized to subvert subretinal fibrosis, we examined the role Bim, a pro-apoptotic mediator in the intrinsic cell death pathway, and thrombospondin-1 (TSP1), a key regulator of ocular angioinflammatory processes, have in moderating fibrosis. Here we show caffeine treatment significantly reduced subretinal fibrosis in the mouse laser photocoagulation model consistent with its known ability to enhance mononuclear phagocyte (MP) clearance and reduce CNV. Since the TSP1-Bim axis facilitates MP clearance, suppresses inflammation, prevents subretinal fibrosis and CNV, we assessed its necessity for the mitigation of fibrosis by caffeine. We show that caffeine did not prevent subretinal fibrosis or CNV in mice lacking Bim or TSP1. Thus, caffeine utilizes the intrinsic death pathway though TSP1-Bim axis to subvert subretinal fibrosis, likely by suppressing inflammation during CNV.},
}

@article {pmid42386395,
year = {2026},
author = {Vingopoulos, F and Katz, R and Patel, NS and Garg, I and Lu, ES and Laíns, I and Kasetty, M and Silverman, RF and Nigalye, A and Kim, L and Husain, D and Miller, JW and Vavvas, DG and Miller, JB},
title = {Reference map of multimodal vision deficits in intermediate age-related macular degeneration: contrast sensitivity and low-contrast visual acuity.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329091},
pmid = {42386395},
issn = {1468-2079},
abstract = {PURPOSE: To provide a reference map of deficits in contrast sensitivity (CS) and low-contrast visual acuity (LCVA) across stages of non-exudative age-related macular degeneration (AMD) and evaluate functional consequences of optical coherence tomography structural biomarkers.

METHOD: Prospective cross-sectional study of 509 eyes of 358 subjects: 317 dry AMD eyes (99 early, 177 intermediate, 41 advanced), 192 healthy control eyes. Reference limits defined from control eye measures of best-corrected visual acuity (BCVA), quantitative contrast sensitivity function (CSF) measures of LCVA, area under the logarithm CSF (AULCSF), CS at multiple frequencies. Risk scores defined by the sum of structural biomarkers in each eye were associated with visual outcomes across and within AMD stages using multiple linear regression analyses.

RESULTS: Compared with controls, AULCSF declined by 2.2 decibels (dB) in early AMD (eAMD), 3.7 dB in intermediate AMD (iAMD) and 8 dB in advanced AMD. Proportions iAMD eyes breaching reference limits: 50% for AULCSF, 36% for BCVA, 39% for LCVA. For eAMD and iAMD, risk scores were significantly correlated with AULCSF (p<0.02) and CS at low frequencies (1-3 cpd, p<0.005) but not BCVA and LCVA (p>0.05). High-risk eyes breached 1-3 cpd reference limits at higher rates (60-68%) than low-risk eyes (24-30%). AULCSF and LCVA deficits were presented on a novel map of multimodal vision loss.

CONCLUSION: The functional consequences of AMD structural biomarkers were validated by structure-function analyses. We provide a reference map of multimodal vision deficits in AMD for CS and LCVA that could be useful to follow the progression of vision loss in AMD in routine clinical practice and as a clinical trial endpoint.},
}

