@article {pmid42363196,
year = {2026},
author = {Pan, M and Sunkara, N and Digbeu, BDE and Gupta, PK},
title = {Baseline visual acuity gaps in age-related macular degeneration: AREDS smokers and non-smokers.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-05035-w},
pmid = {42363196},
issn = {1471-2415},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of blindness in developed countries. Smoking is the only modifiable risk factor and is associated with faster AMD progression. While Age-Related Eye Disease Study (AREDS) supplements are recommended for intermediate AMD, their impact on visual acuity over time remains unclear.

OBJECTIVE: To describe baseline disparities and visual acuity trajectories in patients with intermediate dry AMD stratified by AREDS use and smoking status.

DESIGN: Retrospective observational study of patients with intermediate dry AMD conducted under IRB protocol 22-0267. Data collected from January 1, 2014 to January 1, 2024.

SETTING: Single academic medical center.

PARTICIPANTS: A total of 450 patients (759 eligible eyes) with intermediate dry AMD (ICD code H35.3192) were included. Patients were stratified by smoking status and AREDS use. Participants with fewer than three ophthalmology visits during the 10-year study period were excluded.

EXPOSURE: AREDS supplementation (AREDS1 or AREDS2) and smoking status (current/former vs. never).

MAIN OUTCOMES AND MEASURES: Visual acuity measured in Logarithm of the Minimum Angle of Resolution (LogMAR) at first and final clinic visits. ANOVA, Chi-square tests, and mixed effect regression models were used for analysis. Changes in LogMAR over time were calculated descriptively.

RESULTS: Among 450 patients (mean age, 82.32 years), 255 were smokers (423 eyes) and 195 were non-smokers (336 eyes). Baseline vision was better in non-smokers (mean LogMAR 0.28; SD 0.28) and smokers (mean LogMAR 0.30; SD 0.33) taking AREDS compared to non-smokers (mean LogMAR 0.48; SD 0.44) and smokers (mean LogMAR 0.45; SD 0.47) not taking AREDS (P < 0.0001). All groups experienced visual acuity decline from baseline with no significant differences in final visual acuity among the groups in a mean follow up period of 3.62 years. In a sub-analysis of greater than 5 years follow up mean years of 6.93 ± 1.55 years), a statistically significant difference in final LogMAR values across groups was observed (p = 0.033). The Smokers & AREDS group demonstrated the best final visual acuity (mean 0.39, SD 0.40), followed by Smokers & No-AREDS (mean 0.44, SD 0.43), Non-smokers & AREDS (mean 0.46, SD 0.47), and Non-smokers & No-AREDS (mean 0.72, SD 0.60).

CONCLUSIONS AND RELEVANCE: These results suggest that less than 5 years AREDS users had larger decline in vision from baseline, protective associations of AREDS supplementation may become more discernible over longer follow-up horizons. Real-world observational findings should be interpreted cautiously and do not contradict AREDS efficacy shown in randomized trials.},
}

@article {pmid42363252,
year = {2026},
author = {Sun, X and Dai, H and Chen, Y and Sun, X and Tao, L and Xiao, J and Han, M and Zhao, M and Wang, L and Schulze, A and Schmidt-Ott, UM and Zhao, M and Zhang, X and Wang, Z and Leal, S and Wei, W and , },
title = {Intravitreal aflibercept 8 mg in patients with neovascular age-related macular degeneration from China: 48-week results from the PULSAR trial.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00876-5},
pmid = {42363252},
issn = {2056-9920},
abstract = {BACKGROUND: PULSAR (NCT04423718) was a global, phase 3, randomized, double-masked, non-inferiority study of adults with neovascular age-related macular degeneration (nAMD). Patients were randomized 1:1:1 to receive aflibercept 8 mg every 12 (8q12), or 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following 3 initial monthly doses. This subgroup analysis investigated the efficacy and safety of aflibercept 8 mg vs. aflibercept 2 mg in patients from China with nAMD from the PULSAR trial.

METHODS: This exploratory analysis evaluated the change from baseline in best-corrected visual acuity (BCVA), central retinal thickness (CRT), durability, and safety outcomes through week 48 in patients from China. All results were descriptive in nature.

RESULTS: Least squares (LS) mean (95% confidence interval [CI]) change from baseline in BCVA at week 48 was + 13.2 (+9.0, +17.4), +9.7 (+5.8, +13.7), and + 10.0 (+6.9, +13.1) letters for patients from China in the 8q12 (n = 31), 8q16 (n = 31), and 2q8 (n = 39) groups, respectively. LS mean (95% CI) change from baseline in CRT (µm) at week 48 was -167 (-183, -151), -166 (-195, -137), and -180 (-195, -165) for patients in the 8q12, 8q16, and 2q8 groups, respectively. Randomized dosing intervals were maintained by 88.5% and 73.1% of patients in the 8q12 and 8q16 groups, respectively. The incidence of ocular treatment-emergent adverse events was similar across treatment groups.

CONCLUSIONS: In patients with nAMD from China, aflibercept 8 mg administered over extended dosing intervals demonstrated efficacy and a safety profile consistent with that observed with aflibercept 2 mg, in line with the overall PULSAR cohort.

TRIAL REGISTRATION: ClinicalTrials.gov, TRN NCT04423718. Registration date 8 June 2020.},
}

@article {pmid42363601,
year = {2026},
author = {Kim, J and Min, S and Yum, M and Park, S and Park, S and Shin, D and Park, SW and Park, SY and Do, YJ and Park, JH and Lee, DK},
title = {Cell-penetrating asymmetric siRNA targeting MyD88 suppresses inflammasome-driven ocular degeneration and angiogenesis.},
journal = {Molecular therapy : the journal of the American Society of Gene Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ymthe.2026.06.036},
pmid = {42363601},
issn = {1525-0024},
abstract = {Chronic inflammation mediated by innate immune signaling contributes to retinal degeneration, pathological angiogenesis, and ocular surface damage in age-related macular degeneration (AMD) and dry eye disease (DED). Myeloid differentiation primary response 88 (MyD88), a central adaptor downstream of Toll-like and IL-1 receptors, integrates NF-κB-dependent cytokine induction and inflammasome priming. In this study, we developed OLX10212, a chemically optimized palmitoyl-conjugated, cell-penetrating asymmetric siRNA (cp-asiRNA) that silences MyD88 without an external delivery vehicle. Following intravitreal administration, OLX10212 achieved broad retinal distribution and sustained MyD88 knockdown in mice and rabbits. In sodium iodate- and Alu RNA-induced geographic atrophy models, OLX10212 preserved retinal architecture and electroretinographic function while suppressing NLRP3-associated transcripts, consistent with the inhibition of inflammasome signaling. A single intravitreal dose reduced lesion volume in laser-induced choroidal neovascularization models in mice and cynomolgus monkeys. Vascular endothelial growth factor (VEGF) expression was also decreased in mice, suggesting that OLX10212 modulates pro-angiogenic inflammatory pathways. Topical administration further ameliorated corneal epithelial injury and inflammatory cytokine expression in a benzalkonium chloride-induced DED model. A phase 1 clinical trial of intravitreal OLX10212 in patients with neovascular AMD is ongoing, and phase 2 studies are planned.},
}

@article {pmid42360467,
year = {2026},
author = {Honjo, J and Mukai, R and Itagaki, K and Kato, Y and Tsuchiya, Y and Shioya, T and Tanaka, K and Norikawa, K and Kato, Y and Kasai, A and Sekiryu, T},
title = {Long-term analysis of fibrosis in neovascular age-related macular degeneration: A 7-year follow-up.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42360467},
issn = {1435-702X},
abstract = {PURPOSE: We investigated the 7-year incidence rate of macular fibrosis and its related factors in Japanese patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor therapy.

METHODS: This retrospective study involved 301 eyes of 301 treatment-naïve Japanese patients. Macular fibrosis was diagnosed using color fundus photography and spectral-domain optical coherence tomography. We compared clinical parameters between eyes with and without fibrosis. Fibrosis incidence, lesion morphology, and visual outcomes were assessed across nAMD subtypes. A multivariable logistic regression analysis was performed to identify independent factors associated with fibrosis development.

RESULTS: Fibrosis development was observed in 73 eyes (24.3%). Fibrosis incidence was significantly higher in type 2 macular neovascularization (MNV; 42.1%) than in type 1 MNV (18.1%) and polypoidal choroidal vasculopathy (20.6%). The fibrosis group had significantly worse baseline logarithm of the minimum angle of resolution visual acuity, greater central macular thickness (CMT), and higher incidences of intraretinal fluid (IRF), subretinal hyperreflective material, and retinal hemorrhage than the non-fibrosis group. The most common fibrosis subtype was mixed-type fibrosis, with subretinal fibrosis being more prevalent in type 2 MNV than in type 1 MNV. Visual acuity significantly improved in the non-fibrosis group but not in the fibrosis group. Final visual acuity did not significantly differ across nAMD subtypes in the fibrosis group. In multivariable analysis, worse baseline visual acuity, greater CMT, retinal hemorrhage, IRF, and nAMD subtype were independently associated with fibrosis development.

CONCLUSION: Macular fibrosis occurred across all nAMD subtypes and was associated with poor visual outcomes. Worse baseline visual acuity, greater CMT, retinal hemorrhage, IRF, and nAMD subtype were independently associated with fibrosis development. Thus, baseline disease severity and active exudative lesion characteristics may contribute to fibrotic progression in nAMD.},
}

@article {pmid42361041,
year = {2026},
author = {Ozaki, E and Aktas, S and Mulfaul, K and Brennan, K and Roubeix, C and Palko, S and Robb, K and Ou Yang, TH and Schanne-Klein, MC and Toidze, A and Watson, A and Cahill, M and Westenskow, PD and Feenstra, D and Doyle, SL},
title = {Collagen-producing eye cell atlas reveals distinct fibroblast fates in early injury vs. fibrotic subretinal disease.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {26},
pages = {e2519056123},
doi = {10.1073/pnas.2519056123},
pmid = {42361041},
issn = {1091-6490},
support = {Immunolgy incubator programme//F. Hoffmann-La Roche/ ; SFI 21/SPP/3732//Science Foundation Ireland (SFI)/ ; M2023011//BrightFocus Foundation (BFF)/ ; },
mesh = {Animals ; *Fibroblasts/metabolism/pathology ; Fibrosis/metabolism ; Mice ; *Collagen/metabolism ; *Retina/metabolism/pathology ; Extracellular Matrix/metabolism ; *Macular Degeneration/pathology/metabolism ; Periostin ; Disease Models, Animal ; Collagen Type I/metabolism/genetics ; Humans ; Cell Adhesion Molecules ; },
abstract = {Fibrosis is the end-stage of a maladaptive process that occurs when the body's normal wound-healing strategy becomes dysregulated. Subretinal fibrosis is the end stage of neovascular age-related macular degeneration (nAMD), the most common cause of central vision loss in people over the age of 50. The cellular sources of excess extracellular matrix (ECM) contributing to subretinal fibrosis are unknown, as is the heterogeneity of cells involved in the fibrotic process. Here we identify cells contributing to subretinal fibrosis by using Col1a1-YFP reporter mice to noninvasively image collagen production in real-time in vivo in two disease models, 1) a resolving retinal injury model and 2) a fibrotic model of subretinal disease. We create a collagen-producing eye cell atlas for subretinal injury and demonstrate subretinal fibroblast heterogeneity in healthy, resolving, and fibrotic tissue. We identify distinct molecular characteristics of general repair/resolving fibroblast populations versus pathogenic pro-fibrotic collagen-producing fibroblasts. Integration of this collagen-producing eye cell atlas with a published collagen-producing lung cell atlas shows conserved pro-fibrotic fibroblasts in both organs, yet also uncovers tissue-specific fibroblast populations unique to subretinal fibrosis. A Fap[+]Fgl2[+] fibroblast population significantly expands in subretinal fibrosis that expresses the highest levels of collagens and distinctively expresses ECM components Periostin, Col15a1 and Col6a5. Immunolabeling of mouse and human-donor eye tissue support the fibroblastic expression and perivascular location of periostin as clearly distinguishing between bona fide fibrosis and early disease in nAMD. Our collagen-producing eye cell atlas is a valuable resource for studying distinct fibroblast subsets in homeostasis, early injury, and fibrosis.},
}

Animals
*Fibroblasts/metabolism/pathology
Fibrosis/metabolism
Mice
*Collagen/metabolism
*Retina/metabolism/pathology
Extracellular Matrix/metabolism
*Macular Degeneration/pathology/metabolism
Periostin
Disease Models, Animal
Collagen Type I/metabolism/genetics
Humans
Cell Adhesion Molecules

@article {pmid42362585,
year = {2026},
author = {Chan, KS and Cheng, BT and Banker, MM and Zee, PC and Mirza, RG},
title = {Daylight saving time transition and new-onset retinal vascular disease: a nationwide cohort study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-55281-7},
pmid = {42362585},
issn = {2045-2322},
abstract = {Daylight saving time (DST) transitions lead to disruptions in circadian rhythm, and studies have identified an association between DST transitions and cardiovascular events. Changes in retinal microvasculature can reflect systemic cardiovascular health. This study investigated the relationship between DST transitions and retinal vascular disease. Patients aged 18-64 years old enrolled in the Merative MarketScan Commercial Database between 2012 and 2014 were identified. Incidence of new diagnosis of retinal artery occlusion (RAO), retinal vein occlusion (RVO), proliferative diabetic retinopathy (PDR), and neovascular age-related macular degeneration (nvAMD) were determined after autumn DST transition, spring DST transition, and a summer or winter control period. Survival analysis via Kaplan Meier curves and Cox proportional hazards models were used to determine the effect of variables of interest on new-onset retinal vascular disease during one-week and one-month periods following DST transition. We identified 12,640,343 patients who met inclusion criteria. With a summer control period, there was lower risk of RVO (adjusted hazard ratio [98.75% confidence interval]: 0.84 [0.72-0.99], P = 0.033), and PDR (0.83 [0.73-0.94], P = 0.001) in the month following autumn DST transition. There was higher risk of PDR (1.34 [1.19-1.50], P<0.0001) and nvAMD (1.24 [1.03-1.50], P = 0.015) in the month following spring DST transition. With a winter control period, there was lower risk of RAO (0.75 [0.60-0.94], P = 0.005), RVO (0.66 [0.53-0.82], P<0.0001), PDR (0.61 [0.51-0.72], P<0.0001), and nvAMD (0.64 [0.49-0.83], P < 0.0001) in the month following autumn DST transition. Further investigation into the effects of circadian disruption on ocular health is warranted.},
}

@article {pmid42362987,
year = {2026},
author = {Sun, G and Zeraatkar, D and Man, REK and Sivaprasad, S and Borrelli, E and Steel, DH and Guymer, RH and Wong, TY and Wykoff, CC and Ma, J and Chaudhary, V},
title = {Vision-related quality of life in non-neovascular age-related macular degeneration: a protocol for systematic review and meta-analysis.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42362987},
issn = {1476-5454},
abstract = {Age-related macular degeneration (AMD) is a progressive retinal disease and a major cause of visual impairment in older adults. Non-neovascular AMD (non-nAMD), the more common phenotype, can substantially impair vision-related quality of life (QoL) even when visual acuity remains relatively preserved. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) is the most widely used instrument for assessing vision-related QoL in AMD. However, QoL in non-nAMD has not been systematically synthesised across disease stages and settings. This review aims to summarise vision-related QoL in treatment-naive patients with non-nAMD, examine how QoL varies by disease stage and measurement instrument and identify study-level factors associated with QoL differences. We will search MEDLINE, Embase, EBM Reviews and APA PsycINFO from inception for original studies reporting mean values or mean differences, with corresponding variability, for overall or subscale scores from the NEI-VFQ-25 or other validated vision-related QoL instruments. Two reviewers will independently screen studies, extract data and assess risk of bias using the appropriate Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Random-effects meta-analyses will be conducted to pool NEI-VFQ-25 composite and subscale scores by non-nAMD stage and, where available, to estimate differences between stages or versus controls. Instrument-specific meta-analyses will be performed for other QoL measures when feasible and standardised metrics will be used to combine instruments assessing similar constructs but using different scales. Meta-regression will explore whether QoL varies with study-level characteristics. The findings will clarify the functional burden of non-nAMD and support future clinical research and trial design.},
}

@article {pmid42346801,
year = {2026},
author = {Shad, HH and Dörschmann, P and Hautmann, SL and Roider, J and Klettner, A},
title = {Marine-Derived Fucoidan Modulates Pathways Associated with Age-Related Macular Degeneration in Cellular and Zebrafish Models.},
journal = {Marine drugs},
volume = {24},
number = {6},
pages = {},
pmid = {42346801},
issn = {1660-3397},
mesh = {Animals ; *Polysaccharides/pharmacology ; Zebrafish ; Retinal Pigment Epithelium/drug effects/metabolism ; *Macular Degeneration/drug therapy/metabolism ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; Oxidative Stress/drug effects ; Swine ; Anti-Inflammatory Agents/pharmacology ; Cytokines/metabolism ; Vascular Endothelial Growth Factor A/metabolism ; Antioxidants/pharmacology ; },
abstract = {Fucoidan, a sulfated polysaccharide, is known for its beneficial bioactive effects, for example antioxidant, anti-inflammatory, and vascular modulatory effects. Such a bioactive compound may also be useful for treating neurodegenerative diseases like age-related macular degeneration (AMD). Our research focuses on AMD-related pathomechanisms using primary porcine retinal pigment epithelium (RPE) cells in vitro and zebrafish (Danio rerio) models in vivo. We tested the bioactivity of a commercially available fucoidan (FVs) from bladderwrack with regard to pathomechanisms of AMD. We performed multiplex assays, RT-qPCR and fluorescence-based assays for the formation of nitric oxide (DAF-FM assay) and reactive oxygen species (DCF-DA assay) to analyze angiogenesis-related chemokines and pro-inflammatory cytokines as well as protection against oxidative stress and inflammatory insult. Our results showed that FVs significantly reduced the secretion of pro-angiogenic vascular endothelial growth factor A (VEGF-A) and follistatin as well as the pro-inflammatory cytokines interleukin 8 (IL-8) after lipopolysaccharide (LPS) and polyinosinic/polycytidylic acid (PIC) induction. Interleukin 6 (IL-6) was also reduced in the supernatant of the RPE cells. Additionally, in zebrafish, fucoidan decreased the production of NO and ROS. Gene expression of zebrafish embryos revealed anti-inflammatory effects by suppressing pro-inflammatory genes and significantly downregulating, e.g., interleukin 1 beta (IL-1β). These findings indicate modulation of oxidative stress, inflammatory responses, and VEGF secretion of the used FVs. This study demonstrates that fucoidan possesses AMD-relevant bioactivities in vitro and in vivo, suggesting fucoidan warrants further investigation in AMD-related research and related pathological mechanisms.},
}

Animals
*Polysaccharides/pharmacology
Zebrafish
Retinal Pigment Epithelium/drug effects/metabolism
*Macular Degeneration/drug therapy/metabolism
Reactive Oxygen Species/metabolism
Disease Models, Animal
Oxidative Stress/drug effects
Swine
Anti-Inflammatory Agents/pharmacology
Cytokines/metabolism
Vascular Endothelial Growth Factor A/metabolism
Antioxidants/pharmacology

@article {pmid42347571,
year = {2026},
author = {Tlaiss, Y and Warrak, J and Warrak, E},
title = {Ultra-Early OCT Changes After Intravitreal Injection: Evidence Consistent with Transient Mechanical Compression.},
journal = {Vision (Basel, Switzerland)},
volume = {10},
number = {2},
pages = {},
doi = {10.3390/vision10020035},
pmid = {42347571},
issn = {2411-5150},
abstract = {(1) Background: Ultra-early optical coherence tomography (OCT) changes following intravitreal injection may reflect transient mechanical compression rather than pharmacologic effects; however, this temporal profile has not been rigorously characterised with appropriate statistical methodology. (2) Methods: In this prospective observational study, 40 eyes of 40 consecutive patients (one per patient) with macular edema secondary to neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), or chronic central serous retinopathy (CSR) underwent intravitreal bevacizumab (n = 35) or triamcinolone acetonide (n = 5). Goldmann applanation tonometry and spectral-domain OCT were performed at baseline, 2-5 min, 15 ± 5 min, 24 h, and 48 h post-injection. Repeated-measures ANOVA with Greenhouse-Geisser correction, linear regression, and Spearman rank correlation were applied. (3) Results: Central subfield thickness (CST) decreased markedly at 15 ± 5 min (mean -24.8 ± 11.5%; 95% CI: -28.5% to -21.1%; p < 0.001; partial η[2] = 0.70), with near-complete rebound by 48 h (-1.0%; p = 0.400). Peak intraocular pressure (IOP) elevation correlated with CST reduction (Spearman rs = 0.61; 95% CI: 0.39-0.77; p < 0.001), and baseline CST predicted thinning magnitude (R[2] = 0.52; p < 0.001). (4) Conclusions: Ultra-early OCT thinning after intravitreal injection is consistent with transient mechanical compression. Retinal thickness measurements within 48 h post-injection should be interpreted with caution when assessing treatment response, as early anatomic reduction may not reflect pharmacologic efficacy.},
}

@article {pmid42347990,
year = {2026},
author = {Borrelli, E and Neri, G and Berni, A and Olivieri, C and Chhablani, J and Corradetti, G and Dolz-Marco, R and Reiter, GS and Zur, D and Bandello, F and Reibaldi, M},
title = {Review of emerging imaging findings to reveal a broader spectrum of lesions in AMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42347990},
issn = {1435-702X},
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in developed countries, with prevalence expected to reach nearly 288 million by 2040. Accurate classification of AMD is critical for patient care and clinical research, guiding prognosis, therapeutic strategies, and the design of clinical trials. A widely adopted framework, the Beckman classification, stratifies AMD based primarily on color fundus photography (CFP) findings, defining stages from early to late disease. While simple and clinically applicable, such systems do not account for several key phenotypes revealed by advances in multimodal imaging. Such novel phenotypes include reticular pseudodrusen (RPD), acquired vitelliform lesions (AVL), non-exudative macular neovascularization (MNV), incomplete retinal pigment epithelium and outer retina atrophy (iRORA), and non-neovascular exudative fluid. Recent imaging modalities-including optical coherence tomography (OCT), fundus autofluorescence (FAF), and OCT angiography (OCTA)-have uncovered features with important prognostic implications that are currently misclassified with respect to AMD. For example, eyes with RPD or AVL in the absence of drusen are currently misclassified as "early AMD" or excluded altogether, despite their high risk of progression. Similarly, the ambiguous status of non-exudative MNV, which carries both protective and harmful potential, highlights the need for greater granularity. The Classification of Atrophy Meetings (CAM) group has also introduced refined OCT-based definitions such as iRORA and cRORA, underscoring early degenerative changes that precede geographic atrophy. Moreover, novel entities like non-neovascular intraretinal or subretinal fluid challenge the assumption that exudation is synonymous with neovascular AMD. This review synthesizes recent evidence highlighting the limitations of current classification systems in light of these advances. Furthermore, we emphasize that intermediate AMD, currently treated as a uniform category, actually encompasses highly heterogeneous phenotypes with distinct risks and trajectories. A more nuanced, imaging-integrated classification system is urgently needed to improve disease staging, identify high-risk eyes, and ensure appropriate patient selection for emerging therapies. Such a framework would not only better reflect the complex natural history of AMD but also facilitate the regulatory shift toward continuous, quantitative endpoints in clinical trials.},
}

@article {pmid42348183,
year = {2026},
author = {Wakefield, ZR and Reddy, AK and Wang, SY},
title = {Loneliness, Blindness, and Major Eye Disease.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.2168},
pmid = {42348183},
issn = {2168-6173},
}

@article {pmid42350446,
year = {2026},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX},
title = {Localized interdigitation zone thinning in age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-57489-z},
pmid = {42350446},
issn = {2045-2322},
abstract = {To assess prevalence and associations of localized thinnings of the interdigitation zone ("IZT") without adjacent drusen or reticular pseudodrusen in a general population, affected by age-related macular degeneration (AMD), or free of any other retinal disease. On optical coherence tomographic images, taken from the macula of participants of the population-based Beijing Eye Study, we searched for IZTs. The study population included 1271 eyes (mean age:64.7 ± 9.8 years; range:50-91 years). IZT prevalence increased from 2/442 (0.5%;95%CI:0.0,1.0) in the normal group to 49/543 (9.0%;95%CI:7.0,11.0), 90/275 (32.7%;95%CI:27.2,38.2), and 9/11 (81.8%;95%CI:55.0,100) in eyes with early, intermediate or late AMD (geographic atrophy), respectively. IZTs were spatially associated with ellipsoid zone (EZ) defects (114/150 (76.0%) eyes), external limiting membrane (ELM) defects (92/150 (61.3%) eyes), any intraretinal hyperreflective foci (iHRF) (143/150 (95.2%) eyes), iHRFs in the outer nuclear layer or beyond (111/150 (74.0%) eyes), macular hypopigmentation (76/150 (50.7%) eyes), and RPE hypertransmission (46/150 (30.7%) eyes), in addition to a non-spatial association with a higher prevalence of outer nuclear layer thinning (48/150 (32.0%) eyes). Higher IZT prevalence correlated (multivariable analysis) with higher AMD stage (OR:1.28;95%CI:1.08,1.51;P = 0.004), and higher prevalences of EZ defects (OR:7.97;95%CI:4.20,15.1;P < 0.001), iHRFs with a smoke-like appearance in the outer nuclear layer (OR:2.52;95%CI:1.32,4.82;P = 0.005), RPE hypertransmissions (OR:12.6;95%CI:2.92,54.7;P < 0.001), and outer nuclear layer thinning (OR:27.5;95%CI:6.12,123;P < 0.001). IZTs are a common feature of AMD including the early AMD stage. Their spatial association with defects in the overlying EZ, IHRFs and macular hypopigmentations may warrant further research of a potential involvement of an intraretinal RPE cell migration in the IZT etiology.},
}

@article {pmid42350598,
year = {2026},
author = {Çelenk, E and Torun, IM},
title = {Evaluating the educational quality and reliability of YouTube videos on red light therapy for eye diseases.},
journal = {Lasers in medical science},
volume = {41},
number = {1},
pages = {},
pmid = {42350598},
issn = {1435-604X},
mesh = {Humans ; *Eye Diseases/therapy ; *Social Media ; *Video Recording/standards ; Red Light ; Reproducibility of Results ; *Ophthalmology/education ; *Patient Education as Topic ; },
abstract = {To investigate the use of YouTube videos as an educational and informational resource regarding the use of red light therapy in eye diseases. On May 1, 2025, a comprehensive search was conducted on the YouTube platform (https://www.youtube.com) using the keywords "Red light therapy in eye disease" and "Use of red light therapy in eye diseases for patient information". Videos under 60 s in duration, those lacking audio, duplicate entries, irrelevant content, and videos with disabled comment sections were excluded from the analysis. These exclusion criteria were predefined prior to data collection. Following video selection (E.Ç., M.T.), all videos were independently evaluated by two ophthalmologists, and statistical analyses were performed using the finalized dataset. Parameters assessed included total views, number of comments, likes, time elapsed since upload, video duration, view rate, interaction index, video source, and content characteristics. In addition, videos were categorized according to quality level based on Global Quality Score (GQS) scores as low-to-moderate quality (GQS < 4) and high quality (GQS ≥ 4). Comparisons were then performed according to quality category with respect to uploader source, video purpose, and engagement-related parameters. Out of 110 YouTube videos reviewed, 53 were excluded based on predefined criteria. The remaining 57 videos covered myopia (22.8%), dry eye (33.3%), diabetic retinopathy (12.3%), and age-related macular degeneration (31.6%). Inter-rater agreement was high (mDISCERN ICC: 0.952; JAMA ICC: 0.923; GQS ICC: 0.890). Videos uploaded by physicians had significantly higher mDISCERN, JAMA, and GQS scores. Educational videos had higher mDISCERN and JAMA scores than patient-information videos. A moderate positive correlation was found between the number of likes and the interaction index (r = 0.458, p < 0.01). The interaction index was not significantly associated with mDISCERN, JAMA, or GQS scores, indicating that engagement metrics were not reliable indicators of informational quality. Among disease categories, age-related macular degeneration videos had the highest mean quality scores, although the differences were not statistically significant. Most videos were classified as low-to-moderate quality (82.5%), while 17.5% were classified as high quality. High-quality videos had significantly higher view counts and like counts than low-to-moderate quality videos. The overall quality and formal reliability of YouTube videos on red light therapy in ophthalmology were low to moderate. Physician-uploaded and educational videos provided higher-quality information. Although high-quality videos showed greater engagement, popularity metrics were not reliable indicators of informational quality. More evidence-based and accessible video content is needed to support patient education.},
}

Humans
*Eye Diseases/therapy
*Social Media
*Video Recording/standards
Red Light
Reproducibility of Results
*Ophthalmology/education
*Patient Education as Topic

@article {pmid42351411,
year = {2026},
author = {Sharifzadeh, M},
title = {Melanin Correction Is Essential for Quantitative Autofluorescence-Based Measurement of Macular Pigment.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {12},
pages = {},
doi = {10.3390/diagnostics16121751},
pmid = {42351411},
issn = {2075-4418},
abstract = {Macular pigment optical density (MPOD) is widely measured by dual-wavelength autofluorescence imaging (AFI) because the method is noninvasive, image-based, and clinically practical. AFI-derived MPOD and macular pigment optical volume (MPOV) are increasingly used as retinal biomarkers in clinical research, supplementation studies, disease-risk interpretation, and population-based comparisons. However, conventional dual-wavelength AFI assumes that posterior absorbers other than macular pigment (MP), particularly melanin, are negligible or sufficiently stable not to bias the measurement. This assumption may limit the diagnostic and biomarker reliability of AFI-derived MP metrics. This manuscript presents a focused biological, optical, and mathematical analysis of AFI-based MP quantification. The foundational AFI literature, the melanin imaging literature, retinal pigment epithelium (RPE) pigment biology, and related optical modeling concepts were examined to evaluate where melanin enters the AFI signal pathway, how it may confound MPOD and MPOV, and how a melanin-sensitive baseline could improve quantitative specificity within the AFI domain. Conventional dual-wavelength AFI estimates MP indirectly from attenuation of RPE lipofuscin autofluorescence under excitation wavelengths that differ in MP absorption. Because melanin is located in the RPE and choroid, varies with retinal location, age, and pigmentation, and can influence the same excitation and detection pathway, unmeasured melanin can become embedded in the apparent MPOD signal. Under these conditions, reported MPOD and derived MPOV are better understood as model-dependent estimates whose quantitative specificity may vary across subjects, retinal locations, devices, and studies. This has direct implications for diagnostic interpretation, normative databases, cross-subject comparison, supplementation-response studies, and biomarker-based retinal assessment. Melanin correction is not a minor refinement of AFI-based MP quantification. It is likely necessary when AFI-derived MP metrics are intended to be interpreted as quantitatively specific retinal biomarkers rather than conditionally approximate optical estimates. A melanin-corrected AFI framework, based on introducing a melanin-sensitive baseline wavelength outside the principal MP absorption range, offers a path toward more reliable MPOD and MPOV interpretation in clinical, diagnostic, and supplementation-related studies.},
}

@article {pmid42351718,
year = {2026},
author = {Tîrziu, AT and Romanescu, M and Ciordas, PD and Mercea, N and Munteanu, M and Horhat, FG and Chis, AR and Preda, MA},
title = {Metagenomic Profiling of the Gut Microbiome in Age-Related Macular Degeneration-A Pilot Study.},
journal = {Biomedicines},
volume = {14},
number = {6},
pages = {},
doi = {10.3390/biomedicines14061290},
pmid = {42351718},
issn = {2227-9059},
support = {CNFIS-FDI-2024-F-0451//Consiliul National pentru Finantarea Invatamantului Superior/ ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a multifactorial retinal disease involving inflammatory, metabolic, and genetic factors. Increasing evidence suggests that the gut microbiome may contribute to systemic pathways involved in retinal homeostasis. This exploratory pilot study investigated gut microbiome alterations in AMD patients and controls using long-read whole-genome sequencing. Methods: Bacterial DNA was extracted from fecal samples and analyzed using Oxford Nanopore sequencing, followed by taxonomic profiling, alpha and beta diversity analyses, and differential abundance testing. Results: AMD patients showed significantly reduced microbial diversity, reflected by lower richness, Shannon and Simpson indices. Species-level beta diversity analyses revealed significant differences in microbial community composition, particularly with Bray-Curtis metrics, alongside increased inter-individual microbial heterogeneity in AMD samples. Differential abundance analyses identified the depletion of several potentially beneficial commensal taxa, including Faecalibacterium prausnitzii and Parabacteriodes distasonis, whereas Staphylococcus aureus was enriched in AMD patients. Comparisons between wet and dry subtypes showed no significant differences in alpha or beta diversity. Conclusions: Overall, the findings support the presence of gut microbial dysbiosis in AMD characterized by reduced diversity, abundance-driven community shifts, and increased microbiome heterogeneity. Given the small cohort size, cross-sectional design and lack of functional analysis, these results should be considered preliminary and hypothesis-generating.},
}

@article {pmid42351905,
year = {2026},
author = {Mohanty, S and Batabyal, S and Kim, S and Carlson, M and Dibas, A},
title = {Therapeutic Efficacy of Multi-Characteristic Opsin Gene Therapy in a Mouse Model of Stargardt Disease.},
journal = {Bioengineering (Basel, Switzerland)},
volume = {13},
number = {6},
pages = {},
doi = {10.3390/bioengineering13060660},
pmid = {42351905},
issn = {2306-5354},
support = {R44EY025905/EY/NEI NIH HHS/United States ; },
abstract = {Optogenetic gene therapy-based treatment offers a unique approach to bypass dysfunctional or degenerated photoreceptors in retinal degenerative disorders. Ambient light-activatable multi-characteristic opsin (MCO) targeted to bipolar cells of the retina has demonstrated partial vision restoration in animal models of retinitis pigmentosa (RP). Here, we describe the potential therapeutic efficacy of intravitreally delivered AAV-carried MCO-010 in a mouse model of Stargardt disease. MCO-010 treatment led to significantly improved behavioral outcomes in the visually guided radial arm water maze. Furthermore, longitudinal optical coherence tomographic imaging showed that the MCO-010 treatment led to no notable change in the retina thickness. Furthermore, the MCO-010-treated mice exhibited higher electrophysiological responses compared to the control group. Together, these findings demonstrate potential vision-restoring and disease-modifying aspects of ambient light-activatable intravitreal MCO-010 therapy.},
}

@article {pmid42352019,
year = {2026},
author = {Yang, Y and Deng, Y and Li, X and Zhou, P and Peng, Q and Ratnayaka, JA},
title = {Epigenetic-Mitochondrial-Metabolic Crosstalk in Retinal Pigment Epithelium (RPE) Dysfunction in Age-Related Macular Degeneration (AMD).},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/antiox15060713},
pmid = {42352019},
issn = {2076-3921},
support = {82274341//National Natural Science Foundation of China/ ; 2024JJ5304, 2025JJ60633//Natural Science Foundation of Hunan Province/ ; 2024JK2122//Key Research and Development Program of Hunan Province/ ; 23A0278, 23B0346//Scientific research project of Hunan Provincial Department of Education/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults and is characterized by progressive dysfunction of the retinal pigment epithelium (RPE). Although genetic susceptibility and environmental exposure both contribute to disease risk, the mechanisms through which chronic metabolic and oxidative stress are integrated into sustained RPE dysfunction remain incompletely understood. Increasing evidence from human AMD donor tissue and experimental RPE models indicates that epigenetic regulation operates at the interface between mitochondrial dysfunction, redox imbalance, and transcriptional remodeling. This review synthesizes current findings on DNA methylation, chromatin accessibility, histone modification, and RNA-based regulation in AMD, with emphasis on their metabolic and mitochondrial context. Studies in human AMD-RPE demonstrate that epigenetic alterations are generally selective rather than global and frequently involve pathways related to mitochondrial maintenance, lipid metabolism, oxidative stress responses, and cellular homeostasis. Mechanistically, mitochondrial dysfunction and reactive oxygen species (ROS) may influence epigenetic regulation through altered Nicotinamide adenine dinucleotide (NAD[+]) availability, acetyl-CoA metabolism, redox-sensitive chromatin regulation, and modulation of DNA methyltransferase and histone deacetylase activity. Redox-sensitive pathways, including antioxidant signaling, further connect mitochondrial stress to adaptive or maladaptive transcriptional responses in the RPE. Importantly, while several interactions discussed are supported by findings in human AMD tissue, other components of the proposed epigenetic-mitochondrial-redox framework remain inferential or model-based and require further validation. Rather than acting as isolated disease triggers, epigenetic changes are more likely to function as stress-responsive regulatory layers that stabilize transcriptional states over time in a long-lived post-mitotic tissue. We further discuss unresolved questions regarding causality, reversibility, therapeutic feasibility, and stage-specific intervention strategies. Collectively, this framework positions the epigenetic-mitochondrial-redox axis as a unifying model for understanding RPE vulnerability and AMD progression.},
}

@article {pmid42352071,
year = {2026},
author = {Chen, TC and Vo, TL and Tsou, SC and Wang, HD and Wang, I and Chuang, CJ and Lin, HW and Chang, YY},
title = {Tetrahydrocurcumin Attenuates NaIO3-Induced Retinal Oxidative Injury via Suppression of NOX2-Derived ROS-Mediated Apoptosis.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {6},
pages = {},
doi = {10.3390/antiox15060765},
pmid = {42352071},
issn = {2076-3921},
support = {MOST 111-2320-B-040 -006 -MY3//National Science and Technology Council/ ; },
abstract = {Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of reactive oxygen species (ROS); however, its mechanistic role in sodium iodate (NaIO3)-induced oxidative injury remains unclear. Tetrahydrocurcumin (THC), the major metabolite of curcumin, exhibits potent antioxidant and cytoprotective activities, but its protective effects against AMD-associated retinal degeneration have not been fully elucidated. In the present study, we investigated whether THC protects against NaIO3-induced ROS-mediated apoptosis in RPE cells through regulation of NOX2 signaling. In vitro, THC significantly attenuated NaIO3-induced cytotoxicity and prevented apoptosis by suppressing hydrogen peroxide (H2O2) production and intracellular ROS accumulation in ARPE-19 cells. THC also preserved mitochondrial membrane potential by inhibiting the Src/p47[phox]/NOX2 signaling pathway and subsequently attenuated mitochondria-mediated apoptotic signaling. Furthermore, THC markedly reduced the expression of apoptotic proteins, including Bax, cleaved caspase-3, and cleaved PARP, concomitantly with suppression of Ras/Raf/MEK/ERK signaling. Mechanistically, treatment with the selective NOX2 inhibitor GSK2795039 significantly attenuated NaIO3-induced ROS accumulation and mitochondrial depolarization, while co-treatment with THC further enhanced these protective effects. In vivo, THC ameliorated NaIO3-induced retinal structural abnormalities by preserving the outer nuclear layer (ONL), reducing caspase-3 expression, and improving pupillary light responses in mice. Collectively, these findings demonstrate that THC protects against NaIO3-induced retinal degeneration through suppressing NOX2-dependent oxidative stress and downstream Ras/Raf/MEK/ERK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for AMD and other oxidative stress-related retinal disorders.},
}

@article {pmid42352232,
year = {2026},
author = {Ding, S and Li, J and Chen, Z and Bai, W and Li, K},
title = {Calcium at the Helm: Mechanisms and Therapeutic Targets in the Retinal Neurovascular Unit.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060763},
pmid = {42352232},
issn = {2218-273X},
support = {82571232//National Natural Science Foundation of China/ ; BK20240122//Natural Science Foundation of Jiangsu Province/ ; },
mesh = {Humans ; Animals ; *Calcium/metabolism ; Diabetic Retinopathy/metabolism/drug therapy/pathology ; *Retina/metabolism/drug effects/pathology ; Glaucoma/metabolism/drug therapy/pathology ; Blood-Retinal Barrier/metabolism ; *Retinal Diseases/metabolism/drug therapy ; Calcium Channel Blockers/pharmacology/therapeutic use ; Retinal Ganglion Cells/metabolism/pathology ; },
abstract = {Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia-reperfusion (RIR) injury, and Alzheimer's disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood-retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β-driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders.},
}

Humans
Animals
*Calcium/metabolism
Diabetic Retinopathy/metabolism/drug therapy/pathology
*Retina/metabolism/drug effects/pathology
Glaucoma/metabolism/drug therapy/pathology
Blood-Retinal Barrier/metabolism
*Retinal Diseases/metabolism/drug therapy
Calcium Channel Blockers/pharmacology/therapeutic use
Retinal Ganglion Cells/metabolism/pathology

@article {pmid42352349,
year = {2026},
author = {Konukcu, O and Argun, M and Acer, S and Çelik, Ö and Tök, Ö and Tök, L and Nazıroğlu, M},
title = {An In Vitro Evaluation of a New Approach in AMD: Effects of the Combination of Resveratrol and Anti-VEGFs on ARPE-19 Cells.},
journal = {Biomolecules},
volume = {16},
number = {6},
pages = {},
doi = {10.3390/biom16060883},
pmid = {42352349},
issn = {2218-273X},
support = {SDU-BAP, Project No: TTU-2020-8124//Süleyman Demirel University/ ; },
mesh = {Humans ; *Resveratrol/pharmacology ; *Macular Degeneration/drug therapy/metabolism/pathology ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism ; Apoptosis/drug effects ; Cell Line ; Cell Survival/drug effects ; *Ranibizumab/pharmacology ; Oxidative Stress/drug effects ; *Recombinant Fusion Proteins/pharmacology ; Receptors, Vascular Endothelial Growth Factor ; Reactive Oxygen Species/metabolism ; Retinal Pigment Epithelium/drug effects/metabolism ; Antioxidants/pharmacology ; Mitochondria/drug effects/metabolism ; Angiogenesis Inhibitors/pharmacology ; },
abstract = {Anti-vascular endothelial growth factor agents (anti-VEGFs) are the cornerstone of treatment for neovascular age-related macular degeneration (AMD). Resveratrol is a natural polyphenol with well-established antioxidant and anti-apoptotic properties. This study investigated whether resveratrol exerts cytoprotective effects when combined with anti-VEGFs on ARPE-19 cells in vitro. Cells were treated with ranibizumab (RNZ), aflibercept (AFL), or ziv-aflibercept (ZFL), either alone or in combination with resveratrol. Mitochondrial and cytosolic reactive oxygen species (MitROS and CytROS), mitochondrial membrane depolarization (MitDep), caspase-3, -8 and -9 activities, cell viability, apoptosis, and VEGF-A levels were evaluated using confocal microscopy, plate reader-based assays, and ELISA techniques. Anti-VEGFs induced tolerable oxidative or apoptotic stress in ARPE-19 cells but did not exhibit intrinsic antioxidant and cytoprotective effects. The addition of resveratrol significantly enhanced beneficial effects by reducing oxidative stress, preserving mitochondrial integrity, and suppressing intrinsic apoptotic signalling, while increasing cell viability. VEGF-A levels were effectively reduced by anti-VEGF treatment, and this suppression was further augmented by resveratrol without compromising cellular survival. These findings indicate that resveratrol acts as an additive modulator that strengthens the cellular effects of anti-VEGFs on ARPE-19 cells. The combination strategy may represent a supportive approach to optimize long-term anti-VEGF therapy in AMD.},
}