@article {pmid42386641,
year = {2026},
author = {Otsu, W},
title = {[Light stress-induced damage to intracellular membrane organelles and its preventive strategies].},
journal = {Nihon yakurigaku zasshi. Folia pharmacologica Japonica},
volume = {161},
number = {4},
pages = {257-262},
doi = {10.1254/fpj.26030},
pmid = {42386641},
issn = {0015-5691},
mesh = {Humans ; *Light/adverse effects ; Animals ; *Oxidative Stress ; Mitochondria/radiation effects ; *Intracellular Membranes/radiation effects ; Blue Light ; Endoplasmic Reticulum/radiation effects ; },
abstract = {Photoreceptor cells in the retina are highly specialized sensory cells that function as light receptors. During the conversion of light into neural signals, photoreceptors are constantly exposed to oxidative stress. Although environmental stressors, such as excessive light exposure, have been implicated in the progression of various retinal diseases, including dry age-related macular degeneration (AMD), the molecular mechanisms underlying the light-induced stress response remain incompletely elucidated. Excessive light exposure triggers the endoplasmic reticulum (ER) stress response in cells and also induces mitochondrial dysfunction characterized by depolarization and fragmentation, ultimately leading to cell death. We have shown that compounds derived from natural products, such as delphinidins and pentadecyl, exert protective effects against blue light-induced cellular damage. Furthermore, crocetin, a natural carotenoid pigment, has been shown to suppress ultraviolet-A (UV-A)-induced mitochondrial fragmentation in corneal epithelial cells. In this review, we provide an overview of light stress-induced injuries to intracellular membrane organelles, particularly mitochondria and the ER, and the cellular response mechanisms that are mediated through these organelles. These findings suggest that maintaining the homeostasis of intracellular membrane organelles represents an important therapeutic target for the prevention and treatment of retinal degenerative diseases.},
}

Humans
*Light/adverse effects
Animals
*Oxidative Stress
Mitochondria/radiation effects
*Intracellular Membranes/radiation effects
Blue Light
Endoplasmic Reticulum/radiation effects

@article {pmid42387875,
year = {2026},
author = {Zhao, Q and Xie, Z and Zhao, X and Wei, L and Cheng, S and Gu, X and Chen, Y},
title = {Distinguish polypoidal choroidal vasculopathy through choroidal alterations: A systematic review, meta-analysis and narrative synthesis.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70190},
pmid = {42387875},
issn = {1755-3768},
support = {82271112//National Natural Science Foundation of China/ ; kyfyjj202506//Peking Union Medical College Hospital Research Funding for Postdoc/ ; },
abstract = {PURPOSE: Polypoidal choroidal vasculopathy (PCV) is a vision-threatening choroidal vascular abnormality historically categorized as a subtype of neovascular age-related macular degeneration (nAMD). Accumulating evidence suggests that PCV may instead belong to the pachychoroid spectrum diseases, although its choroidal characteristics remain incompletely characterized and inconsistently reported.

METHODS: PubMed, Embase and Ovid were searched for studies comparing choroidal structural and vascular parameters of PCV with healthy controls (HC), fellow eyes, nAMD or pachychoroid spectrum diseases. Outcomes supported by three or more studies were synthesized using quantitative meta-analysis, whereas outcomes supported by fewer than three studies were summarized using narrative synthesis and exploratory meta-analysis.

RESULTS: Forty studies were included in the final analysis. Meta-analysis revealed that subfoveal choroidal thickness (SFCT) was significantly greater in PCV eyes than in HC, nAMD, and fellow eyes, but lower than central serous chorioretinopathy and pachychoroid neovasculopathy (PNV) eyes (all p < 0.05). PCV eyes also had lower choroidal vascularity index within the standard subfoveal width of 1.5 mm and higher choroidal vascular density (CVD) within the r = 10 mm FOV than HC eyes (p < 0.05). Narrative synthesis and exploratory meta-analysis suggested that PCV eyes may have greater total choroidal thickness than HC and nAMD eyes, as well as a higher ratio of Haller layer thickness to SFCT and larger choroidal luminal area than nAMD eyes at specific locations or areas. Besides, thick-choroid PCV demonstrated higher CVD in 200° ultra-wide ICGA images than nAMD, while the thin-choroid subtype exhibited lower CVD than PNV.

CONCLUSIONS: PCV is characterized by a thicker and more vascular choroid than nAMD and HC, but a thinner and less vascular choroid than CSC and PNV. These findings, supported by both primary and exploratory meta-analyses, provide insights into PCV pathogenesis and its distinction from nAMD and other pachychoroid spectrum disorders.},
}

@article {pmid42388147,
year = {2026},
author = {Agrawal, BK and Charan, GS and Bharti, R and Phougat, J and Kaur, M},
title = {Effectiveness of an Educational Intervention to Assess Knowledge and Attitudes Regarding Age-related Macular Degeneration among Nursing Students.},
journal = {Annals of African medicine},
volume = {},
number = {},
pages = {},
doi = {10.4103/aam.aam_400_26},
pmid = {42388147},
issn = {0975-5764},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults. This study aimed to assess the effectiveness of an educational intervention in improving nursing students' knowledge and attitudes toward AMD.