Humans
*Resveratrol/pharmacology
*Macular Degeneration/drug therapy/metabolism/pathology
*Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
Apoptosis/drug effects
Cell Line
Cell Survival/drug effects
*Ranibizumab/pharmacology
Oxidative Stress/drug effects
*Recombinant Fusion Proteins/pharmacology
Receptors, Vascular Endothelial Growth Factor
Reactive Oxygen Species/metabolism
Retinal Pigment Epithelium/drug effects/metabolism
Antioxidants/pharmacology
Mitochondria/drug effects/metabolism
Angiogenesis Inhibitors/pharmacology

@article {pmid42353616,
year = {2026},
author = {Menna, F and Lupo, S and De Luca, L and Baldascino, A and Vingolo, EM and Meduri, A},
title = {Mitochondrial Dysfunction and Oxidative Stress in Retinal Degeneration: Mechanisms, Biomarkers, and Therapeutic Perspectives.},
journal = {Current issues in molecular biology},
volume = {48},
number = {6},
pages = {},
doi = {10.3390/cimb48060612},
pmid = {42353616},
issn = {1467-3045},
abstract = {Mitochondrial dysfunction and oxidative stress are increasingly recognized as key contributors to the development and progression of retinal degenerative diseases, including age-related macular degeneration and inherited retinal dystrophies. Growing evidence suggests that alterations in mitochondrial function, excessive production of reactive oxygen species, defective mitophagy, and chronic inflammatory responses are closely interconnected processes that contribute to retinal cell damage and degeneration. This review provides an overview of the current understanding of the molecular mechanisms linking mitochondrial dysfunction to retinal degeneration, with particular emphasis on the impact of oxidative stress, mitochondrial quality-control pathways, and inflammatory signaling. Available evidence indicates that mitochondrial DNA damage, impaired bioenergetics, and dysregulated mitochondrial dynamics play a crucial role in the degeneration of photoreceptors and retinal pigment epithelium cells. In turn, oxidative stress further exacerbates mitochondrial impairment, creating a self-sustaining cycle that promotes disease progression. Recent advances have also highlighted the therapeutic potential of targeting mitochondrial pathways. Although several mitochondria-directed strategies have shown encouraging results in experimental models, their translation into clinical practice remains at an early stage. Overall, the available data identify mitochondria as a promising therapeutic target and support the development of precision medicine approaches aimed at preserving retinal function and slowing disease progression in patients with retinal degenerative disorders.},
}

@article {pmid42355765,
year = {2026},
author = {Bousamri, A and Kana'an, M and Alharbi, F and Alqudah, N},
title = {Real-World Outcomes of Switching to Aflibercept 8 mg in Previously Treated Neovascular Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis.},
journal = {Journal of clinical medicine},
volume = {15},
number = {12},
pages = {},
doi = {10.3390/jcm15124599},
pmid = {42355765},
issn = {2077-0383},
abstract = {Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung-Knapp-Sidik-Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: -0.017 logMAR; 95% CI: -0.027 to -0.007; +0.83 ETDRS letters; I[2] = 0%). CST decreased significantly (WMD: -21.5 µm; 95% CI: -29.3 to -13.7; I[2] = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I[2] = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes.},
}

@article {pmid42356258,
year = {2026},
author = {Szulim, D and Kucharska, E and Machalińska, A and Kuprjanowicz, L and Czupryński, P and Szczuko, M},
title = {Impact of an Individualized Dietary Intervention on Body Composition and Clinical Outcomes in Patients with Neovascular Age-Related Macular Degeneration: A Pilot Study.},
journal = {Nutrients},
volume = {18},
number = {12},
pages = {},
doi = {10.3390/nu18121870},
pmid = {42356258},
issn = {2072-6643},
mesh = {Humans ; Pilot Projects ; Female ; *Body Composition ; Male ; Prospective Studies ; Aged ; *Macular Degeneration/diet therapy/physiopathology ; Treatment Outcome ; Aged, 80 and over ; },
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of permanent deterioration of central vision in elderly people. While anti-VEGF therapy remains the standard of care for neovascular AMD, disease progression and functional deterioration remain common. Methods: This pilot prospective controlled study evaluated the effects of an individualized dietary intervention in patients with neovascular AMD receiving anti-VEGF therapy. A total of 43 patients completed a six-month follow-up and were divided into a control group (standard treatment) and an intervention group receiving a personalized dietary plan. Anthropometric and body composition parameters were assessed using bioelectrical impedance analysis (BIA). Clinical retinal outcomes were classified as improvement, no change, or deterioration. Statistical analyses included parametric and non-parametric tests. Results: Retinal outcomes did not differ significantly between groups, although patients with retinal improvement or stabilization in the intervention group tended to exhibit more favorable changes in body composition. After adjustment for baseline values using analysis of covariance (ANCOVA), the dietary intervention remained significantly associated with reductions in body weight and BMI (p < 0.01). After 6 months, the intervention group demonstrated a numerically higher frequency of retinal improvement and a lower frequency of retinal deterioration compared with the control group; however, these differences were not statistically significant (p = 0.386). Conclusions: An individualized dietary intervention effectively improved body composition in patients with neovascular AMD but did not produce a statistically significant effect on retinal status over six months. Nevertheless, the dietary intervention group showed numerically more favorable retinal outcomes than the control group. Dietary modification may support general health and weight management.},
}

Humans
Pilot Projects
Female
*Body Composition
Male
Prospective Studies
Aged
*Macular Degeneration/diet therapy/physiopathology
Treatment Outcome
Aged, 80 and over

@article {pmid42356301,
year = {2026},
author = {Kalu, KA and McMonnies, C and Lin, S and Arcot, J},
title = {The Relative Bioavailability of Lutein and Zeaxanthin in the Presence of Omega-3 Supplements and Their Effect on Oxidative Stress Levels in Humans: A Pilot Study.},
journal = {Nutrients},
volume = {18},
number = {12},
pages = {},
doi = {10.3390/nu18121914},
pmid = {42356301},
issn = {2072-6643},
mesh = {Humans ; *Lutein/pharmacokinetics/blood/administration & dosage ; *Zeaxanthins/pharmacokinetics/blood/administration & dosage ; Pilot Projects ; Male ; *Dietary Supplements ; Female ; *Fatty Acids, Omega-3/administration & dosage/pharmacology ; Biological Availability ; *Oxidative Stress/drug effects ; Adult ; },
abstract = {Introduction: Lutein+Zeaxanthin (L+Z) are the major constituents of macular pigments of the retina. There is a lack of information on the bioavailability of the two compounds in the presence and absence of omega-3 fatty acids in L+Z supplements which are commonly prescribed to treat macular degeneration. Despite growing interest in L+Z supplementation, there remains a limited understanding of their short-term bioavailability dynamics and the potential added value of omega-3 co-supplementation. This pilot study reports on the bioavailability of serum responses to L+Z supplements in the presence of omega-3 fatty acids and evaluates time-resolved analytical approaches using Area Under the Curve. Subjects/Methods: A total of 10 men and six women with an average age of 31.38 ± 1.27 years participated in this randomised, non-blinded, controlled study for a total of 19 days (7-day wash-out period plus 12-day intervention period). The control group (n = 9) consumed the L+Z supplement (12 mg/d) only, while the intervention group (n = 7) consumed the L+Z supplement along with 900 mg/d of an omega-3 supplement (540 mg EPA + DHA 360 mg). Each group adhered to a comprehensive low-carotenoid and omega-3 diet list (LCOD) for the 7-day wash-out period and the 12-day intervention period. The participants reported the foods they consumed daily in their diet logbooks, online logs, and the ASA 24 diet assessment log over the study period. The body composition of each subject in the two groups was assessed before and after the study using a SECA body composition analyser, and the relative serum L+Z response in both groups was determined using Area Under the Curve (AUC and incremental AUC) by trapezoidal approximation. Results: The mean ± SEM baseline serum lutein+zeaxanthin (L+Z) concentrations measured at the end of the wash-out period (Day 7) were 2.23 ± 0.65 µg/mL in the control group and 1.20 ± 0.53 µg/mL in the intervention group. Following wash-out, serum L+Z concentrations increased in both groups, reaching 2.81 ± 0.90 µg/mL (control) and 2.63 ± 1.21 µg/mL (intervention) at Day 13, and 2.98 ± 0.69 µg/mL (control) and 3.02 µg/mL (intervention) at Day 19. Total exposure assessed by AUC7-13 and AUC13-19 did not differ significantly between the groups (p > 0.05). Incremental exposure analyses identified the post-wash-out period as the primary biologically responsive window, with higher mean incremental L+Z bioavailability in the intervention group (4.36 µg/day/mL) compared with the control group (3.00 µg/day/mL), although this difference was not statistically significant (p > 0.05). No significant effect of omega-3 co-supplementation on oxidative stress biomarkers was observed (p > 0.05). Conclusion: Omega-3 co-supplementation did not demonstrate a consistent additional benefit on L+Z bioavailability or oxidative stress markers. Day-resolved analyses using iAUC revealed temporal patterns not captured by conventional AUC measures. These exploratory findings should be interpreted with caution and confirmed in larger, longer-term studies.},
}

Humans
*Lutein/pharmacokinetics/blood/administration & dosage
*Zeaxanthins/pharmacokinetics/blood/administration & dosage
Pilot Projects
Male
*Dietary Supplements
Female
*Fatty Acids, Omega-3/administration & dosage/pharmacology
Biological Availability
*Oxidative Stress/drug effects
Adult

@article {pmid42356572,
year = {2026},
author = {García-Quintanilla, L and Almuiña-Varela, P and Rodríguez-Cid, MJ and Gil-Martinez, M and Abraldes, MJ and Gomez-Ulla, F and González-Barcia, M and Castro-Fernández, DC and Cañizo-Outeiriño, A and Cuartero-Martínez, A and Estany-Gestal, A and Otero-Espinar, FJ and Fernández-Rodríguez, M and Fernández-Ferreiro, A},
title = {Systemic Immune and miRNA Signatures Associated with Long-Term Ranibizumab Response in Neovascular Age-Related Macular Degeneration.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {19},
number = {6},
pages = {},
doi = {10.3390/ph19060955},
pmid = {42356572},
issn = {1424-8247},
support = {PI17/00940//Instituto de Salud Carlos III/ ; PI23/00069//Instituto de Salud Carlos III/ ; IN607D 2021/001//Xunta de Galicia/ ; IN607A2023/04//Xunta de Galicia/ ; },
abstract = {Objectives: To characterize the one-year functional, anatomical, and molecular responses to intravitreal Ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), and to identify systemic immune and miRNA signatures associated with treatment response. Methods: This prospective longitudinal observational study included 44 treatment-naïve patients with nAMD. Patients received up to four monthly intravitreal Ranibizumab injections, followed by a treat-and-extend regimen. Best-corrected visual acuity using ETDRS letters, central retinal thickness by optical coherence tomography, fluorescein angiography, and OCT angiography were assessed at baseline and 12 months. Peripheral blood samples were collected at both time points to quantify seven circulating cytokines using an IMMULITE chemiluminescent immunoassay and to profile 37 candidate miRNAs by TaqMan OpenArray RT-qPCR from leukocyte-derived RNA. Treatment response was classified using composite anatomical and functional criteria, including intraretinal/subretinal fluid resolution, ≥25% central retinal thickness reduction, and a ≥5 ETDRS letter gain. Results: At one year, patients showed significant central retinal thickness reduction and overall visual stabilization, although good and poor responders differed according to composite response criteria. Statin use was numerically more frequent among poor responders, although this difference was not statistically significant. Soluble IL-2R increased significantly over time in the overall cohort, mainly driven by good responders who showed higher median levels at both visits. IL-8 also increased globally, without significant between-group differences. Among differentially expressed miRNAs, miR-3121 was the only candidate reaching statistical significance and was downregulated in good responders. ROC analysis showed moderate discriminative performance for miR-3121, with an AUC of 0.76. Conclusions: One-year response to Ranibizumab in nAMD may involve systemic immune activation and miRNA regulation. miR-3121 emerges as a candidate biomarker of treatment response, supporting further validation in larger independent cohorts.},
}

@article {pmid42357377,
year = {2026},
author = {Liu, J and Wang, Z and Yang, Y and Yi, L and Li, S and Gao, J and Zhou, J and Cheng, N and Yin, X and Dong, X and Ni, J and Qu, C},
title = {Metformin and cRGDfc-Modified Nanoparticles Loaded with Curcumin for Age-Related Macular Degeneration: In Vitro Pharmacodynamics and Molecular Mechanisms.},
journal = {Pharmaceutics},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/pharmaceutics18060761},
pmid = {42357377},
issn = {1999-4923},
abstract = {Objectives: This study aimed to develop curcumin nanoparticles (Cur@PCL-PEG-MF/cRGDfc) with retinal-targeting capability and to evaluate their biological effects and pharmacological mechanisms in vitro. Methods: After synthesis of the carrier framework, metformin (MF) and cRGDfc were conjugated to the carrier material using the carbodiimide method and Michael addition reaction, respectively. Subsequently, self-assembled nanoparticles were formed from the carrier and curcumin under specific conditions. The materials were characterized by spectroscopy, chromatography, elemental analysis, energy-dispersive spectroscopy and X-ray diffraction. The efficacy of the formulation was evaluated in two cell lines, ARPE-19 and HUVEC-T1. In addition, the pharmacological mechanism was explored using transcriptome sequencing as a complementary approach. Key Findings: Self-assembled nanoparticles were successfully prepared by combining the two modified carrier materials, PCL-PEG-MF and PCL-PEG-cRGDfc, with curcumin. The nanoparticles exhibited an encapsulation efficiency of 78.09%, a particle size of 162.33 nm, and a zeta potential of -23.28 mV and displayed a spherical morphology. They showed sustained release in simulated physiological conditions and stronger affinity for ARPE-19 cells under oxidative stress. Nearly 100% of the nanoparticles were internalized by the cells, which was accompanied by reduced ROS and LDH release and decreased DNA fragmentation. In addition, the nanoparticles inhibited neovascularization by reducing VEGF-A release, thereby potentially protecting the retina in macular degeneration and reducing choroidal hemorrhage. Further analyses showed that curcumin and its nanoformulations significantly reduced the expression of inflammatory factors such as IL-1β and IL-18, lowered the protein levels of Caspase-1, GSDMD-N, and NLRP3, and increased AMPK levels. Conclusions: Using PCL-PEG as the carrier framework, MF and cRGDfc were conjugated to construct a curcumin-loaded nanoparticle with retinal-targeting capability. This nanoparticle, characterized by a small particle size, sustained release, and targeted delivery to retinal pigment epithelium (RPE) cells under oxidative stress, alleviated oxidative stress-induced damage. Its therapeutic effect may be mediated, at least in part, by interference with the AMPK/mTOR pathway and activation of the NLRP3/Caspase-1/GSDMD pathway.},
}

@article {pmid42358460,
year = {2026},
author = {Morozov, P and Andreev, V and Yakovleva, M and Kostyukov, A and Feldman, T and Ryabova, A and Romanishkin, I and Shirmanova, M and Goltsman, G and Kuzmin, V and Ostrovsky, M and Arkhipchenko, A and Maksimov, E and Becker, W and Shcheslavskiy, V},
title = {Spectral dependence of lipofuscin fluorescence lifetimes revealed by FLIM with a superconducting nanowire single-photon detector.},
journal = {Journal of biomedical optics},
volume = {31},
number = {6},
pages = {066501},
pmid = {42358460},
issn = {1560-2281},
mesh = {*Lipofuscin/chemistry/analysis ; Humans ; Retinal Pigment Epithelium/diagnostic imaging ; Microscopy, Fluorescence/methods/instrumentation ; *Nanowires/chemistry ; Macular Degeneration/diagnostic imaging ; *Optical Imaging/methods/instrumentation ; },
abstract = {SIGNIFICANCE: The noninvasive assessment of oxidative stress in the retinal pigment epithelium (RPE), a key factor in the pathogenesis of age-related macular degeneration (AMD), is an important aspect in ophthalmic diagnostics. Although fundus autofluorescence (FAF) is clinically used, its diagnostic power is limited. Fluorescence lifetime imaging ophthalmoscopy shows promise, but the photophysical underpinnings of lifetime changes in lipofuscin-the dominant RPE fluorophore-remain poorly understood. Lipofuscin granules (LGs) in the RPE are a primary source of fundus autofluorescence and are critically involved in the pathogenesis of AMD. This study characterizes the spectral and lifetime properties of LGs using a fluorescence lifetime imaging microscopy (FLIM) system integrated with a wide-range sensitivity, large-active-area superconducting nanowire single-photon detector (SNSPD) coupled with a standard 50 μ m multimode fiber.

AIM: We present experiments on multispectral fluorescence lifetime imaging with a detailed analysis of the fluorescence decays and spectral profiles of LGs in the RPE cells to probe the molecular oxidative state of RPE lipofuscin, aiming to improve AMD understanding and propose a method for early diagnosis of retinal pathologies.

APPROACH: We use a cutting-edge FLIM system integrated via a multimode fiber with a large-active-area SNSPD. Unlike previous studies, our approach provides component-resolved and spatially resolved fluorescence decay kinetics across a broad spectral range (500 to 1000 nm), which is typically inaccessible to conventional detectors. LGs were isolated from 100 human (aged 50 to 75 years) donor RPE cells and subjected to in vitro photo-oxidation to simulate AMD-like conditions. Steady-state spectroscopy revealed a blue shift in emission following photo-oxidation.

RESULTS: FLIM analysis, employing a tri-exponential decay model, showed a significant increase in the mean fluorescence lifetime τ m from ∼ 247 to ∼ 587    ps after photo-oxidation. Crucially, we identified a pronounced direct spectral dependence of fluorescence lifetimes τ m versus wavelength: for native LGs, τ m increased from 136 to 319 ps at registration range 500 to 650 nm; for photo-oxidized LGs, it increased from 174 to 623 ps over the same region. High-performance liquid chromatography confirmed the degradation of the bisretinoid A2E and accumulation of oxidized derivatives, correlating with the observed photophysical changes.

CONCLUSIONS: These findings demonstrate that component-resolved visible-near infrared spectral FLIM provides a sensitive, noninvasive approach to probe the molecular oxidative state of RPE lipofuscin, offering potential for early diagnosis of retinal pathologies.},
}

*Lipofuscin/chemistry/analysis
Humans
Retinal Pigment Epithelium/diagnostic imaging
Microscopy, Fluorescence/methods/instrumentation
*Nanowires/chemistry
Macular Degeneration/diagnostic imaging
*Optical Imaging/methods/instrumentation

@article {pmid42359432,
year = {2026},
author = {Liu, D and Bi, H and Sun, Y and Gao, Z and Lu, P},
title = {Patient Experiences of Intravitreal Anti-Vascular Endothelial Growth Factor Injections for Age-Related Macular Degeneration: A Meta-Synthesis of Qualitative Studies.},
journal = {Patient preference and adherence},
volume = {20},
number = {},
pages = {610930},
pmid = {42359432},
issn = {1177-889X},
abstract = {AIM: To synthesize evidence from qualitative studies on patients receiving intravitreal anti-vascular endothelial growth factor injections for age-related macular degeneration to explore their treatment burdens and life experiences.

METHODS: Five databases (PubMed, Web of Science, Embase, Cochrane Library, and CINAHL) were searched on 20 May 2025, with supplementation through hand-searching. The search was restricted to qualitative or mixed-methods studies published in English. The included studies were evaluated and synthesized by two independent reviewers using the Joanna Briggs Institute (JBI) critical appraisal tools and the JBI aggregative integration method.

RESULTS: Thirteen studies (2010-2023) from 11 countries were summarized into four themes: barriers to treatment and sources of anxiety, coping strategies and adaptation mechanisms, drivers of treatment adherence, and the impact of doctor-patient engagement.

CONCLUSION: Patients with age-related macular degeneration face significant physical, emotional, and logistical challenges during anti-vascular endothelial growth factor therapy. A series of measures can be integrated into the treatment process to improve patient adherence, including psychological support, structured patient education, and optimized treatment pathways.

REGISTRATION: PROSPERO CRD420251059151.},
}

@article {pmid42359981,
year = {2026},
author = {Chen, J and Yuan, XL and Zhang, X and Huang, Q and Zhou, X and Ji, D and Zhu, W and Duan, X},
title = {Genome Wide Pleiotropic Analysis Reveals Shared Genetic Architecture and Pathological Basis Between Retinitis Pigmentosa and Relevant Ocular Comorbidities.},
journal = {Seminars in ophthalmology},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/08820538.2026.2694713},
pmid = {42359981},
issn = {1744-5205},
abstract = {PURPOSE: Retinitis pigmentosa (RP) is a leading cause of irreversible blindness in working-age populations and frequently cooccurs with multiple ocular disorders. As their shared genetic basis remains poorly understood, this study aimed to elucidate the shared genetic architecture underlying RP and relevant ocular comorbidities.

METHODS: Using large-scale genome-wide association data, we systematically investigated pleiotropy, genetic correlation, cell-type specificity, and genetically predicted causality between RP and major ophthalmic comorbidities.

RESULTS: We observed significant genetic correlations and pleiotropic enrichment between RP and retinal detachments and breaks (RDAB), retinal vascular occlusion (RVO), and age-related macular degeneration (AMD), with notable SNP-level overlap between RP and primary open-angle glaucoma (POAG). RP and RDAB, as well as AMD, shared genetic associations at chr1:196176201-197311241 and chr10:123900764-125869042. Totally, 41, 25, 114, and 397 pleiotropic loci were identified between RP and RDAB, RVO, POAG, and AMD, implicating pathways related to cell division, metabolic regulation, immune activation, and complement activation. A novel causal variant (rs36212731) and four pleiotropic genes (ARMS2, HTRA1, CFH, PLEKHA1) were discovered between RP and RDAB. Ten causal variants and 24 pleiotropic genes were identified between RP and AMD. MR analyses demonstrated a genetically causal effect of RP on an increased risk of RDAB and RVO (P˂0.05), and AMD was associated with an increased risk of RP. Cell-type enrichment analyses highlighted vascular smooth muscle cells and retinal pigment epithelium as key mediators of shared susceptibility between RP and RDAB, and POAG.

CONCLUSIONS: This study reveals robust genetic and potential causal links between RP and RDAB, RVO, as well as AMD, along with complex pleiotropic associations with glaucoma. These findings provide novel genetic insights into the shared pathogenic mechanisms and generate hypotheses for future biological, translational, and clinical research.},
}

@article {pmid42360009,
year = {2026},
author = {Dogru, E and Chavez, MP and Toth, O and Serafini, M and Kabaalioglu Guner, M},
title = {Port Delivery System Vs Monthly Ranibizumab in VEGF-Driven Macular Disease: A Systematic Review and Meta-Analysis.},
journal = {Seminars in ophthalmology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/08820538.2026.2693751},
pmid = {42360009},
issn = {1744-5205},
abstract = {PURPOSE: The comparative efficacy and safety of ranibizumab Port Delivery System (PDS) vs monthly intravitreal ranibizumab in Vascular Endothelial Growth Factor (VEGF)-driven macular diseases remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing PDS vs monthly ranibizumab in neovascular age-related macular degeneration (nAMD) or diabetic macular edema (DME).

METHODS: PubMed, Embase, and Cochrane were searched for randomized controlled trials enrolling adults with neovascular age-related macular degeneration or diabetic macular edema treated with the ranibizumab Port Delivery System (100 mg/mL) versus monthly intravitreal ranibizumab 0.5 mg. This systematic review and meta-analysis was conducted according to a predefined PICOTT framework. Continuous and binary outcomes were pooled with mean differences (MDs) and risk ratios (RRs) with a 95% confidence interval (CI), respectively, with a random-effects model. Statistical analyses were performed using RevMan.

RESULTS: Three trials were included, with a total of 1,149 eyes of which 688 (60%) received PDS and 461 (40%) received monthly ranibizumab. No significant differences were observed in BCVA (nAMD: MD - 0.69 letters; 95% CI - 2.52 to 1.14; p = .46; DME: MD 0.20; 95% CI - 1.20 to 1.60; p = .78) or CRT (nAMD: MD 26.67 µm; 95% CI - 16.55 to 69.88; p = .23; DME: MD - 3.80; 95% CI - 17.20 to 9.60; p = .58). Incidence of ocular AEs was significantly higher with PDS (RR 1.80; 95% CI 1.49-2.17; p < .00001; I[2]=74%). Among specific complications, conjunctival bleb or filtering bleb leak (RR 15.29; 95% CI 2.31-101.35; p = .005), conjunctival erosion (RR 8.87; 95% CI 1.66-47.35; p = .01), vitreous hemorrhage (RR 3.61; 95% CI 1.24-10.49; p = .02), hyphema (RR 5.77; 95% CI 1.03-32.20; p = .05), and conjunctival retraction (RR 5.78; 95% CI 1.04-32.29; p = .05) occurred significantly more often with PDS. Systemic AEs were comparable between treatment arms (RR 1.00; 95% CI 0.89-1.13; p = .98).

CONCLUSION: In this systematic review and meta-analysis of three randomized controlled trials, PDS was associated with visual and anatomical results comparable to monthly ranibizumab in patients with nAMD. Evidence in DME was limited to a single trial, and conclusions in this population should be considered exploratory. PDS was associated with a higher incidence of procedure- and device-related ocular complications.},
}

@article {pmid42360388,
year = {2026},
author = {Hannig, L and Braunger, BM and Kleefeldt, N and Cagol, L and Zimmermann, J and Brunne, B and Ahmad, H and Vallon, M and Ergün, S and Hillenkamp, J and Neueder, A and Schlecht, A},
title = {Deletion of CEACAM1 does not affect retinal and choroidal morphology or transcriptome.},
journal = {Cell and tissue research},
volume = {405},
number = {1},
pages = {},
pmid = {42360388},
issn = {1432-0878},
support = {01/23//Helmut Ecker Stiftung/ ; },
mesh = {Animals ; *Choroid/metabolism/anatomy & histology ; *Retina/metabolism/anatomy & histology ; *CEACAM1 Protein/metabolism/genetics/deficiency ; *Transcriptome/genetics ; *Gene Deletion ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Carcinoembryonic Antigen ; },
abstract = {CEACAM1 (CC1) is an important mediator of cell proliferation and adhesion and serves as an angiogenic factor through interaction with VEGF. Although the role of CC1 has been extensively studied in organs such as the heart, liver and lung in which CC1 is considered an important regulator of various pathological conditions, little is known about the function of CEACAM1 in the eye. In this study, we investigated the expression and function of CC1 in the retina and choroid of healthy adult mice using immunohistochemistry, fluorescence activated cell sorting (FACS) and RNA sequencing. We found CC1 to be expressed in endothelial and myeloid cells of the retina and the choroid. However, deletion of CC1 did not result in vascular abnormalities of the retina and choroid or changes in retinal myeloid cell morphology and number. Furthermore, the retinal architecture was not affected and morphometric measurements of the thickness of the inner and outer retinal layers were not altered by deletion of CC1. Accordingly, we did not observe structural or transcriptomic changes in the choroid. Our data suggest that the role of CC1 in the adult eye during steady state is attenuated or can be compensated by other molecular mediators. However, one could speculate that CC1 may become functionally relevant during pathological conditions, such as in neovascular eye diseases like proliferative diabetic retinopathy or neovascular age-related macular degeneration.},
}

Animals
*Choroid/metabolism/anatomy & histology
*Retina/metabolism/anatomy & histology
*CEACAM1 Protein/metabolism/genetics/deficiency
*Transcriptome/genetics
*Gene Deletion
Mice
Mice, Inbred C57BL
Mice, Knockout
Carcinoembryonic Antigen

@article {pmid41068524,
year = {2026},
author = {Chourasiya, S and Patel, P and Kumar, GS and Soni, A},
title = {A New Vision for Ocular Disease: Stem Cell Strategies in Regenerative Ophthalmology.},
journal = {Stem cell reviews and reports},
volume = {22},
number = {1},
pages = {144-169},
pmid = {41068524},
issn = {2629-3277},
abstract = {Degenerative ocular diseases such as age-related macular degeneration (AMD), glaucoma, cataracts, retinitis pigmentosa (RP), dry eye disease (DED), and limbal stem cell deficiency (LSCD) are major contributors to global visual impairment and blindness. These conditions not only affect vision but also significantly reduce patients’ quality of life. Conventional therapies largely aim to manage symptoms or slow disease progression, with limited ability to regenerate or restore damaged ocular tissues. In contrast, stem cell-based therapies have emerged as a promising strategy, offering the potential to repair, replace, or regenerate dysfunctional cells within the eye. Stem cells exhibit remarkable regenerative, anti-inflammatory, and neuroprotective properties, mediated both by direct differentiation and through paracrine mechanisms such as the secretion of growth factors and exosomes. A wide range of stem cell types—mesenchymal stem cells (MSCs), retinal progenitor cells (RPCs), induced pluripotent stem cells (iPSCs), and embryonic stem cells (ESCs)—are currently under investigation for the treatment of diverse ophthalmic conditions. These therapies target various ocular structures, from the cornea to the retina, aiming to restore tissue integrity and function. This review highlights the current progress, mechanisms, and therapeutic potential of stem cell applications in ocular regeneration, and underscores their growing relevance as a regenerative solution for previously untreatable or refractory eye diseases and the clinical trials that are currently ongoing.},
}

@article {pmid41903038,
year = {2026},
author = {Palakkan, AA and Kumar, GS and Jayaraman, S and Ross, JA},
title = {Differential Effects of Retinal Fatty Acids Under Oxidative Stress Reveal DHA's Susceptibility to Ferroptosis and Polarity Disruption in iPSC Derived RPE Cells.},
journal = {Stem cell reviews and reports},
volume = {22},
number = {4},
pages = {1958-1973},
pmid = {41903038},
issn = {2629-3277},
support = {Ramalingaswami Re-entry Fellowship//Department of Biotechnology, Ministry of Science and Technology, India/ ; CRG/2022/004337//Anusandhan National Research Foundation (ANRF)/ ; },
abstract = {Age-related macular degeneration (AMD) is driven by chronic oxidative stress and lipid dysregulation in the retinal pigment epithelium (RPE), yet the specific contributions of individual retinal fatty acids remain unclear. Among these, docosahexaenoic acid (DHA)—the most abundant polyunsaturated fatty acid in the retina—may play a dual role, supporting visual function under physiological conditions but predisposing RPE cells to injury under oxidative stress. Here, we investigated how DHA and other retinal fatty acids modulate oxidative stress responses in induced pluripotent stem cell–derived RPE (iRPE) cells. Cells were exposed to DHA, arachidonic acid (ARA), or α-linolenic acid (ALA) with or without hydrogen peroxide (H2O2) to assess their effects on viability, lipid peroxidation, ferroptosis, necroptosis, barrier integrity, and VEGF secretion. Combined DHA and H2O2 exposure markedly reduced iRPE viability and trans-epithelial resistance, whereas ARA caused moderate and ALA minimal cytotoxicity. DHA uniquely induced hallmark features of ferroptosis, including lipid peroxidation, GPX4 downregulation, glutathione depletion, and iron accumulation. Treatment with ferroptosis inhibitors (ferrostatin-1, liproxstatin-1) restored viability, preserved polarity, and normalized VEGF secretion, while necroptosis inhibitors offered only partial protection. Notably, DHA-induced polarity loss occurred without activation of EMT transcription factors, revealing a ferroptosis-driven mechanism of barrier disruption. These findings identify DHA as a distinct sensitizer of ferroptosis in iRPE cells under oxidative stress, linking retinal lipid metabolism to ferroptotic vulnerability and suggesting that targeting ferroptosis may help preserve RPE integrity and slow AMD progression.Clinical Trial Number: Not applicable.},
}

@article {pmid42053728,
year = {2026},
author = {Pirillo, A and Catapano, AL},
title = {CETP Renaissance with Obicetrapib.},
journal = {Current atherosclerosis reports},
volume = {28},
number = {1},
pages = {},
pmid = {42053728},
issn = {1534-6242},
abstract = {PURPOSE OF REVIEW: This review examines the emerging role of cholesteryl ester transfer protein (CETP) inhibition, with a focus on obicetrapib, in lipid management and its potential implications beyond atherosclerotic cardiovascular disease (ASCVD), including neurodegeneration, glycaemic control, age-related macular degeneration (AMD), sepsis, and kidney function. RECENT FINDINGS: Obicetrapib is a potent, selective CETP inhibitor that overcomes the limitations of earlier agents, demonstrating substantial reductions in LDL-C, apolipoprotein B, non-HDL-C, and lipoprotein(a), alongside marked increases in HDL-C. Phase 2 and 3 trials confirm robust lipid-modifying efficacy and favourable safety. Emerging data suggest broader biological effects. Genetic and mechanistic studies link reduced CETP activity to improved brain structure and lower dementia risk, with biomarker analyses showing attenuation of Alzheimer’s disease-related markers, particularly in APOE ε4 carriers. Evidence further indicates potential metabolic benefits, including reduced risk of type 2 diabetes and improved glycaemic control. While genetic studies raise concerns about increased AMD risk, clinical trial data have not confirmed this association. Preclinical and human data suggest a protective role in sepsis via HDL-mediated endotoxin clearance, and early analyses indicate possible renal benefits through slower decline in kidney function. Obicetrapib represents a promising advancement in CETP inhibition, combining potent lipid-lowering effects with a good safety profile. Beyond cardiovascular risk reduction, emerging evidence supports potential roles in neurodegenerative disease, metabolic regulation, infection outcomes, and renal function. Ongoing outcome trials will determine its clinical impact and broader therapeutic relevance.},
}

@article {pmid42340610,
year = {2026},
author = {Volpe, G and Bonanata, M and Peyla, A and Ruscitti, L and Eggarter, V and Pache, M and Paris, A and Menghini, M and Grimaldi, G},
title = {Peripapillary Retinal Nerve Fibre and Ganglion Cell Layer Changes Following Intravitreal Aflibercept 8 mg Therapy in Neovascular Age-Related Macular Degeneration: A Longitudinal OCT Study.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42340610},
issn = {2193-8245},
abstract = {INTRODUCTION: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard of care for neovascular age-related macular degeneration (nAMD) and other retinal vascular diseases. However, transient post-injection intraocular pressure elevations have raised concerns regarding potential cumulative effects on inner retinal structures, including the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIP). As longitudinal evidence on the neuro-retinal structural safety of higher-dose formulations such as aflibercept 8 mg remains limited, this study evaluated 12-month changes in pRNFL and mGCIP thickness following intravitreal aflibercept 8 mg.

METHODS: This single-centre, observational longitudinal cohort study included patients with nAMD treated with intravitreal aflibercept 8 mg or aflibercept 2 mg. Patients receiving aflibercept 8 mg were prospectively enrolled, while patients treated with 2 mg aflibercept were retrospectively identified. Spectral-domain optical coherence tomography was used to assess pRNFL and mGCIP thickness at baseline and at 3, 6 and 12 months. Longitudinal within-eye changes relative to baseline were analysed, alongside inter-eye comparisons with fellow untreated eyes and between-treatment group comparisons at 12 months.

RESULTS: Thirty-eight eyes from 35 patients were included. In eyes treated with aflibercept 8 mg, mGCIP thickness remained stable throughout follow-up, with no significant changes at 3, 6 or 12 months compared with baseline. At 12 months, mGCIP thickness was comparable between aflibercept 8 mg-treated eyes and fellow untreated eyes, as well as between aflibercept 8 mg and aflibercept 2 mg-treated eyes. Similarly, pRNFL thickness showed no significant global or sectoral changes over 12 months and did not differ between treatment groups.

CONCLUSION: Over 12 months of follow-up, intravitreal aflibercept 8 mg was not associated with significant thinning of pRNFL or mGCIP thickness, supporting its neuro-retinal structural safety in routine clinical practice.},
}

@article {pmid42340770,
year = {2026},
author = {Malvasi, M and Fragiotta, S and Pacella, E and Scuderi, G and Abdolrahimzadeh, S},
title = {Multimodal ophthalmic imaging in the search for the association between subretinal drusenoid deposits and systemic vascular comorbidity with metabolic dysregulation in age-related macular degeneration progression.},
journal = {La Clinica terapeutica},
volume = {177},
number = {4},
pages = {720-728},
doi = {10.7417/CT.2026.2063},
pmid = {42340770},
issn = {1972-6007},
mesh = {Humans ; Disease Progression ; Female ; Male ; Aged ; Retrospective Studies ; *Retinal Drusen/diagnostic imaging/etiology/complications ; *Macular Degeneration/complications/diagnostic imaging/metabolism ; *Multimodal Imaging ; Tomography, Optical Coherence ; Aged, 80 and over ; Longitudinal Studies ; Dyslipidemias/complications ; Eye Diseases, Hereditary ; Bruch Membrane/pathology ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is increasingly linked to systemic cardiovascular and metabolic dysfunction as well as cerebral small vessel disease. Subretinal drusenoid deposits (SDD) and basal laminar deposits (BLamD) have emerged as structural biomarkers associated with AMD progression and systemic vascular compromise. This study aimed to investigate associations between hypertension, dyslipidemia, and cerebrovascular disease - transient ischemic attack, stroke, and myocardial infarction - and retinal structural alterations in AMD patients presenting SDD in order to assess the relationship with progression of disease.

METHODS: Thirty-eight eyes of 31 patients with AMD and SDD were examined in this retrospective longitudinal study. Retinal imaging, including near-infrared reflectance and spectral-domain optical coherence tomography (SDOCT), was used to characterize retinal alterations. Systemic cardiovascular and small vessel disease profiles were obtained from the clinical history. Morphometric changes in retinal layers were quantified through SDOCT and correlated with systemic metabolic and vascular parameters.

RESULTS: During a mean follow-up of 2.1 ± 0.86 years, 44.7% of eyes progressed to advanced AMD: 23.6% to complete RPE and outer retinal atrophy (cRORA)/geographic atrophy, and 21% to macular neovascularization. High-risk vascular diseases were present in 32.3% of patients. BLamD significantly increased progression risk (P = 0.03), whereas conventional drusen did not (P = 0.79). Higher serum triglycerides correlated negatively with outer retinal layer changes (r = -0.66, P = 0.004) and perifoveal thinning (r = -0.75, P < 0.001), while HDL showed positive correlations. Hypertension was frequent (87.1%) but not independently predictive of progression.

CONCLUSION: AMD patients with SDD exhibit significant associations between systemic cardio/cerebro-vascular disease and metabolic dysregulation and retinal structural degeneration. BLamD further increase progression risk, underscoring their relevance as imaging biomarkers of vascular and metabolic compromise.},
}

Humans
Disease Progression
Female
Male
Aged
Retrospective Studies
*Retinal Drusen/diagnostic imaging/etiology/complications
*Macular Degeneration/complications/diagnostic imaging/metabolism
*Multimodal Imaging
Tomography, Optical Coherence
Aged, 80 and over
Longitudinal Studies
Dyslipidemias/complications
Eye Diseases, Hereditary
Bruch Membrane/pathology

@article {pmid42341259,
year = {2026},
author = {Moir, JT and Kim, SB and Allan, KC and Kaelber, DC and Singh, RP and Talcott, KE},
title = {Demographic and Prevalence Dynamics of Macular Telangiectasia Type 2 From 2015 to 2024.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-6},
doi = {10.3928/23258160-20260513-01},
pmid = {42341259},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: This study sought to provide a recent estimate for the prevalence of macular telangiectasia type 2 (MacTel) with respect to age, race/ethnicity, and sex.

PATIENTS AND METHODS: A cross-sectional study from 2015 to 2024 was performed for adults in the United States aged ≥ 35 years within an electronic health record data platform. Patients with MacTel were identified as those with a corresponding International Classification of Diseases 10th revision (ICD-10) diagnosis code. The prevalence of MacTel was calculated at each year of the study period and stratification was performed by age, race, ethnicity, and sex.

RESULTS: In 2024, the prevalence of MacTel was 9.06 patients per 100,000, representing a 1.91-fold increase from 2015 (95% CI 1.79-2.03). Over that same timespan, the ratio of increase in MacTel was greater than the ratio of increase of age-related macular degeneration (AMD) (odds ratio 1.25, 95% 1.17-1.33).

CONCLUSION: The prevalence of MacTel is lower than previously estimated but has been increasing at a striking rate from 2015 to 2024 that outpaces AMD.},
}

@article {pmid42342678,
year = {2026},
author = {Bangar, P and Garkal, A and Mehta, T},
title = {Next-Generation Drug Delivery for Age-related Macular Degeneration: Promise of Controlled Release Formulations.},
journal = {Drug development and industrial pharmacy},
volume = {},
number = {},
pages = {1-19},
doi = {10.1080/03639045.2026.2691481},
pmid = {42342678},
issn = {1520-5762},
abstract = {OBJECTIVE: To review emerging long-acting drug delivery and implantable systems developed to overcome the limitations of conventional intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD).

SIGNIFICANCE OF REVIEW: nAMD is a leading cause of irreversible vision loss worldwide. Although intravitreal anti-VEGF injections are clinically effective, their short intraocular half-life necessitates frequent administration, resulting in high treatment burden, poor patient compliance, and increased risk of procedure-related complications. Long-acting injectable and implantable drug delivery systems offer a promising approach to maintain therapeutic drug levels while reducing injection frequency and healthcare burden.

KEY FINDINGS: Recent advances in controlled-release technologies, including electrospun nanofibers, injectable microcapsules, core-shell nanofibers, 3D-printed implants, dip-cast tubular devices, nanostructured thin-film systems, suprachoroidal implants, encapsulated cell technologies, and gene therapy-based approaches, demonstrate sustained drug release ranging from several weeks to over 1 year. These platforms provide improved drug stability, higher payload capacity, tunable release kinetics, and favorable biocompatibility. Clinically validated refillable implants, such as Susvimo™, confirm the feasibility of long-term intraocular anti-VEGF delivery.