MATERIALS AND METHODS: A quasi-experimental pretest-posttest design was conducted with 144 nursing students from M. M. Institute of Nursing, Haryana. A structured knowledge questionnaire and attitude scale were used to assess the students before and after the intervention. The educational intervention, delivered via PowerPoint presentation, covered AMD's definition, prevalence, risk factors, clinical features, management, and the nursing role in AMD care.

RESULTS: The results indicated that in the pretest, 44.4% of the students demonstrated good knowledge, which increased to 79.2% in the posttest. Positive attitude improved from 77.8% to 85.4%, while neutral attitude decreased from 22.2% to 14.6%. In terms of knowledge, the mean score improved from 21.78 ± 6.29 in the pretest to 26.34 ± 5.07 in the posttest, showing a statistically significant improvement (P = 0.001). For attitude, the mean score increased from 54.09 ± 6.00 in the pretest to 55.73 ± 5.98 in the posttest, with a statistically significant improvement (P = 0.021). Therefore, the educational intervention significantly enhanced nursing students' knowledge and attitudes toward AMD.

CONCLUSION: The educational intervention significantly improved nursing students' knowledge and attitudes toward AMD. These findings emphasize the need to integrate eye health education into nursing curricula to enhance the effective management of AMD so that nursing students can manage patients with AMD in the community as well as in hospitals.},
}

@article {pmid42388256,
year = {2026},
author = {Zhou, L and White, E and Matteson, A and Andrews, A and Bailey, ST and Lujan, BJ and Jia, Y and Huang, D and Chen, S},
title = {Split-Spectrum Amplitude-Decorrelation Optoretinography Detects Impaired Photoreceptor Function in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {8},
pages = {101250},
pmid = {42388256},
issn = {2666-9145},
abstract = {PURPOSE: To assess photoreceptor functional impairment in eyes with early-to-intermediate age-related macular degeneration (AMD) using OCT-based split-spectrum amplitude-decorrelation optoretinography (SSADOR).

DESIGN: Prospective observational comparative study.

PARTICIPANTS: Adults ≥50 years of age with early or intermediate AMD and age-matched control subjects.

METHODS: Split-spectrum amplitude-decorrelation optoretinography measures flash-evoked OCT amplitude fluctuations within the photoreceptor outer segment band to objectively quantify photoreceptor light responses. We compared SSADOR mean decorrelation between AMD and control eyes within the central 3-mm macula and across ETDRS subfields and evaluated associations with best-corrected visual acuity (BCVA) and drusen volume.

MAIN OUTCOME MEASURES: Split-spectrum amplitude-decorrelation optoretinography mean decorrelation within ETDRS subfields, as a surrogate marker of the light sensing function of photoreceptors.

RESULTS: Twenty-two eyes with early-to-intermediate AMD and 12 control eyes were enrolled in the study. Split-spectrum amplitude-decorrelation optoretinography decorrelation was significantly reduced in AMD eyes compared with controls across all ETDRS subfields (all P < 0.05), with the greatest reduction in the fovea (P < 0.001). Although visual inspection showed localized reductions over large drusen, regression analysis revealed no meaningful correlation between SSADOR and drusen volume. In AMD eyes, foveal SSADOR decorrelation was moderately associated with BCVA (R[2] = 0.349, P = 0.0002). Split-spectrum amplitude-decorrelation optoretinography distinguished AMD eyes from controls with higher accuracy than BCVA (area under the receiver operating characteristic curve 0.989 vs. 0.795; DeLong test P = 0.002).