CONCLUSIONS: Next-generation long-acting ocular drug delivery systems have the potential to transform nAMD management by reducing invasive procedures, improving patient adherence, and maintaining durable therapeutic efficacy. Continued optimization and clinical translation of these technologies are essential for their successful integration into routine ophthalmic care.},
}

@article {pmid42343082,
year = {2026},
author = {Okuda, D and Mii, S and Miyai, Y and Kato, K and Ando, R and Shiraki, Y and Esaki, N and Yamada, K and Shimizu, H and Ushida, H and Kaneko, H and Nishiguchi, KM and Enomoto, A},
title = {Possible involvement of the mesenchymal cell marker Meflin in regeneration after retinal injury.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-58893-1},
pmid = {42343082},
issn = {2045-2322},
support = {JPMJSP2125//Japan Science and Technology Agency/ ; 22K07000//Japan Society for the Promotion of Science/ ; 22H02848//Japan Society for the Promotion of Science/ ; JP24gm1210009//Japan Agency for Medical Research and Development/ ; },
abstract = {Pathological tissue remodeling, including choroidal neovascularization (CNV) and fibrosis, is central to the development of retinal diseases such as age-related macular degeneration; however, its molecular mechanisms remain incompletely defined. We examined the intraocular expression patterns of Meflin encoded by the ISLR gene, a mesenchymal stromal cell marker with anti-fibrotic properties, in human surgical specimens and mouse retinal tissues, and evaluated its involvement in a retinal injury mouse model. Meflin expression was detected in fibroblast-like stromal cells within human proliferative vitreoretinopathy / proliferative diabetic retinopathy fibrovascular membranes and the ciliary body, lens epithelium, retinal pigment epithelium, optic nerve meningeal cells, and choroidal perivascular fibroblast-like cells of the mouse eye. Lineage-tracing using a Meflin reporter mouse line revealed accumulation of Meflin-lineage cells within laser-induced CNV lesions. Notably, adeno-associated virus-mediated Meflin overexpression increased CNV volume in the acute phase of retinal injury but suppressed subretinal fibrosis after the CNV growth phase. These findings suggest that Meflin overexpression modulates angiogenic and fibrotic remodeling after retinal injury in a phase-dependent manner, consistent with reported roles in cancer and fibrotic diseases. These results improve understanding of retinal disease pathology and identify Meflin as a potential target for future therapeutic studies on proliferative and fibrotic retinal diseases.},
}

@article {pmid42343583,
year = {2026},
author = {Demirayak, B and Bozkurt, E and Tarakçıoğlu, HN and Aydoğan Gezginaslan, T and Karapapak, M and Özal, SA and Ayrancı Osmanbaşoğlu, Ö and Özdoğan Erku, S and Erdoğan, M and Sayın, N and Öztürk, M and Ağın, A and Uzundede, T and Çakır, A and Özkaya, A},
title = {Assessment of Dietary Nutritional Profile in Turkish Patients with Age-Related Macular Degeneration.},
journal = {Turkish journal of ophthalmology},
volume = {56},
number = {3},
pages = {180-186},
doi = {10.4274/tjo.galenos.2026.26641},
pmid = {42343583},
issn = {2149-8709},
mesh = {Humans ; Female ; Male ; Turkey/epidemiology ; *Macular Degeneration/epidemiology/physiopathology ; Aged ; *Nutritional Status ; Surveys and Questionnaires ; *Diet ; Aged, 80 and over ; Middle Aged ; Follow-Up Studies ; *Nutrition Assessment ; },
abstract = {OBJECTIVES: To evaluate the dietary nutritional profile according to the suggestions of the Age-Related Eye Disease Study 2 (AREDS2) in Turkish patients with age-related macular degeneration (AMD).

MATERIALS AND METHODS: The study included patients diagnosed with non-neovascular AMD in one or both eyes and who underwent routine follow-up in retina clinics at tertiary centers in İstanbul between May 12 and May 27, 2025. An ocular nutrition questionnaire prepared according to AREDS2 suggestions was translated into Turkish. The survey was conducted among our cohort after its reproducibility and validity were confirmed. Consumption of fish-shellfish, hazelnut-walnut-peanut, eggs, leafy greens, red pepper, carrot-pumpkin, and peppers-green tea-strawberry-citrus (eicosapentaenoic acid, docosahexaenoic acid, omega 3, lutein, zeaxanthin, beta-carotene, and antioxidant-rich foods, respectively), micronutrient supplementation, smoking, physical activity, anxiety about vision loss, education level, and monthly income were recorded.

RESULTS: A total of 530 patients from 7 clinics who answered all questions were evaluated. Adequate consumption of omega-3-rich foods consumption was reported by 19.3% of participants, whereas 57.2% reported no fish intake in the last week. Adequate consumption of foods rich in lutein/zeaxanthin, beta-carotene, and antioxidants was reported by 63.6%, 41.7%, and 4.7% of patients, respectively, and regular micronutrient supplementation was reported by 35.5%. Of the patients, 23.6% reported high anxiety about vision loss, 69.8% reported elementary or lower education, and 64.9% had a 20,000 TRY or lower monthly income. Micronutrient intake was positively associated with anxiety (p=0.0001) and education (p=0.02) but not with monthly income (p=0.1).

CONCLUSION: According to this first report in Turkish patients with AMD which was evaluated nutrition profile based on AREDS2 suggestions, patients showed low adherence to AREDS recommendations for micronutrient intake and lifestyle modifications. Awareness among patients and ophthalmologists needs improvement.},
}

Humans
Female
Male
Turkey/epidemiology
*Macular Degeneration/epidemiology/physiopathology
Aged
*Nutritional Status
Surveys and Questionnaires
*Diet
Aged, 80 and over
Middle Aged
Follow-Up Studies
*Nutrition Assessment

@article {pmid42345449,
year = {2026},
author = {Salabati, M and Mabudian, L and Deshmukh, S and Afshar, E and Mahmoudzadeh, R and Brar, V},
title = {Association of interleukin-6 pathway inhibition with risk of age-related macular degeneration: A propensity-matched cohort study.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261461923},
doi = {10.1177/11206721261461923},
pmid = {42345449},
issn = {1724-6016},
abstract = {PurposeTo evaluate the association between systemic tocilizumab exposure and the development of age-related macular degeneration (AMD) in a large real-world cohort.MethodsThis was a retrospective, propensity-matched cohort study including patients aged ≥40 years in the TriNetX Research Network with or without exposure to tocilizumab between May 2008 and May 2025. Patients with documented tocilizumab use were matched 1:1 to controls based on demographic and clinical characteristics within the TriNetX platform. Individuals with prior AMD were excluded from incident analyses. Risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for incident non-exudative and exudative AMD.ResultsAfter propensity score matching, 23,456 patients were included per group. Tocilizumab use was associated with a significantly lower risk of incident non-exudative AMD (RR, 0.282; 95% CI, 0.230-0.346; p < 0.001) and incident exudative AMD (RR, 0.234; 95% CI, 0.159-0.344; p < 0.001) compared with matched controls.ConclusionsSystemic tocilizumab exposure was associated with a lower incidence of both non-exudative and exudative AMD in this real-world cohort. These findings should be considered hypothesis-generating and support further study of the relationship between IL-6 signaling and AMD.},
}

@article {pmid42336230,
year = {2026},
author = {Fazal, O and Loya, A and Muayad, J and Alsoudi, AF and Bordbar, DD and Chaaya, C and Weng, CY and Rahimy, E and Patel, NA},
title = {Dopamine-Enhancing Therapies and Risk of Neovascular AMD Conversion: A Target Trial Emulation.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.06.037},
pmid = {42336230},
issn = {1879-1891},
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of central vision loss worldwide. Emerging evidence suggests that targeting dopaminergic pathways may influence AMD progression. This study evaluates whether levodopa ± carbidopa or dopamine receptor D2 (DRD2) agonists are associated with reduced risk of conversion to neovascular AMD (nAMD).

DESIGN: Population-based clinical cohort study.

PARTICIPANTS: Adults aged ≥18 years diagnosed with non-neovascular AMD between May 2005 and May 2025, within the TriNetX U.S. Collaborative Network, a federated electronic health record database spanning 69 healthcare organizations.

METHODS: This retrospective cohort study emulated four distinct target trials comparing new users of (1) levodopa (± carbidopa) or (2) DRD2 agonists (pramipexole, ropinirole, bromocriptine, rotigotine, or cabergoline) to new users of two comparators (pantoprazole or gabapentin). Patients with prior nAMD or prescriptions of other dopamine-enhancing agents (e.g., selegiline, rasagiline, tolcapone) were excluded. Each exposure group was independently matched to comparators using 1:1 propensity score matching for selected demographics, social factors, comorbidities, and AMD stage.

MAIN OUTCOME MEASURES: The primary outcome was 3-year risk of conversion from non-neovascular AMD to nAMD. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. An α level of 0.05 was used to determine statistical significance.

RESULTS: Patients prescribed levodopa ± carbidopa had a reduced 3-year risk of conversion to nAMD relative to their matched counterparts prescribed pantoprazole (levodopa n=1312, control n=1312; HR 0.67; 95% CI, 0.45-0.98) and gabapentin (levodopa n=1675, control n=1675; HR 0.69; 95% CI, 0.50-0.95). No significant difference was observed in 3-year risk of conversion to nAMD between DRD2 agonists use relative to pantoprazole (DRD2 n=1603, control n=1603; HR 0.81; 95% CI, 0.58-1.13) or gabapentin (DRD2 n=2779, control n=2779; HR 0.92; 95% CI, 0.72-1.19).

CONCLUSIONS: In this cohort study, levodopa ± carbidopa use was associated with lower 3-year risk of conversion to nAMD in two independent matched comparisons, whereas DRD2 agonists were not associated with significant differences in risk. These findings suggest dopaminergic signaling may influence AMD progression and warrant further prospective investigation.},
}

@article {pmid42336282,
year = {2026},
author = {Enyong, EN and Bankole, OO and Gurley, JM and McClellan, ME and Liu, L and Ding, SY and Agbaga, MP and Chucair-Elliott, AJ and Ash, JD and Elliott, MH},
title = {Non-caveolar caveolin-1 in retinal Müller glia promotes innate immune responses.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113290},
doi = {10.1016/j.jbc.2026.113290},
pmid = {42336282},
issn = {1083-351X},
abstract = {Caveolae are specialized plasma membrane invaginations implicated in ocular diseases including primary open angle glaucoma, diabetic retinopathy and age-related macular degeneration. Caveolin-1 (CAV1) typically functions within caveolae where it associates with a co-regulatory protein, CAVIN1 (also known as polymerase I and transcript release factor; PTRF), which is necessary for caveolae formation. However, CAV1 can also reside outside of caveolae in planar "scaffolds," though the function of this non-caveolar CAV1 remains unclear. Here we show that Müller glia, the major macroglial cells of the retina, abundantly express CAV1 with minimal CAVIN1/PTRF expression both in situ and in the MIO-M1 Müller glial cell line. Transmission electron microscopy confirmed that morphologically identifiable caveolae are virtually absent in Müller glia, indicating that CAV1 is predominantly non-caveolar. Transgenic CAVIN1/PTRF expression induced caveolae formation, demonstrating functional competence. Non-caveolar CAV1 in MIO-M1 Müller glia promoted Toll-like receptor-4 (TLR4) signaling, as either CAV1 silencing or its sequestration into caveolae by CAVIN1/PTRF overexpression significantly suppressed lipopolysaccharide (LPS)-induced interleukin-6 (IL-6) upregulation through reduced NF-κB activation. Conversely, in human retinal endothelial cells (HRECs) where CAV1 predominantly localizes to caveolae, CAV1 silencing enhanced inflammatory responses. These results demonstrate that non-caveolar CAV1 in Müller glia promotes a pro-inflammatory phenotype that can be attenuated by CAV1 silencing or sequestration into caveolae, suggesting cell context-specific roles for CAV1 in inflammatory regulation with potential therapeutic implications for ocular inflammatory diseases.},
}

@article {pmid42336619,
year = {2026},
author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Wang, YX and Nangia, V and Panda-Jonas, S},
title = {Estimation of high myopia-associated optic neuropathies: the Two-Continent Eye Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2026-329849},
pmid = {42336619},
issn = {1468-2079},
abstract = {PURPOSE: To estimate probabilities of high myopia-associated glaucomatous/glaucoma-like optic neuropathy (GLON) and non-glaucomatous optic neuropathy (NGON).

METHODS: Participants of four population-based investigations (Beijing Eye Study (n=3316 participants; age: 40+ years), Ural Eye and Medical Study (n=5372; age: 40+ years), Ural Very Old Study (n=586; age: 85+ years), Ural Children Eye Study (n=4328; age: 6+ years), Central India Eye and Medical Study (n=4374; age: 30+ years) underwent medical and ophthalmological examinations.

RESULTS: The study population (n=35 167 eyes; 17 996 individuals) was randomly divided (ratio: 1:1) into a development and validation subgroup. In the development subgroup, the GLON prevalence equation was: -20.221+0.359×Axial Length+0.083×Age+0.706×Indian Ethnicity+0.198×Intraocular Pressure (IOP)+0.780×NGON-Presence. The NGON prevalence equation was: -38.136+1.202×Axial Length+0.038×Age-2.745×Indian Ethnicity+0.566×Myopic Macular Degeneration Stage+1.300×GLON Presence. In the validation subgroup, these equations had an area under the receiver operating characteristic curve for GLON prevalence and NGON prevalence of 0.881 and 0.964, respectively. Applying the equations, a non-Indian individual (axial length: 28 mm; IOP: 22 mm Hg) had a GLON probability of 3.5% and 60.2% at the ages of 30 years and 75 years, respectively, and an NGON probability of 3.42% and 16.4%, respectively. With an axial length of 30 mm, GLON probability and NGON probability increased from 6.9% to 75.6% and from 28.2% to 68.4% from age 30 years to 75 years.

CONCLUSIONS: The equations offer a rough estimate of optic nerve damage probability at present and at older age, based on axial length, IOP, ethnicity and ocular comorbidity. The calculated probability of GLON and NGON (IOP: 22 mm Hg, age: 75 years) at an axial length of 28 mm was 60.2% and 16.4%, respectively, and 75.6% and 68.4%, respectively, for an axial length of 30 mm.},
}

@article {pmid42336620,
year = {2026},
author = {Wu, AL and Guo, Y and Hormel, TT and Flaxel, CJ and Hwang, TS and Huang, D and Jia, Y and Bailey, ST},
title = {Drusen volume and reticular pseudodrusen volume from optical coherence tomography with deep learning as risk factors for progression to late age-related macular degeneration in eyes with reticular pseudodrusen and contralateral macular neovascularisation.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329021},
pmid = {42336620},
issn = {1468-2079},
abstract = {AIM: To implement a deep learning-based segmentation algorithm to quantify reticular pseudodrusen (RPD) and drusen volumes on optical coherence tomography (OCT) and investigate their association with progression to late age-related macular degeneration (AMD).

METHODS: A retrospective analysis included study eyes with RPD and contralateral neovascular AMD using 6×6 mm macular OCT (Solix; Visionix/Optovue, Inc). Automated segmentation quantified RPD and drusen volumes, including large drusen and drusenoid pigment epithelial detachment (PED), and late AMD development was evaluated over 2 years. Associations between baseline volumetric biomarkers and progression were evaluated using Cox proportional hazards models.

RESULTS: Fifty-one eyes (mean age 74.9±7.65 years) were included. The median (IQR) baseline RPD volume was 0.018 mm³ (0.004-0.52) and total drusen volume was 0.009 mm³ (0.001-0.064). Over 24.2±1.20 months, late AMD developed in 20 eyes (39.2%). In multivariable Cox regression models adjusted for age, each 0.01 mm³ increase in baseline RPD volume (HR: 1.082; p=0.002) and total drusen volume (HR: 1.080; p<0.001) were associated with progression to late AMD. In an exploratory drusen subtype analysis, progression to late AMD was independently associated with baseline RPD volume, large drusen volume and drusenoid PED volume.

CONCLUSION: The deep learning-based volumetric segmentation tool allows OCT-derived automated volume quantification of different types of drusen based on OCT. In eyes with RPD and contralateral neovascular AMD, greater RPD volume and large drusen and/or drusenoid PED volume carried greater risk of developing late AMD in 2 years.},
}

@article {pmid42337105,
year = {2026},
author = {Kazantzis, D and Keskin, AM and Thottarath, S and Kubravi, HS and Sheemar, A and Sivaprasad, S and , },
title = {Prevalence of bacillary layer detachment (BALAD) in treatment naive neovascular age-related macular degeneration (nAMD) and response to treatment after loading phase of aflibercept 2 mg: PRECISE study report 9.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42337105},
issn = {1476-5454},
abstract = {PURPOSE: To estimate the prevalence of BALAD in Treatment Naïve nAMD patients in the PRECISE study and report the response after loading phase of 2 mg aflibercept treatment.

METHODS: The PRECISE study included patients aged above 50 years with treatment naïve nAMD and a baseline visual acuity (VA) between 24 and 78 letters ETDRS. All participants received three monthly aflibercept 2 mg injections followed by 8-week post-treatment follow up. BALAD prevalence, baseline clinical characteristics and the visual and anatomical response to aflibercept loading were evaluated.

RESULTS: Among the 1981 eligible eyes, BALAD was observed in 69 eyes (3.6%). BALAD was found in 2.7% of eyes with type 1 MNV, 6.8% of eyes with type 2 MNV, 0.5% of eyes with retinal angiomatous proliferation (RAP) and in 1.6% of eyes with polypoidal choroidal vasculopathy (PCV) (p < 0.0001). Eyes with BALAD at baseline had significantly lower VA and higher CST compared to eyes without BALAD. BALAD resolved in 63 out of 69 eyes (91.3%). VA improved and CST reduced post-treatment. Fibrosis was observed in 28 (40.6%) and ellipsoid zone disruption in 55 (79.7%) out of 69 eyes in the final visit.

CONCLUSIONS: This study estimated that BALAD was present in 3.6% of eyes with treatment naïve nAMD and occurred more frequently in type 2 MNV. Although BALAD resolved in 91.3% of eyes and visual and anatomical recovery was achieved, eyes with BALAD showed a frequent early association with fibrosis and ellipsoid zone disruption at the post-loading phase visit.},
}

@article {pmid42337629,
year = {2026},
author = {Egger, D and Amesbauer, F and Mohamed, H and Thiel, KE and Angermann, R and Waldstein, SM},
title = {Real-world outcomes after switching to faricimab in previously treated neovascular age-related macular degeneration: longitudinal outcomes up to 24 months.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00889-0},
pmid = {42337629},
issn = {2056-9920},
abstract = {BACKGROUND: In neovascular age-related macular degeneration (nAMD), persistent disease activity despite anti-VEGF therapy is common. Switching to faricimab may improve outcomes and extend treatment intervals in treatment-resistant patients, but long-term real-world data remain limited.

METHODS: In this retrospective, single-centre study, 43 eyes of 38 patients with treatment-resistant nAMD were switched to faricimab and followed for up to 24 months. Insufficient disease control was defined as inability to extend treatment intervals beyond 8 weeks under a treat-and-extend regimen. Outcomes included best-corrected visual acuity (BCVA), central subfield thickness (CST), pigment epithelial detachment (PED) height, fluid status, and treatment intervals. Longitudinal changes were analysed using mixed-effects models. Exploratory analyses of baseline and early response predictors were performed.

RESULTS: Mean BCVA remained stable throughout follow-up, with no significant change from baseline at any time point (p > 0.05). CST decreased significantly at all visits, ranging from - 45.8 μm (95% CI - 65.3 μm to - 26.3 μm) at 1 month to - 52.3 μm (95% CI - 73.7 μm to - 30.8 μm) at 24 months (p < 0.001). PED height decreased at 1 month (- 19.0 μm; 95% CI - 33.6 μm to - 4.4 μm, p = 0.011) and remained reduced from 12 to 24 months, ranging from - 25.9 μm (95% CI - 39.7 μm to - 12.1 μm, p < 0.001) to - 49.1 μm (95% CI - 65.1 μm to - 33.0 μm, p < 0.001). Presence of subretinal fluid decreased significantly at all time points, with odds ratios (OR) ranging from 0.064 (95% CI 0.01 to 0.41, p = 0.004) at 1 month to 0.012 (95% CI 0.01 to 0.10, p < 0.001) at 24 months, whereas intraretinal fluid showed a variable response, with a significant reduction observed at 3 months only (OR 0.204, 95% CI 0.05 to 0.79, p = 0.021). The proportion of eyes with a dry macula increased from 0% at baseline to 23.1% at 12 months and 24.0% at 24 months. Treatment intervals extended from 5.9 ± 1.2 weeks before switch to 8.7 ± 2.6 weeks at 12 months (p < 0.001) and 10.6 ± 3.0 weeks at 24 months (p < 0.001). No adverse events were observed.

CONCLUSION: Switching to faricimab was associated with improved anatomical outcomes and extended treatment intervals while maintaining stable visual acuity, suggesting benefits primarily related to anatomical control and reduced treatment burden.},
}

@article {pmid42339613,
year = {2026},
author = {Panos, GD and Vagiakis, I and Empeslidis, T and Amoaku, W and Konstas, AG},
title = {Retinal anti-VEGF treatment now, and what next? From loading doses to long-game thinking.},
journal = {Expert opinion on pharmacotherapy},
volume = {},
number = {},
pages = {},
doi = {10.1080/14656566.2026.2695091},
pmid = {42339613},
issn = {1744-7666},
}

@article {pmid42339716,
year = {2026},
author = {Kelkar, A and Kelkar, J and Garg, Y and Jain, HH and Sengupta, S},
title = {Smartphone-based offline AI for multi-disease retinal screening: Real-world accuracy.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261462321},
doi = {10.1177/11206721261462321},
pmid = {42339716},
issn = {1724-6016},
abstract = {ObjectiveTo evaluate the diagnostic accuracy of a multi-disease offline artificial intelligence system (Medios-AI, MAI), integrated into a smartphone-based fundus camera, for simultaneous screening of diabetic retinopathy (DR), glaucoma, and age-related macular degeneration (AMD) in a real-world setting.MethodsIn this prospective cross-sectional study, 193 adults (371 eyes) aged ≥18 years with DR, glaucoma, AMD, or normal fundus were enrolled between May and December 2024. Dilated fundus imaging was performed using the Remidio Fundus on Phone (FoP) and Zeiss Clarus 500 cameras. Ungradable images were excluded. The offline MAI algorithm generated disease-specific reports, which were compared to masked grading of Clarus images by two fellowship-trained ophthalmologists. In ambiguous cases, the AI report defaulted to "either DR or AMD."ResultsMAI achieved sensitivity of 99.3% (95% CI: 96-100), specificity of 95.7% (95% CI: 92-98), and AUROC of 0.99 for detecting any retinal disease. For glaucoma (n = 109), sensitivity was 98.2% (95% CI: 94-100), specificity 99.0% (95% CI: 97-100), AUROC 0.99. For AMD (n = 56), sensitivity was 88.9% (95% CI: 77-96), specificity 97.5% (95% CI: 95-99), AUROC 0.93. For DR (n = 78), sensitivity was 84.6% (95% CI: 75-92), specificity 99.0% (95% CI: 97-100), AUROC 0.92. Agreement on vertical cup-to-disc ratio between AI and graders ranged from -0.1 to +0.1, with intergrader ICC of 0.97 (P < 0.001 for all comparisons).ConclusionsMAI demonstrated significant diagnostic accuracy for DR, glaucoma, and AMD using an offline, smartphone-based platform, supporting scalable, point-of-care retinal screening in resource-limited settings.},
}

@article {pmid42340411,
year = {2026},
author = {Romano, E and Capuano, V and Fragiotta, S and Parravano, M and Beretta, F and Sacconi, R and Lambiase, A and Souied, EH and Querques, G},
title = {Pachy-reticular pseudodrusen associated with pachyvitelliform maculopathy.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42340411},
issn = {1435-702X},
abstract = {PURPOSE: To characterize the phenotype of pachy-reticular pseudodrusen (pachy-RPD) associated with pachyvitelliform maculopathy (PVM).

METHODS: A retrospective, case-control study of patients over 50 with pachy-RPD (choroidal thickness > 250 μm) associated with PVM. Acquired vitelliform lesions (AVL) without other comorbidities were included as controls. Medical records and multimodal imaging from two tertiary centers were analyzed, including structural optical coherence tomography (OCT), fundus autofluorescence, OCT angiography (OCTA), and dye-based angiography.

RESULTS: Twenty-five eyes of 17 patients (mean age 74 ± 11 years) fulfilled the inclusion criteria. Best-corrected visual acuity was 20/64 (range 20/32 to 20/250). Most of the lesions were unilateral (59%) with foveal involvement. Pachy-RPD/PVM eyes had smaller lesions, lower central macular thickness (p = 0.04), lesion height (p = 0.008), and lesion width (p < 0.001) compared to AVL eyes. Despite this, pachy-RPD/PVM eyes presented more frequent external limiting membrane discontinuities (56% vs. 27%, p = 0.03) and hypertransmission (68%) compared to AVL eyes (8%, p < 0.001). Six out of 25 eyes (24%) of PVM cases showed late-stage complications in the fellow eye, including type 1 macular neovascularization (4 eyes) and macular atrophy (2 eyes). These eyes exhibited thinning of the outer retina (306 ± 32 μm vs. 277 ± 13 μm, p = 0.007) and macular cube (9.1 ± 1.0 mm³ vs. 8.1 ± 0.4 mm³, p = 0.01).

CONCLUSION: Pachy-RPD and PVM represent a phenotypic variant within the heterogenous spectrum of vitelliform lesions. The present study highlights distinct imaging and morphological features of pachy-RPD/PVM compared to AVL, revealing a stronger association between choroidal status, outer retina involvement, and hypertransmission.},
}

@article {pmid42331015,
year = {2026},
author = {Prinz, J and Prokosch, V},
title = {Malnutrition as a Risk Factor for Cerebral and Glaucomatous Neurodegeneration - Mechanisms and Therapeutic Strategies.},
journal = {Klinische Monatsblatter fur Augenheilkunde},
volume = {},
number = {},
pages = {},
doi = {10.1055/a-2841-0517},
pmid = {42331015},
issn = {1439-3999},
abstract = {ABSTRACT: BACKGROUND: Neurodegenerative diseases are an increasing challenge for healthcare systems in the context of demographic change. They affect the central nervous system, including the brain-manifesting, for example, as dementia-as well as the retina, as seen in glaucoma or age-related macular degeneration. Malnutrition-defined as quantitative or qualitative under- or overnutrition-affects key mechanisms that contribute to neuronal and retinal neurodegeneration.

ABSTRACT: OBJECTIVE: The aim of this study is to systematically present the pathophysiological mechanisms of malnutrition-related neurodegeneration, to evaluate the current evidence on dietary patterns and cognitive health, and to derive practical clinical strategies for nutritional optimization.

ABSTRACT: METHODS: Narrative literature review based on peer-reviewed publications from the fields of nutritional medicine, geriatrics, neurology, ophthalmology, and public health.

ABSTRACT: RESULTS: Malnutrition promotes oxidative stress, mitochondrial dysfunction, chronic neuroinflammation, and vascular dysregulation, and it influences neurotransmitter synthesis. These mechanisms are relevant to both cerebral and ocular neurodegenerative processes. The Mediterranean diet and the MIND diet are associated with a significantly reduced risk of cognitive impairment; for ocular diseases, interventional studies in age-related macular degeneration in particular demonstrate protective effects of antioxidant supplementation, whereas evidence for glaucoma is currently based predominantly on observational data. Screening approaches and micronutrient diagnostics enable early identification of at-risk individuals. Building on this, individualised dietary interventions and targeted supplementation of selected nutrients could be potentially preventive and stabilising therapeutic strategies.

ABSTRACT: CONCLUSION: Malnutrition is a key modifiable risk factor for neurodegenerative diseases of the brain and retina. More intense integration of nutritional diagnostics and therapy into neurological, geriatric, and ophthalmological care structures appears warranted.},
}

@article {pmid42331067,
year = {2026},
author = {Ashourizadeh, H and Gilbert, JB and Ross, C and Kearney, WC and Grinspan, N and Elze, T and Vavvas, DG and Miller, JW and Lorch, AC and Armstrong, GW and , },
title = {Cataract Surgery and the Risk of Conversion from Dry to Neovascular Age-related Macular Degeneration in the IRIS© Registry.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.06.016},
pmid = {42331067},
issn = {1549-4713},
abstract = {OBJECTIVE: To evaluate the association between cataract surgery (CS) and the risk of conversion from dry age-related macular degeneration (dAMD) to neovascular AMD (nvAMD), and to identify factors associated with conversion.

DESIGN: Population-based retrospective time-to-event study SUBJECTS: Eyes of patients aged ≥55 years with early or intermediate dAMD and phakic status at baseline were identified in the American Academy of Ophthalmology IRIS® Registry (Intelligent Research in Sight) on or after January 1st, 2016, to December 31st, 2022. Eyes that underwent CS were classified as exposed; those without CS during the study period were nonexposed.

METHODS: Propensity score matching was used to match eyes 1:1 on age, sex, race, and ethnicity, laterality, AMD stage, and smoking status. CS was modeled as a time-varying exposure. We used Cox proportional hazards regression to estimate the hazard of conversion to nvAMD.

MAIN OUTCOME MEASURES: Conversion from dAMD to nvAMD, defined by registry-derived diagnosis codes, between exposed and nonexposed cohorts.

RESULTS: After matching, 40,053 eyes were included in each exposed and nonexposed cohort (total N = 80,106 eyes). CS was associated with a higher risk of nvAMD conversion (hazard ratio [HR] = 1.22; 95% CI, 1.16-1.30; P < 0.001). Time-varying analysis demonstrated that this association was strongest early in follow-up (HR ≈ 2.5 in year 1) and declined steadily, reaching non-significance (HR ≈ 1.0) by year 4. At year 6, the cumulative incidence of nvAMD was 17.7% in the exposed cohort versus 15.2% in the nonexposed cohort. Baseline AMD stage moderated the effect of CS, with weaker effects of CS for intermediate AMD (Interaction HR = 0.82, 95% CI, 0.78-0.92).

CONCLUSIONS: CS was associated with a modestly increased overall rate of conversion from dAMD to nvAMD; however, the time-dependent pattern suggests that the observed association likely reflects increased surveillance or unrecognized pre-existing nvAMD rather than a sustained biological effect of surgery. The absolute risk difference was small (∼3.3% over six years). These findings support careful perioperative evaluation in dAMD patients but do not implicate CS as a long-term driver of neovascular conversion.},
}

@article {pmid42331911,
year = {2026},
author = {Vijay Singh, SH and Yeap, W and Too, LK and Allende, A and Hall, G and Hunyor, A and Madigan, MC and Merani, R and Ortiz, J and Rodriguez, M and Wong, J and Invernizzi, A and Killingsworth, M and Pye, V and Mehta, H and Petsoglou, C and Cherepanoff, S},
title = {A combined ex vivo fundus imaging-histology protocol for clinicopathological validation of human donor eyes with limited medical history.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-58078-w},
pmid = {42331911},
issn = {2045-2322},
abstract = {This study evaluated a combined ex vivo fundus imaging-histology protocol to improve accuracy of diagnosis in human donor eyes with limited medical history. Fifty-one formalin-fixed eyes from 32 donors underwent a standardised workflow comprising ex vivo fundus photography, selective spectral-domain optical coherence tomography (SD-OCT), and comprehensive histological examination. Medical/surgical retinal ophthalmologists independently reviewed imaging, while ophthalmic pathologists performed masked histological assessment. Diagnostic metrics were calculated using histology as the reference standard. Ex vivo imaging identified definitive pathology in 10 of 51 eyes (19.6%) and possible abnormalities in 4 eyes (7.8%). Histological analysis, however, revealed definitive pathology in 20 eyes (39.2%), detecting a broader range of diseases, including early age-related macular degeneration, hypertensive vasculopathy, and a rare choroidal tumour. Concordance was observed in 27 eyes (52.9%), mainly where no pathology was present. Significant discordance occurred in 24 eyes (47.1%), comprising 13 false negatives and 11 false positives (including misclassified pathology). Consequently, the sensitivity and specificity of ex vivo imaging for detecting pathology were 18.8% and 68.6%, respectively. While ex vivo imaging is a practical screening tool, imaging alone may miss or misclassify pathology due to postmortem artefacts and a lack of validated interpretive criteria. A combined imaging-histology approach validates the limited tissue available from eye-bank programs and maximises research value.},
}

@article {pmid42332210,
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, NA},
title = {Summary of Research: 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 = {42332210},
issn = {2193-8245},
abstract = {This is a summary of the original research article "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." Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are eye diseases that can be treated with anti-vascular endothelial growth factor (anti-VEGF) therapies. As these therapies are given by injections into the eye, reducing the number of injections could reduce the treatment burden on patients and healthcare providers. Aflibercept 8 mg and faricimab treat-and-extend (T&E) may enable longer dosing intervals compared with other available anti-VEGF therapies for patients with DME and nAMD; however, they have not been compared against each other directly in clinical trials. This study used a statistical method called a network meta-analysis (NMA) to compare aflibercept 8 mg and faricimab T&E by synthesizing data from clinical trials, enabling an indirect comparison in the absence of head-to-head studies. Outcomes included the mean number of injections, changes in vision [best-corrected visual acuity (BCVA)] and changes in macula thickness [central subfield thickness (CST)]. CST should reduce if the treatment is working. On the basis of indirect comparison of available clinical trial data, this exploratory study found that there were significantly fewer injections with aflibercept 8 mg treatment compared with faricimab T&E over 2 years, for both patients with DME and nAMD, and there were no significant differences between the two medications for BCVA or CST changes. NMAs are based on indirect comparisons and therefore have limitations, and clinical trials or real-world studies would be required to confirm these conclusions. Please refer to the original article for further details on the methods and limitations of this analysis.},
}

@article {pmid42332292,
year = {2026},
author = {Owsley, C and Curcio, CA},
title = {Impaired Rod-Mediated Vision is the Functional Hallmark of Ageing and Early and Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {},
number = {},
pages = {},
pmid = {42332292},
issn = {1475-1313},
support = {R01AG04212/AG/NIA NIH HHS/United States ; R01EY029595/EY/NEI NIH HHS/United States ; R01EY029595/EY/NEI NIH HHS/United States ; },
abstract = {Laboratory and patient-oriented research on photoreceptors and vision in ageing and early and intermediate age-related macular degeneration (AMD) were conducted in parallel starting in the 1990s by Christine Curcio and Cynthia Owsley, respectively. They joined forces in two longitudinal observation studies, the Alabama Study on Age-related Macular Degeneration (ALSTAR) in 2009 and in ALSTAR2 in 2019, together involving >1100 participants. These studies established rod-mediated dark adaptation (RMDA) measured close to the fovea as the first functional biomarker for incident early AMD and the progression of AMD. These studies used standardised grading of colour fundus photography and prioritised large samples for statistical power. RMDA is a global measure of dysregulated transport between the circulation and photoreceptors, involving at least seven different steps in a retinoid re-supply route especially needed by rods, and a surrogate for the delivery of other essentials across this route. The choice of functional and imaging outcome measures was informed by a model of AMD pathophysiology based on drusen biology, as discovered in the laboratory using high-quality human donor eyes. Specifically, high-risk drusen in the central retina were thought to result from large lipoproteins constitutively made by the retinal pigment epithelium and impaired in transit to circulation by ageing changes in Bruch's membrane and choriocapillaris. Imaging studies in ALSTAR/2 thus included optical coherence tomography (OCT) angiography assessments of choriocapillaris flow signal and OCT assessments of outer bands involved in intercellular transfer (interdigitation zone). Of seven vision tests utilised in ALSTAR2, only RMDA achieved a Minimum Clinically Important Difference at 3 years follow-up. This research highlights the importance of developing functionally valid structural endpoints for use in early and intermediate AMD intervention trials. Research to date supports the idea that functional changes emerge earlier than structural changes in early and intermediate AMD. Clinicaltrials.gov # NCT04112667 (registration date October 7, 2019).},
}

@article {pmid42333298,
year = {2026},
author = {Dasan, R and Chen, MY and Du, J and Do, BK and Osman, DH and Williams, BK and Ali, MH},
title = {Association Between the Social Deprivation Index and Neovascular Age-Related Macular Degeneration Outcomes.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261442916},
pmid = {42333298},
issn = {2474-1272},
abstract = {Purpose: To evaluate whether disease severity at diagnosis and treatment outcomes in patients with neovascular age-related macular degeneration (nAMD) may be stratified by the Social Deprivation Index (SDI; a measure of socioeconomic status [SES] where higher scores indicate greater socioeconomic deprivation). Methods: We conducted a retrospective cohort study of 643 adults with newly diagnosed unilateral nAMD who were treated with antivascular endothelial growth factor (anti-VEGF) therapy at the Retina Group of Washington. Data collected included best-corrected visual acuity (BCVA) at baseline and 12 months, presence of submacular hemorrhage, and injection frequency in the first year of treatment. Logistic regression was used to assess associations between SDI and BCVA outcomes. Results: A higher SDI score was associated with lower odds of achieving a BCVA of ≥20/40 at 12 months (odds ratio, 0.69, 95% CI, 0.48-0.98; P = .039). Submacular hemorrhage and non-White race were predictive of poorer outcomes, whereas sex at birth was not predictive. The number of anti-VEGF injections received over 12 months was similar between the high SDI quantile group and low SDI quantile group (mean 9.1 vs 8.8; P = .053). Age, baseline BCVA ≥20/40, and race were significant predictors of achieving a BCVA ≥20/40 at 12 months. BCVA at baseline was not significantly different between the SDI quantile groups, suggesting that disparities emerge during treatment rather than at diagnosis. Conclusions: The SDI is a useful metric of social determinants of health in patients with nAMD. Higher SDI was associated with poorer visual outcomes despite similar baseline vision and treatment exposure, suggesting that disparities extend beyond diagnosis to treatment effectiveness. These findings underscore the multifactorial nature of socioeconomic influences, including race, treatment adherence, and access, and the need for targeted strategies to improve equitable care.},
}

@article {pmid42333299,
year = {2026},
author = {Berkowitz, ST and Gilbert, JB and Ross, CJ and Kearney, WC and Lorch, A and Miller, JW and Rossin, EJ and Sternberg, P and Finn, AP},
title = {Intravitreal Anti-VEGF Injection Transitions Across Bevacizumab, Biosimilar, and Branded Medications: The IRIS Registry Study.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261455206},
pmid = {42333299},
issn = {2474-1272},
abstract = {Purpose: To characterize antivascular endothelial growth factor medication transitions among patients with neovascular age-related macular degeneration (nAMD), including delays in care and economic impacts. Methods: A retrospective observational cohort study analyzed participants with nAMD in the IRIS (Intelligent Research in Sight) Registry who were treated with antivascular endothelial growth factor agents from 2015 to 2024. Four cohorts were analyzed: (1) bevacizumab only, (2) bevacizumab transitioned to a biosimilar, (3) bevacizumab transitioned to a branded agent, and (4) bevacizumab transitioned to a biosimilar and then to a branded agent. The main outcome measures were number of intravitreal injection events, transitions in medications, and injection intervals. Results: A total of 182 757 eyes with nAMD met inclusion criteria: 136 451 received bevacizumab only; 2184, bevacizumab followed by a biosimilar; 335, bevacizumab followed by a biosimilar, followed by branded medication; and 43 787, bevacizumab followed by a branded agent. Newer agents (faricimab and aflibercept 8 mg) experienced additional delays of 8.6 days compared with aflibercept 2 mg (P < .001). Economic modeling based on IRIS transition rates and medication cost showed that bevacizumab transitioned to a biosimilar and then to a branded agent was 36.3% and 11.62% more costly than bevacizumab transitioned to a biosimilar (P < .001) and bevacizumab transitioned to a branded agent (P < .001), respectively, within 2 years. Similar cost differences persisted in 5- and 10-year projections. Bevacizumab transitioned to a biosimilar and then to a branded agent was the costliest pathway compared with transitions to biosimilars and branded agents, regardless of which branded agent was used. Conclusions: IRIS Registry cohort data suggest possible demographic differences in patients undergoing medication transitions, including biosimilar agents, as well as delays in care with medication transitions. Economic simulations suggest that multiple transitions may be more costly than direct transitions from bevacizumab to either biosimilar or branded agents.},
}

@article {pmid42333946,
year = {2026},
author = {Jang, HY and Choi, S and Kim, SJ and Kim, S and Jo, DH and Lee, TG and Park, KS and Kim, JH},
title = {Humanin Mitigates Aβ-Induced Retinal Pigment Epithelium Injury via AMPK-Beclin1-Dependent Mitophagy.},
journal = {Aging cell},
volume = {25},
number = {7},
pages = {e70601},
doi = {10.1111/acel.70601},
pmid = {42333946},
issn = {1474-9726},
support = {2022M3A9E4017127//National Research Foundation of Korea/ ; RS-2023-00260351//National Research Foundation of Korea/ ; 202200004004//Kun-hee Lee Child Cancer and Rare Disease Project/ ; 18-2023-0010//Seoul National University Hospital/ ; GTL25021-000//National Research Council of Science and Technology/ ; },
mesh = {*Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; *Mitophagy/drug effects ; *Amyloid beta-Peptides/metabolism/toxicity ; *Beclin-1/metabolism ; *AMP-Activated Protein Kinases/metabolism ; *Intracellular Signaling Peptides and Proteins/metabolism/pharmacology ; Mitochondria/metabolism/drug effects ; Animals ; Cell Line ; Phosphorylation/drug effects ; Macular Degeneration/metabolism/pathology ; },
abstract = {Amyloid beta (Aβ), a key component of drusen in age-related macular degeneration (AMD), induces oxidative stress, mitochondrial dysfunction, and degeneration in the retinal pigment epithelium (RPE), contributing to progressive vision loss in the elderly. We investigated the protective role of Humanin (HN), a mitochondria-derived peptide with known neuroprotective effects in Aβ-related neurodegenerative diseases, in retinal pathology induced by subretinal injection of FITC-labeled Aβ. HN enhanced the clearance of Aβ-accumulated mitochondria in the RPE while preserving retinal function and RPE barrier integrity. In ARPE-19 cells, HN activated AMP-activated protein kinase (AMPK), leading to phosphorylation of ULK1 and Beclin1, which promoted the interaction between Beclin1 and Parkin and their translocation to mitochondria. This process facilitated the removal of Aβ-accumulated mitochondria in the RPE. Our results demonstrate that targeting mitophagy in the RPE with HN may offer a promising therapeutic strategy for AMD.},
}

*Retinal Pigment Epithelium/metabolism/pathology/drug effects
Humans
*Mitophagy/drug effects
*Amyloid beta-Peptides/metabolism/toxicity
*Beclin-1/metabolism
*AMP-Activated Protein Kinases/metabolism
*Intracellular Signaling Peptides and Proteins/metabolism/pharmacology
Mitochondria/metabolism/drug effects
Animals
Cell Line
Phosphorylation/drug effects
Macular Degeneration/metabolism/pathology

@article {pmid42334128,
year = {2026},
author = {Li, X and Wang, C and Duan, J and Shang, Q},
title = {Personalized Dosing System Guided by Cross-Scale Metabolic Imaging Biomarkers in Neovascular Age-Related Macular Degeneration.},
journal = {Translational vision science & technology},
volume = {15},
number = {6},
pages = {27},
doi = {10.1167/tvst.15.6.27},
pmid = {42334128},
issn = {2164-2591},
mesh = {Humans ; *Biomarkers/metabolism ; Female ; *Aqueous Humor/metabolism ; Retrospective Studies ; Male ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Aged ; *Precision Medicine/methods ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Metabolomics/methods ; Bevacizumab/administration & dosage ; *Wet Macular Degeneration/drug therapy/metabolism/diagnostic imaging ; Aged, 80 and over ; },
abstract = {PURPOSE: Long-term anti-vascular endothelial growth factor (VEGF) response in neovascular age-related macular degeneration (nvAMD) varies widely, with no validated predictive biomarkers. We aimed to establish a metabolic imaging biomarker-based framework for personalized efficacy prediction and dosing.