CONCLUSIONS: Split-spectrum amplitude-decorrelation optoretinography detected impaired photoreceptor light responses in eyes with early-to-intermediate AMD compared with age-matched controls and outperformed BCVA in differentiating AMD from normal eyes. Split-spectrum amplitude-decorrelation optoretinography decorrelation may serve as a sensitive, objective biomarker for detecting and monitoring early or subtle photoreceptor dysfunction in AMD.

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

@article {pmid42388486,
year = {2026},
author = {Zang, H and Han, L and Shi, D},
title = {Risk factors for age-related macular degeneration: an umbrella analysis of systematic review and meta-analysis.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1878292},
pmid = {42388486},
issn = {2296-858X},
abstract = {BACKGROUND: The objective of the current study was to conduct an umbrella review of meta-analyses to systematically assess the methodological quality, potential biases, and validity of all epidemiological evidence addressing risk factors associated with age-related macular degeneration (AMD), and to synthesize the available evidence regarding AMD risk factors.

METHODS: We searched PubMed, Web of Science, Embase, and the Cochrane Database of Systematic Reviews to April 2025 (last update) for systematic reviews and meta-analyses that focused on the risk factors for AMD. The methodological quality of each study was assessed independently by two reviewers using AMSTAR and the GRADE framework.

RESULTS: Following a comprehensive systematic search, a total of 53 distinct risk factors were identified, comprising 30 factors with statistically significant associations and 23 without significant associations. Based on the GRADE framework, most of the evidence was classified as low or very low quality, with three factors achieving a moderate level of evidence. Consistent associations were observed for age and smoking, as well as for certain lifestyle and systemic factors, including diet, diabetes, and hypertension. Circulating biomarkers, including carotenoids, C-reactive protein (CRP), and high-density lipoprotein cholesterol (HDL-C), were also found to be associated with AMD, although the strength of evidence varied across studies.

CONCLUSION: This umbrella review indicates that AMD risk is associated with multiple modifiable lifestyle and systemic factors. Healthy diet and physical activity may have protective roles, while several circulating biomarkers, including carotenoids and C-reactive protein, have been identified as related to AMD risk. However, given that most of the available evidence is of low or very low certainty, these findings should be considered with caution.

PROSPERO, CRD420251045558, URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251045558.},
}

@article {pmid42389069,
year = {2026},
author = {Şatırtav, G and Lövestam-Adrian, MK and Chang, W and Charles, M and Chen, LJ and Cheung, CMG and Kodjikian, L and Ohji, M and Zinkernagel, M and Wolf, S},
title = {Discontinuing Anti-VEGF Therapy in Patients with Neovascular Age-Related Macular Degeneration That Remains Inactive with Treatment at the Maximum Injection Interval.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {587803},
pmid = {42389069},
issn = {1177-5467},
abstract = {This review aims to provide guidance on the management of patients with neovascular age-related macular degeneration (nAMD) whose disease becomes inactive on anti-vascular endothelial growth factor (VEGF) treatment. The Vision Academy's membership of international retinal disease experts reviewed the literature and developed consensus recommendations and an algorithm to determine the appropriate timing of treatment suspension and a post-treatment follow-up strategy for appropriate patients with nAMD who achieve a good response to anti-VEGF therapy. Patients with inactive disease (defined as absence of both intraretinal and subretinal fluid, absence of deterioration in vision, and absence of new retinal hemorrhage) for at least three consecutive maximum treatment intervals as outlined in the clinic's protocol may be considered for treatment exit. However, in patients with stable disease that remains active and those with only one good seeing eye and a history of disease recurrence, treatment continuation may be preferred. An appropriate interval for continued monitoring with optical coherence tomography and visual acuity testing should be decided following discussion with the patient and consideration of patient-specific factors. This article presents consensus guidelines for nAMD management in patients who respond well to anti-VEGF therapy, and for the discontinuation of treatment in cases of success.},
}

@article {pmid42389194,
year = {2026},
author = {Shao, N and Tan, K and Chen, P and Luo, Q},
title = {Multi-omics triangulation identifies complement factor H as a genetically supported protective factor in IgA nephropathy.},
journal = {Clinical kidney journal},
volume = {19},
number = {7},
pages = {sfag176},
pmid = {42389194},
issn = {2048-8505},
abstract = {BACKGROUND: IgA nephropathy is the most prevalent primary glomerulonephritis globally. Dysregulation of the complement system, specifically the alternative pathway, is a critical driver of its pathogenesis. While genome-wide association studies consistently map a primary susceptibility locus to the complement factor H gene cluster, extensive linkage disequilibrium and complex structural variations have historically obscured precise causal targets.