METHODS: In this single-center retrospective study, patients with clinically confirmed nvAMD and age-matched controls (cataract surgery with normal fundus or non-neovascular AMD) were enrolled. Aqueous humor was analyzed by ultra-high-performance liquid chromatography tandem mass spectrometry. Patients with nvAMD received anti-VEGF therapy (three doses then as needed, followed for ≥12 months) and were classified by structural/functional outcomes as responders or nonresponder. Comparative metabolomics identified phenotype-associated metabolites. An integrated prediction model was built using orthogonal partial least squares discriminant analysis, receiver operating characteristic analysis, and multivariate logistic regression.

RESULTS: The aqueous humor of patients with nvAMD showed lipid remodeling and suppressed purine metabolism. Eight key metabolites were identified as phenotype-associated biomarkers (indole-3-acetic acid, N-acetyl-L-alanine, xanthine, arachidonoyl lysophosphatidic acid, taurine, indole-3-lactic acid, 4-acetoxyphenol, and Lys-Ile). Among them, indole-3-acetic acid and N-acetyl-L-alanine showed the highest predictive performance for long-term treatment response (area under the curve = 0.802 each). Integrating metabolic markers with baseline imaging and clinical parameters improved predictive accuracy (area under the curve = 0.86). Longitudinal analysis showed partial normalization of metabolite levels in responders after anti-VEGF therapy.

CONCLUSIONS: nvAMD involves responder-specific metabolic reprogramming. Integrating aqueous metabolites with imaging biomarkers enables accurate pretreatment prediction of anti-VEGF efficacy, supporting personalized therapy.

TRANSLATIONAL RELEVANCE: This work links aqueous metabolic profiling to clinical decision-making by identifying biomarkers predictive of long-term anti-vascular endothelial growth factor response. Their integration with routine imaging yields a pretreatment stratification model (area under the curve = 0.86), which may inform individualized monitoring and earlier regimen adjustment in predicted nonresponders.},
}

Humans
*Biomarkers/metabolism
Female
*Aqueous Humor/metabolism
Retrospective Studies
Male
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
Aged
*Precision Medicine/methods
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Metabolomics/methods
Bevacizumab/administration & dosage
*Wet Macular Degeneration/drug therapy/metabolism/diagnostic imaging
Aged, 80 and over

@article {pmid42323663,
year = {2026},
author = {Shettigar, MP and Chhablani, J and Tyagi, M and Narula, R and Narayanan, R},
title = {Accuracy of Retinal Pigment Epithelium (RPE) undulations (Oscillatory sign) as an optical coherence tomography biomarker of acute RPE tears.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00874-7},
pmid = {42323663},
issn = {2056-9920},
abstract = {PURPOSE: To evaluate the sensitivity and specificity of Retinal Pigment Epithelium (RPE) undulations (Oscillatory sign) on Optical Coherence Tomography (OCT) and assess its potential role as a predictive OCT biomarker for RPE tears in eyes with neovascular age-related macular degeneration (nAMD).

METHODS: Retrospective analysis of the patients who had RPE tears following nAMD, which were documented by multimodal imaging. All cases were evaluated for RPE undulations on OCT, and the sensitivity and specificity of the Oscillatory sign in eyes with documented RPE tears were assessed.

RESULTS: Seventy-nine eyes out of 936 eyes with nAMD, which were analyzed, were found to have RPE tears, as documented by colour fundus photographs (CFP) and fundus autofluorescence (FAF). OCT images were analyzed for RPE undulations, a sign of oscillatory activity. Thirty-eight eyes of 79 (48.1%) eyes were found to have the oscillatory sign. Oscillatory sign showed a high specificity of 98.95% and sensitivity of 48.10% for an underlying RPE tear. The negative predictive value of the Oscillatory sign was 95.39%, and the positive predictive value of 80.85%.

CONCLUSION: The Oscillatory sign of RPE undulations is not sensitive, but it is a highly specific biomarker and can help facilitate the diagnosis of occult RPE tears.},
}

@article {pmid42323782,
year = {2026},
author = {Waisberg, E and Ong, J and Yaldo, L and Kumar, R and Wang, W and Calabresi, V and Coco, G and Gonzalez-Lima, F and Lee, AG and Giannaccare, G},
title = {Near-Infrared and Red-Light Photobiomodulation for Ocular Aging and Diseases: A Narrative Review.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42323782},
issn = {2193-8245},
abstract = {Near-infrared (NIR) and red light photobiomodulation (PBM) has gained increasing interest as a non-invasive therapeutic approach for a variety of medical conditions including ocular diseases. The eye represents a particularly suitable target for light-based therapies owing to its optical accessibility and the high mitochondrial demand of various tissues such as the retina and optic nerve. Ocular aging and several ophthalmic disorders are associated with mitochondrial dysfunction, oxidative stress, and chronic inflammation, providing a biological rationale for the use of PBM as a potential adjunctive approach. This narrative review provides an evidence-weighted, indication-specific synthesis of NIR and red-light PBM in ophthalmology, emphasizing device- and protocol-dependence, differences between multiwavelength PBM and repeated low-level red-light therapy, study-design limitations, safety considerations, and clinical translation gaps. A structured literature search was conducted using major scientific databases to identify relevant experimental studies, clinical trials, and observational reports. The review focuses on proposed mitochondria-centered mechanisms of action, including cytochrome c oxidase-mediated signaling, nitric oxide release, reactive oxygen species-driven hormetic responses, and downstream anti-inflammatory effects. Particular emphasis is reserved to dry age-related macular degeneration, for which literature is more relevant, and to dry eye disease owing to meibomian gland dysfunction and myopia, for which a body of evidence is progressively growing. For other ocular indications, data remain preliminary or exploratory. Overall, available data support biological plausibility and suggest possible functional or anatomical signals in selected ocular diseases, but the clinical evidence remains heterogeneous, with substantial variability in devices, wavelengths, dosimetry, treatment protocols, and study design, and remains insufficient to define PBM as established therapy for most indications. However, the clinical evidence remains heterogeneous, with substantial variability in devices, wavelengths, dosimetry, and treatment protocols. Although available studies generally report favorable short-term tolerability, long-term safety and the role of PBM in routine ophthalmic practice remain insufficiently defined. Well-designed, adequately randomized controlled trials with standardized treatment parameters are required to determine efficacy, optimal protocols, and long-term clinical relevance.},
}

@article {pmid42324318,
year = {2026},
author = {Pu, J and Ji, Y and Li, M and Zhang, X and Zuo, C and Zhuang, X and Hao, X and He, G and Gan, Y and Su, Y and Zhang, Y and Yang, R and Chen, X and Mi, L and Wen, F},
title = {Indocyanine green angiography and machine learning analysis determine topographic distribution of peripheral hard drusen in a Chinese cohort.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-026-01737-w},
pmid = {42324318},
issn = {2730-664X},
abstract = {BACKGROUND: Hard drusen appear as hyperfluorescent dots on indocyanine green angiography (ICGA) due to their high phospholipid content. This study aims to explore the distribution of peripheral hard drusen across age groups and retinal regions, and their correlation with macular pathology including hard drusen, soft drusen, and progression to neovascular age-related macular degeneration (nAMD).

METHODS: A hospital-based retrospective study was conducted at Zhongshan Ophthalmic Center. Patients who underwent ICGA over a five-year period were included and categorised into seven age groups. Hard drusen were quantified across nine retinal quadrants using the Trainable Weka Segmentation machine learning plugin. A subgroup of patients underwent imaging follow-up to assess progression to nAMD.

RESULTS: Here we show, across 1562 normal eyes (14,058 ICGA images) quantified using a validated machine learning model (Dice coefficient: 0.697; sensitivity: 82.93%; ICC: 0.944), that age 50 represents a critical threshold for drusen accumulation, with significant increases observed across all nine quadrants. The nasal quadrants demonstrate earlier and more prominent drusen accumulation compared to the temporal quadrants (P < 0.001 across ages 20-69 years). Notably, the central superior quadrant shows consistent associations with macular hard drusen counts (Stdβ = 0.104, P = 0.010), soft drusen volume (ρ = 0.657, P = 0.020), and progression to nAMD (OR = 1.324, P = 0.040).

CONCLUSIONS: Peripheral hard drusen accumulate preferentially in the nasal quadrants and increase markedly after age 50. Comprehensive peripheral retinal evaluation during ICGA examination may hold potential clinical value for AMD monitoring, pending further prospective validation.},
}

@article {pmid42324406,
year = {2026},
author = {Serra, R and Français, C and Boulet, JF and Pinna, A and Philippakis, E and Zambrowski, O and Mathis, T and Kodjikian, L and Coscas, F},
title = {Vascular remodeling of macular neovascularization following switch to intravitreal faricimab in neovascular AMD.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42324406},
issn = {1435-702X},
abstract = {PURPOSE: To describe qualitative optical coherence tomography angiography (OCTA) changes in age-related macular degeneration (AMD) macular neovascularization (MNV) treated with faricimab.

METHODS: This was a retrospective study including 30 eyes with active AMD-related Type 1 MNV, resistant to traditional anti-vascular endothelial growth factor (VEGF) agents, receiving intravitreal faricimab. Complete ophthalmological evaluation, consisting of best corrected visual acuity (BCVA), traditional multimodal imaging, and OCTA scans, was performed at baseline and at the last examination. OCTA high-flow networks corresponding to MNV were qualitatively and quantitatively analyzed to assess morphological changes. Furthermore, the correlation between MNV OCTA pattern and presence/absence of exudation signs on spectral domain OCT (SD-OCT) was evaluated.

RESULTS: On baseline OCTA, 11/30 eyes showed a sea fan pattern, 13/30 a medusa pattern, and the remaining 6/30 an indistinct pattern. At the last follow-up, in 12/30 eyes, the MNV pattern remained unchanged. In these 12 cases, SD-OCT revealed the exudative signs in 11/12 eyes (one with intra-retinal fluid, ten with sub-retinal fluid) at the final evaluation. In the remaining 18/30, MNV pattern changed to a dead tree type with no exudation signs at the last follow-up in 17/18 eyes. The mean interval of intravitreal injection was significantly extended from 4 to 7.2±2.3 weeks (p < 0.0001) with BCVA stabilization. At the last follow-up the dead tree OCTA pattern resulted to be significantly related to the absence of exudation sings (p < 0.0001).

CONCLUSION: Our study reveals that the initial MNV pattern frequently moves toward a dead tree pattern after switching from traditional anti-VEGF agents to faricimab therapy.},
}

@article {pmid42324407,
year = {2026},
author = {Sarao, V and Veritti, D and Lanzetta, P},
title = {Comment to: Hashiya N, Maruko I, Maruko R et al. Increased intraocular pressure immediately after aflibercept 8 mg intravitreal injection for neovascular age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol (2026) 264:1611-1617. doi:10.1007/s00417-026-07117-3.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42324407},
issn = {1435-702X},
}

@article {pmid42326286,
year = {2026},
author = {Orozco Loaiza, G and Alfaro Guerra, MJ and Murillo Sotela, A and Villalobos Villalobos, P},
title = {Complement Inhibition in Geographic Atrophy: Clinical Evidence for Pegcetacoplan and Avacincaptad Pegol.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e109282},
pmid = {42326286},
issn = {2168-8184},
abstract = {Geographic atrophy (GA) represents the advanced form of non-neovascular age-related macular degeneration (AMD) and is associated with progressive and irreversible vision loss. Evidence has implicated the dysregulation of the complement cascade as a pivotal factor in GA pathophysiology, leading to the development of complement inhibition therapies. Pegcetacoplan, a C3 inhibitor, and avacincaptad pegol, a C5 inhibitor, are currently the only therapies approved by the Food and Drug Administration (FDA) for GA secondary to AMD. Major clinical trials, including OAKS, DERBY, GALE, GATHER1, and GATHER2, have demonstrated a statistically significant reduction in GA lesion area, with reductions of approximately 16-22% for pegcetacoplan and 14-28% for avacincaptad pegol compared with sham. Despite favorable structural outcomes, functional endpoints like best-corrected visual acuity (BCVA) and low-luminance visual acuity (LLVA) have shown limited improvement, and concerns remain regarding their side effect profile. This narrative review provides an overview of GA, emphasizing its pathophysiology and the role of the complement cascade, and discusses the clinical relevance of complement inhibitors in the current management of the disease.},
}

@article {pmid42326551,
year = {2026},
author = {Ariza-Torrado, IP and Groman-Lupa, S and Martínez-Córdoba, CJ and Monje-Tobar, P},
title = {Evaluation of Structural and Functional Outcomes After the Application of an Initial Single Dose of Faricimab.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261451498},
pmid = {42326551},
issn = {2474-1272},
abstract = {Purpose: To evaluate functional and structural outcomes after application of a single intravitreal dose of faricimab in patients with chronic retinal diseases. Methods: In this observational, longitudinal, prospective study, best-corrected visual acuity (BCVA) and central macular thickness (CMT) were evaluated before and 4, 8, 12, and 16 weeks after a single dose of intravitreal faricimab. Results: A total of 49 eyes of 41 patients were included, of which 28 were treatment-naive eyes (had not previously received intravitreal therapy) and 21 were eyes in which a switch from a previous antiangiogenic agent was indicated. The main diagnoses were diabetic macular edema in 63.3% (31 eyes) and age-related macular degeneration in 24.5% (12 eyes). Ten eyes (20.4%) required additional antiangiogenic injections due to worsening or only partial improvement in CMT, whereas ~58% of eyes completing follow-up did not require further treatment and maintained anatomic improvement on optical coherence tomography throughout the study period. At 4 weeks after initial injection, CMT was reduced a mean 117.5 µm. Statistically significant decreases were maintained over 8, 12, and 16 weeks. In treatment-naive eyes, initial mean reduction in CMT was 119.7 µm, with sustained decreases at all time points, while in the treatment-switch group, initial mean reduction in CMT was 114.6 µm, with sustained decreases at weeks 4 and 8, but not at weeks 12 and 16. In the general sample, 53.1% to 61.0% of eyes demonstrated clinically modest improvements in BCVA, equivalent to 1 to 2 Early Treatment Diabetic Retinopathy Study lines of vision, but visual changes were not statistically significant. Conclusions: Clinically meaningful reductions in CMT were observed and sustained over the 16-week follow-up after a single intravitreal faricimab injection. Notably, a substantial proportion of eyes did not require additional antiangiogenic treatment during follow-up, suggesting that mandatory loading doses may not be universally required to achieve short-term anatomic benefit in selected patients. However, functional gains were modest and did not reach statistical significance, underscoring that anatomic improvement does not necessarily translate into meaningful visual recovery. These findings highlight the importance of individualized dosing strategies in real-world clinical practice and suggest potential implications for reducing treatment burden, costs, and barriers to access in eligible patients.},
}

@article {pmid42328256,
year = {2026},
author = {Sukumaran, D and Benjamin, D and Abdul Karim, MN and Amankwah, R and Maharajan, P and Mubashar, M and Sarmad, A and Sharma, P and Dhar-Munshi, S},
title = {Real-World Functional and Anatomical Outcomes of Intravitreal Faricimab in Suboptimal Responders With Neovascular Age-Related Macular Degeneration: A 24-Month Clinical Audit.},
journal = {Cureus},
volume = {18},
number = {6},
pages = {e111161},
pmid = {42328256},
issn = {2168-8184},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) is a chronic sight-threatening disease requiring repeated intravitreal antivascular endothelial growth factor (anti-VEGF) injections. Although established anti-VEGF agents have transformed the prognosis of nAMD, a proportion of patients demonstrate persistent exudation, limited durability, or inability to extend beyond short treatment intervals. Faricimab is a bispecific intravitreal antibody targeting both vascular endothelial growth factor A and angiopoietin-2, designed to improve vascular stability, reduce exudation, and increase treatment durability. This clinical audit evaluates 24-month real-world outcomes following switching to faricimab in suboptimal responders with nAMD in an NHS medical retina service.

METHODS: A retrospective clinical audit was conducted of 274 eyes with nAMD switched to faricimab at Sherwood Forest Hospitals NHS Foundation Trust between January 2023 and January 2025. All eyes had previously received at least one anti-VEGF agent and were switched because of persistent disease activity, inadequate anatomical response, or high treatment burden. Data were extracted from the Medisight electronic patient record and cross-checked against pharmacy records. Primary outcomes were best corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters and central macular thickness (CMT) on optical coherence tomography. Secondary outcomes included injection interval extension, number of injections, and safety events.

RESULTS: Baseline mean BCVA was 58.1 letters. Mean BCVA improved to 59.7 letters at less than six months, representing a gain of +1.6 letters. At 12 months, mean BCVA was 56.9 letters, a change of -1.2 letters from baseline. At 24 months, mean BCVA was 54.4 letters, a change of -3.7 letters from baseline. Anatomical response was more consistent, with mean CMT reductions of -29.1 µm at less than six months, -34.7 µm at 12 months, and -45.7 µm at 24 months. The mean injection interval increased from 7.88 weeks before switching to 10.67 weeks after switching, representing an extension of +2.79 weeks. No cases of intraocular inflammation, retinal vasculitis, or endophthalmitis were recorded.

CONCLUSION: In this real-world NHS audit, faricimab achieved meaningful anatomical improvement and reduced treatment burden in treatment-experienced nAMD eyes switched because of suboptimal response or limited durability on previous anti-VEGF therapy. Visual acuity improved modestly during early follow-up but declined slightly over 24 months, despite progressive anatomical drying. This functional-anatomical dissociation likely reflects the chronicity of disease and irreversible macular damage in a switch population. Faricimab appears to be a safe and effective second-line option for reducing exudation and extending treatment intervals, although expectations regarding long-term visual gain should be realistic.},
}

@article {pmid42328840,
year = {2026},
author = {Xavier, C and Toutée, A and Sales de Gauzy, T and March de Ribot, F and Forte, PA and Bodaghi, B and Bousquet, E and Touhami, S},
title = {Bilateral Giant Pigment Epithelial Detachments and Unilateral RPE Tear and Exudative Retinal Detachment After Tadalafil Exposure: Case Report and Review of the Literature.},
journal = {Retinal cases & brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001947},
pmid = {42328840},
issn = {1937-1578},
abstract = {PURPOSE: To describe a case of bilateral giant pigment epithelial detachments (PEDs) complicated by unilateral giant retinal pigment epithelium (RPE) tear and macula-off exudative retinal detachment (RD) in the context of tadalafil exposure, and to place it in the spectrum of reported non-AMD giant RPE tears.

METHODS: Case report with multimodal imaging and comprehensive systemic work-up, combined with a focused literature review of exudative RD associated with giant RPE tears unrelated to age-related macular degeneration.

RESULTS: A 62-year-old man presented with blurred vision in the left eye. Examination revealed bilateral giant temporal PEDs and, in the left eye, a crescent-shaped giant RPE tear contiguous with an inferior macula-off exudative RD and bilateral pachychoroid on OCT. Extensive systemic and ocular investigations were unremarkable except for regular tadalafil use. Discontinuation of tadalafil led to rapid resolution of subretinal fluid and improvement of BCVA to 20/25 OS at one year, whereas re-exposure triggered recurrence of serous macular detachment. Using the Naranjo scale, the causal relationship between tadalafil and the ocular event was rated as "certain". Literature review identified 33 published patients (43 eyes) with exudative RD and giant RPE tears without AMD, most commonly associated with bullous CSC and other pachychoroid entities.

CONCLUSION: Bilateral giant PEDs with unilateral giant RPE tear and macula-off exudative RD can occur in the setting of tadalafil-associated bullous CSC. This case underscores the importance of systematically reviewing systemic medications, including phosphodiesterase-5 inhibitors, in patients with atypical serous retinal detachments and RPE tears.},
}

@article {pmid42329076,
year = {2026},
author = {Zhang, R and Jin, A and Fan, X and Li, F and Feng, Y and Zeng, L and Wang, J and Fan, N and Niu, L and Liu, D},
title = {Accelerometer-Derived Moderate-to-Vigorous Physical Activity and the Risk of Four Common Vision-Threatening Ocular Diseases.},
journal = {Translational vision science & technology},
volume = {15},
number = {6},
pages = {24},
doi = {10.1167/tvst.15.6.24},
pmid = {42329076},
issn = {2164-2591},
mesh = {Humans ; Female ; Aged ; *Accelerometry ; Male ; *Exercise/physiology ; Risk Factors ; *Cataract/epidemiology ; Middle Aged ; *Glaucoma/epidemiology ; Proportional Hazards Models ; *Eye Diseases/epidemiology ; United Kingdom/epidemiology ; *Diabetic Retinopathy/epidemiology ; Follow-Up Studies ; Incidence ; *Macular Degeneration/epidemiology ; },
abstract = {PURPOSE: The purpose of this study was to investigate the association between accelerometer-derived moderate-to-vigorous physical activity (MVPA) and four common vision-threatening ocular diseases: cataract, diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma.

METHODS: A total of 77,644 UK Biobank participants with accelerometer-derived MVPA data were included. MVPA was categorized into three groups following World Health Organization (WHO) guidelines (<150, 150-299, and ≥300 min/week). Incident cataract, DR, AMD, and glaucoma were identified from linked hospital and primary care records. Restricted cubic splines and Cox proportional hazards models were used to estimate hazard ratios (HRs). Mediation analysis was performed to explore potential mechanisms.