METHODS: We employed a multi-omics triangulation framework to evaluate the genetic association and potential protective effects of circulating complement proteins in IgA nephropathy. The analytical pipeline integrated large-scale plasma proteomics, blood-derived expression quantitative trait loci, Bayesian colocalization, computational clinical transcriptomics, and phenome-wide association studies. Two-sample, bidirectional, and multivariable Mendelian randomization analyses were performed using summary-level data from global genome-wide association studies.

RESULTS: Genetically predicted higher circulating levels of complement factor H were significantly associated with a lower risk of IgA nephropathy. Bayesian colocalization decoupled the complex locus, isolating this protective signal to a single missense variant within the complement factor H gene and demonstrating independence from the adjacent complement factor H-related 1 gene. Spatial profiling and clinical transcriptomics suggested a dual-compartment model: the liver supplies the systemic pool, while intrinsic renal cells mount a hypothesized severity-driven compensatory upregulation of complement factor H during active disease. Furthermore, phenome-wide association studies indicated that enhancing complement factor H offers dual protective benefits against IgA nephropathy and age-related macular degeneration without broad chronic systemic pleiotropy.

CONCLUSIONS: This study provides convergent genomic and transcriptomic evidence supporting complement factor H as a genetically supported protective factor in IgA nephropathy. Genetic variation consistent with enhanced complement factor H-mediated regulation is associated with reduced disease susceptibility. These findings provide a theoretical framework for exploring direct recombinant supplementation therapies and offer genetic support for the ongoing clinical development of upstream alternative pathway inhibitors.},
}

@article {pmid42389246,
year = {2026},
author = {Gu, R and Hou, B and Hébert, M and Indurkar, A and Yang, Y and Chew, EY and Keenan, TDL and Lu, Z},
title = {Toward Multimodal Conversational AI for Age-Related Macular Degeneration.},
journal = {ArXiv},
volume = {},
number = {},
pages = {},
pmid = {42389246},
issn = {2331-8422},
abstract = {Despite strong performance of deep learning models in retinal disease detection, most systems produce static predictions without clinical reasoning or interactive explanation. Recent advances in multimodal large language models (MLLMs) integrate diagnostic predictions with clinically meaningful dialogue to support clinical decision-making and patient counseling. In this study, OcularChat, an MLLM, was fine-tuned from Qwen2.5-VL using simulated patient-physician dialogues to diagnose age-related macular degeneration (AMD) through visual question answering on color fundus photographs (CFPs). A total of 705,850 simulated dialogues paired with 46,167 CFPs were generated to train OcularChat to identify key AMD features and produce reasoned predictions. OcularChat demonstrated strong classification performance in AREDS, achieving accuracies of 0.954, 0.849, and 0.678 for the three diagnostic tasks: advanced AMD, pigmentary abnormalities, and drusen size, significantly outperforming existing MLLMs. On AREDS2, OcularChat remained the top-performing method on all tasks. Across three independent ophthalmologist graders, OcularChat achieved higher mean scores than a strong baseline model for advanced AMD (3.503 vs. 2.833), pigmentary abnormalities (3.272 vs. 2.828), drusen size (3.064 vs. 2.433), and overall impression (2.978 vs. 2.464) on a 5-point clinical grading rubric. Beyond strong objective performance in AMD severity classification, OcularChat demonstrated the ability to provide diagnostic reasoning, clinically relevant explanations, and interactive dialogue, with high performance in subjective ophthalmologist evaluation. These findings suggest that MLLMs may enable accurate, interpretable, and clinically useful image-based diagnosis and classification of AMD.},
}