RESULTS: During a median follow-up of 6.2 years, 4283 cataract, 248 DR, 891 AMD, and 762 glaucoma events occurred. We identified an L-shaped association for cataract and a nonlinear association for DR (both P < 0.001; P < 0.05 for nonlinearity), a modest negative association for AMD (P = 0.028; P = 0.026 for nonlinearity), and no significant association for glaucoma. Compared with the reference group (<150 min/week), the groups achieving 150-299 min/week and ≥300 min/week of MVPA exhibited significantly lower risks of cataract (HR = 0.91, 95% confidence interval [CI] = 0.84-0.98 for 150-299 min/week; and HR = 0.88, 95% CI = 0.82-0.95 for ≥300 min/week), and DR (HR = 0.62, 95% CI = 0.45-0.86 for 150-299 min/week; and HR = 0.51, 95% CI = 0.37-0.71 for ≥300 min/week). Mediation analysis indicated that inflammatory and metabolic indicators partially mediated the protective effect of MVPA on DR.

CONCLUSIONS: Higher levels of MVPA were associated with significantly lower risks of cataract and DR, with partial mediation through inflammatory and metabolic pathways for DR.

TRANSLATIONAL RELEVANCE: Our findings highlight MVPA as a potentially modifiable behavioral factor for ocular disease prevention.},
}

Humans
Female
Aged
*Accelerometry
Male
*Exercise/physiology
Risk Factors
*Cataract/epidemiology
Middle Aged
*Glaucoma/epidemiology
Proportional Hazards Models
*Eye Diseases/epidemiology
United Kingdom/epidemiology
*Diabetic Retinopathy/epidemiology
Follow-Up Studies
Incidence
*Macular Degeneration/epidemiology

@article {pmid42330208,
year = {2026},
author = {Ramachandran, ON and Talwar, D and Khare, G and Verma, L and Jena, S and Singh, S and Singh, K},
title = {Real-world efficacy of higher-dose aflibercept in pro-re-nata dosing without loading phases: A cost-effective approach for resource-limited settings.},
journal = {Indian journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.4103/IJO.IJO_2483_25},
pmid = {42330208},
issn = {1998-3689},
abstract = {BACKGROUND: Aflibercept therapy for chronic macular diseases mandates loading dose phases followed by fixed intervals, placing a heavy and often prohibitive treatment burden on elderly patients in resource-limited settings. We evaluated the real-world efficacy of higher-dose aflibercept (4 mg/0.1 mL) versus standard dose (2 mg/0.05 mL) using immediate modified pro-re-nata (PRN) dosing without loading phases, with specific focus on burden reduction while maintaining therapeutic outcomes.

METHODS: This retrospective comparative study included 194 eyes (101 receiving 4 mg/0.1 mL, 93 receiving 2 mg/0.05 mL) with diabetic macular edema, neovascular age-related macular degeneration, and retinal vein occlusion treated with immediate modified PRN aflibercept between October 2023 and September 2024. The primary outcomes were best-corrected visual acuity (BCVA) and central macular thickness (CMT). Secondary outcomes assessed injection intervals, visit frequency, caregiver accompaniment, time commitments, and safety.

RESULTS: The mean baseline BCVA was 0.55 ± 0.18 logMAR (4 mg group) and 0.54 ± 0.17 logMAR (2 mg group). At final follow-up, both groups achieved comparable improvement: 0.45 ± 0.15 logMAR (4 mg) versus 0.47 ± 0.16 logMAR (2 mg), with no significant difference between groups (P = 0.23). The mean CMT reduction was 85.2 ± 45.8 μm (4 mg) versus 86.6 ± 48.2 μm (2 mg), P = 0.82. The 4 mg group recorded 22.6% fewer annual visits (4.8 versus 6.2, P < 0.001), translating to 8.52 fewer hours per patient per year. No safety concerns emerged with higher-dose extraction.

CONCLUSION: Higher-dose aflibercept with immediate modified PRN dosing achieves visual and anatomical outcomes comparable to standard dosing, with a 22.6% reduction in annual visit frequency. This approach addresses practical barriers to care in elderly populations requiring long-term anti-VEGF therapy in resource-limited settings.},
}

@article {pmid42317230,
year = {2026},
author = {Örnek, K and Erşekerci, TK},
title = {Streptococcus salivarius endophthalmitis and corneal ring infiltrate after intravitreal bevacizumab injection.},
journal = {GMS ophthalmology cases},
volume = {16},
number = {},
pages = {Doc06},
pmid = {42317230},
issn = {2193-1496},
abstract = {A 65-year-old male patient received intravitreal bevacizumab for age-related macular degeneration. On the first day, he presented with ocular pain, corneal stromal infiltration and dense vitritis. Prompt intravitreal vancomycin and ceftazidime were injected after sampling. Widespread gram-positive cocci were seen on microscopy after staining the vitreous sample. No significant improvement took place the following day and the cornea was completely opacified. The patient underwent an early vitrectomy combined with penetrating keratoplasty. Culture grew Streptococcus salivarius. Postoperative visual acuity was hand motions and the retina was attached.},
}

@article {pmid42318308,
year = {2026},
author = {Yu, C and Dong, L and Zhang, R and Li, H and Shi, X and Wu, H and Zhou, W and Li, Y and Wei, WB},
title = {Causal Effects of Gut Microbiota and Associated Metabolites on Retinal Diseases and Visual Impairment: A Mendelian Randomization Study.},
journal = {Journal of ophthalmology},
volume = {2026},
number = {},
pages = {4233490},
pmid = {42318308},
issn = {2090-004X},
abstract = {BACKGROUND: Previous observational study findings have indicated a vital association between gut microbiota features and retinal diseases based on the "gut-retina" axis. However, whether their relationships underlie causal effects remains to be established.

METHODS: Instrumental variables of 211 gut microbiota taxa were obtained from a genome-wide association study (GWAS), and 28 gut-associated metabolites and pathways were included as exposures. A two-sample Mendelian randomization (MR) study was carried out to estimate gut microbiota effects on diabetic retinopathy (DR), early age-related macular degeneration (eAMD), retinal detachments and breaks (RDs/RBs), retinal vascular occlusion (RVO), disorders of the choroid and retina (D-C/R), and visual impairment. MR methods, including inverse variance weighted (IVW), MR‒Egger, weighted median, simple mode, and weighted mode methods, were used to investigate the causal relationship between gut microbiota features and various outcomes. Heterogeneity, pleiotropy, and stability tests of MR results were performed, and Bonferroni's correction was used to test the strength of the causal relationships between exposures and outcomes, as well as reverse and multivariable MR analyses.

RESULTS: Through MR analysis of 211 microbes and six clinical phenotypes, a total of 35 gut microbiome and 3 associated metabolites were found to be associated with various outcomes. Cochrane's Q test revealed that there was no significant heterogeneity between various single-nucleotide polymorphisms. In addition, no significant level of pleiotropy was found according to the MR‒Egger and MR-PRESSO global tests. After the Bonferroni-corrected test, Genus id.2041 (OR = 0.874, 95% CI: 0.816-0.936, p = 1.10e - 04, IVW) showed robust causality with D-C/R, which had a nominal association with multiple other retinal diseases as well. Seven exposure-outcome effects markedly remained valid when BMI or alcohol intake frequency was separately included in multivariable MR analyses. According to the results of reverse MR analysis, no significant causal effect of outcomes was found on gut microbiota. No significant heterogeneity of instrumental variables or horizontal pleiotropy was found.

CONCLUSION: We confirmed a potential causal relationship between some gut microbiota features and retinal diseases, thus providing new insights into the gut microbiota-mediated mechanism of retinopathy and indicating vital biomarkers for potential diagnostic, therapeutic, and prevention strategies.},
}

@article {pmid42320872,
year = {2026},
author = {Wang, L and Zhang, C and Li, N and Zhang, J and Liu, Y and Xu, G},
title = {Research Advances in Claudin-1 in the Eye.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111132},
doi = {10.1016/j.exer.2026.111132},
pmid = {42320872},
issn = {1096-0007},
abstract = {Claudin-1, a transmembrane protein integral to tight junctions, is indispensable for paracellular barrier formation and the establishment and maintenance of cellular polarity. In the eye, claudin-1 exhibits tissue-specific expression in critical structures such as the cornea and retina, where it contributes fundamentally to corneal transparency, blood-retinal barrier integrity, and retinal homeostasis. This review comprehensively synthesizes current knowledge on the spatial distribution and physiological roles of claudin-1 across ocular tissues. We critically evaluate recent mechanistic and translational advances implicating claudin-1 dysregulation in a spectrum of ocular pathologies: anterior segment disorders (dry eye disease, pterygium, infectious keratitis, and gelatinous drop-like corneal dystrophy), retinal diseases (diabetic retinopathy, age-related macular degeneration, central serous chorioretinopathy, and retinoblastoma), and other conditions (uveitis, glaucoma, post-cataract macular edema, and cataract). Finally, we assess the emerging therapeutic potential of claudin-1-both as a molecular target for barrier modulation and as a facilitator of paracellular drug delivery in ophthalmology.},
}

@article {pmid42321202,
year = {2026},
author = {Rajala, A and Rajala, R and Trevino, LJ and Black, TM and Moiseyev, G and Kinter, M and Rajala, RVS},
title = {Interdependent roles of PKM2 in photoreceptors and RPE: implications for retinal degeneration.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-026-08997-3},
pmid = {42321202},
issn = {2041-4889},
support = {EY035282//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; EY021725//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; },
abstract = {Pyruvate kinase M2 (PKM2) functions as both a glycolytic enzyme and a transcriptional co-activator that coordinates metabolism and cell survival. Here, we define the developmental timing, cellular distribution, and physiological role of PKM isoforms in the mouse retina. PKM2 expression begins at postnatal day 2, preceding PKM1, and is highly enriched in photoreceptors, whereas PKM1 predominates in retinal ganglion cells. Conditional deletion of PKM2 in the retina, rods, or retinal pigment epithelium (RPE) demonstrated that PKM2 is essential for maintaining retinal structure and function. Loss of PKM2 impaired glycolytic activity, decreased ATP generation, and disrupted metabolic balance, leading to cellular disorganization and degeneration in both photoreceptors and the RPE. In the RPE, PKM2 deficiency decreased RPE65 protein levels and impaired the regeneration of 11-cis-retinal, disrupting the visual cycle. PKM2 deletion disrupted the normal cone opsin gradient, indicating that PKM2-dependent metabolic and transcriptional functions are essential for maintaining proper cone organization in the retina. Moreover, rod-specific deletion of PKM2 in Abca4 mutant mice showed early signs of retinal degeneration. The studies described in this manuscript highlight the interdependence of photoreceptor and RPE metabolism and show that PKM2 plays an important role in retinal energy homeostasis and neuronal survival, providing insight into the mechanisms underlying photoreceptor and RPE degeneration in age-related macular degeneration.},
}

@article {pmid42321514,
year = {2026},
author = {Huang, J and Nittala, MG and Corradetti, G and Chung, YC and Quarta, A and Abbasgholizadeh, R and Soylu, C and Chujo, S and Velaga, SB and Sadda, SR},
title = {Spatial distribution of cuticular drusen and its association with category-specific progression risk in intermediate AMD.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42321514},
issn = {1476-5454},
support = {RO1EY023164//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; 1R01EY030614//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; RO1EY023164//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; 1R01EY030614//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; },
abstract = {OBJECTIVES: To investigate the spatial distribution pattern of cuticular drusen using en face OCT and determine its relationship with 2-year progression of age-related macular degeneration (AMD).

METHODS: This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enroled in the Amish Eye Study who completed two years of follow-up. Multimodal imaging, including volume spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three Early Treatment Diabetic Retinopathy Study (ETDRS) grid zones using ImageJ. K-means clustering analysis was used to categorize distribution patterns. Firth's penalized logistic regression evaluated association between cuticular drusen distribution categories and progression to late AMD at 2 years.

RESULTS: Three spatial phenotypes of cuticular drusen were identified: central-dominant (57.5%), outer-macular-dominant (32.2%), and diffuse (10.3%). Over two years, five eyes progressed to late AMD, four of which belonged to the outer-macular-dominant group. In unadjusted Firth regression, the outer-macular-dominant phenotype was associated with higher odds of progression than the other phenotypes (OR 7.16; 95% CI 1.24-74.20, p = 0.027). After adjustment for subretinal drusenoid deposits (SDDs) and large drusen, the association between spatial phenotype and progression remained (OR 11.53; 95% CI 1.62-169.00; p = 0.013), while SDDs were also associated with progression (OR 9.26; 95% CI 1.36-78.65; p = 0.023).

CONCLUSIONS: Clustering of en face OCT-derived spatial features identified distinct cuticular drusen phenotypes within the macula. The outer-macular-dominant phenotype may be associated with an increased likelihood of AMD progression in this exploratory analysis.},
}

@article {pmid42322415,
year = {2026},
author = {Chujo, S and Quarta, A and Abbasgholizadeh, R and Chung, YC and Kwak, H and Soylu, C and Alhelaly, M and Rattu, R and Huang, J and Corradetti, G and Velaga, S and Nittala, MG and Uji, A and Sadda, SR},
title = {Development of a conceptual, HOV-inspired spatial weighting model for quantifying geographic atrophy severity.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42322415},
issn = {1435-702X},
abstract = {PURPOSE: To develop a Hill of Vision (HOV)-inspired severity score for geographic atrophy (GA) and evaluate its ability to capture spatial characteristics of disease progression, including lesion location and proximity to the foveal center, compared with the conventional lesion area (ΔArea) metric.

METHODS: This retrospective analysis included 103 untreated fellow eyes from the MAHALO study with fundus autofluorescence images available at all visits. GA lesions were delineated and binarized to generate mask images. A Gaussian weighting function based on the distance from the foveal center was applied to each lesion pixel to model the spatial distribution of retinal functional resolution, yielding a volumetric "severity score," that was kept unitless for the purpose of this exercise. For eyes with multifocal GA, total severity was defined as the sum of all lesion values. The correlation between ΔArea and ΔSeverity (0-18 months) was assessed using Pearson's coefficient. Lesion expansion direction was visualized using Euclidean distance maps.

RESULTS: Mean changes in ΔArea and ΔSeverity over 18 months were 1.02 ± 1.11 mm² and 5811 ± 4584, respectively. A weak but significant correlation was observed (r = 0.36, p < 0.01). Cases with peripheral enlargement showed modest severity increases, whereas parafoveal expansion caused steep severity rises despite relatively minimal area growth. Expansion maps revealed that the direction and expansion to the fovea strongly influenced severity progression.

CONCLUSIONS: The HOV-inspired severity score provides a spatially weighted framework for assessing GA progression and may complement conventional structural metrics by incorporating lesion location relative to the fovea.},
}

@article {pmid42323420,
year = {2026},
author = {Zhang, Y and Gao, J and Zhou, A and Wang, J},
title = {Optical coherence tomography angiography imaging characteristics and clinical significance of the foveal vertical hyperreflective line in patients with macular neovascularisation.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42323420},
issn = {1476-5454},
support = {82501291//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {BACKGROUND: To investigate the incidence, characteristic manifestations, outcomes of changes, and potential clinical significance of the foveal vertical hyperreflective line (FVHL) on optical coherence tomography angiography (OCTA) in patients with macular neovascularisation (MNV).

METHODS: This retrospective observational case series was conducted using OCTA images, fundus photographs, best-corrected visual acuity measurements, and other clinical information of the eyes of patients with MNV who were followed up for at least 3 months between January 2024 and October 2025. The incidence of FVHLs, OCTA characteristics, FVHL changes, and prognoses were analysed.

RESULTS: Among the 322 eyes of 161 patients with MNV, 14 patients (8.7%) showed FVHLs in 15 eyes. The mean age of the patients was 69.29 ± 12.68 years. Among the eyes with an FVHL, 13 were of patients with age-related macular degeneration-MNV and two were of patients with pathological myopia-MNV. All cases showing FVHLs occurred in the early stages of the disease course (within 1-3 months) and did not disappear during follow-up. Among the cases with FVHLs, 80% showed no obvious changes in the FVHLs and 20% showed weakened reflexes. The eyes that showed FVHL maintenance had a higher interdigitation zone/ellipsoid zone (IZ/EZ) repair rate (91.7%) than those with reflex-weakened FVHLs (p = 0.009).

CONCLUSIONS: FVHLs were present in 8.7% of patients with MNV. The eyes that maintained FVHLs exhibited a higher degree of IZ/EZ restoration than the eyes with reflex-weakened FVHLs. This OCTA finding may provide a foundation for assessing the recovery responses of retinal photoreceptors and Müller cells.},
}

@article {pmid42323551,
year = {2026},
author = {Lan, L and Lan, J and Ren, X and Ye, B},
title = {Impact of a structured patient engagement program on treatment adherence, injection persistence, and visual outcomes in real-world anti-VEGF therapy for neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-05045-8},
pmid = {42323551},
issn = {1471-2415},
abstract = {BACKGROUND: Neovascular age-related macular degeneration (nAMD) is a leading cause of irreversible visual impairment among older adults. Although intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has improved visual outcomes, real-world effectiveness is often limited by poor adherence and treatment discontinuation. This study evaluated the impact of a structured patient engagement program on treatment adherence, injection persistence, visual outcomes, and patient-reported outcomes in patients receiving anti-VEGF therapy for nAMD.

METHODS: This single-center retrospective observational comparative cohort study included 350 patients with nAMD treated between January 2022 and December 2024. Patients received either standard care alone (n = 175) or standard care plus a structured patient engagement program (n = 175) incorporating individualized education, adherence counseling, appointment reminders, and proactive follow-up communication. Primary outcomes were treatment adherence and injection persistence. Secondary outcomes included best-corrected visual acuity (BCVA), patient satisfaction, and disease understanding.

RESULTS: Patients enrolled in the engagement program demonstrated significantly better adherence than those receiving standard care. The mean number of missed injection visits was lower (0.51 ± 0.68 vs. 1.48 ± 1.27; P < 0.001), and delayed injections exceeding two weeks were less frequent (22.3% vs. 50.9%; P < 0.001). Good adherence was achieved in 89.1% of patients in the engagement group compared with 50.3% in the standard care group (P < 0.001), while treatment persistence was higher (90.9% vs. 77.7%; P = 0.001). Final BCVA was significantly better in the engagement group (0.61 ± 0.30 vs. 0.70 ± 0.34 LogMAR; P = 0.015), and a greater proportion of patients experienced visual improvement (65.1% vs. 52.6%; P = 0.023). Patient satisfaction and disease understanding were also significantly higher among patients receiving the engagement intervention (P < 0.001 for both). Safety outcomes were comparable between groups.

CONCLUSIONS: A structured patient engagement program was associated with improved treatment adherence, enhanced injection persistence, and better short- to mid-term visual outcomes in patients receiving anti-VEGF therapy for nAMD. These findings support the integration of patient-centered engagement strategies into routine retinal care to optimize real-world treatment outcomes.},
}

@article {pmid42314011,
year = {2026},
author = {Saravia, MJ and Rojas, J and de Los Santos, C and Bazterrechea, P and Forgues, F and Monteros, N and Cortalezzi, JM and Zeolite, I and Sgattoni, E and Zeman, L and Vidosevich, M and Magnano, G and Zas, M and Rosendi, E and Franco, J and Calhoun, MW and Wilbur, LR and Rosenfeld, PJ and Lylyk, P},
title = {Feasibility Study of Balloon Angioplasty for the Treatment of Ophthalmic Artery Stenoses in Patients With Geographic Atrophy.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/23258160-20260527-01},
pmid = {42314011},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: A safety and feasibility study was conducted using balloon angioplasty to treat ophthalmic artery (OA) stenoses in patients with age-related macular degeneration (AMD) with geographic atrophy (GA).

PATIENTS AND METHODS: Patients ≥ 60 years of age received OA angioplasty using an investigational catheter system and were followed for 6 months. Changes in stenosis, best-corrected visual acuity (BCVA), MNRead acuity charts, ophthalmic imaging, and a validated questionnaire were evaluated.

RESULTS: Eleven patients were treated. All adverse events were treated as needed and resolved without sequelae. Treated patients demonstrated a mean improvement over baseline in BCVA (P = .01) and reading speed (P = .03) at study exit. Mean subfoveal choroidal thickness increased over baseline (P = .004) and fellow eyes (P = .03) through week 4, remaining above baseline at study exit. Participants reported mean improvements in both mobility and reading.

CONCLUSION: Treating OA stenoses using angioplasty in patients with GA was safe with apparent visual function benefit.},
}

@article {pmid42314743,
year = {2026},
author = {Volle, DC},
title = {New-Onset Visual Snow Syndrome Following Prescription of Bupropion in a Patient With Macular Degeneration and Geographic Atrophy.},
journal = {The primary care companion for CNS disorders},
volume = {28},
number = {3},
pages = {},
doi = {10.4088/PCC.25cr04169},
pmid = {42314743},
issn = {2155-7780},
}

@article {pmid42314988,
year = {2026},
author = {Lu, H and Rakoski, AI and Ri, K and Zhou, L and Shi, L and Cho, H and Wu, S and Chen, SS and Neill, AN and Catazaro, J and Wong, VW and Yoo, A and Wilson, DS and Doloff, JC and Duh, EJ},
title = {Intraocular delivery of crystalline sorafenib provides sustained, potent inhibition of wet age-related macular degeneration.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {115120},
doi = {10.1016/j.jconrel.2026.115120},
pmid = {42314988},
issn = {1873-4995},
abstract = {Neovascular age-related macular degeneration (nAMD) is a leading cause of blindness worldwide. Anti-VEGF agents are very beneficial for nAMD, with intravitreal (IVT) delivery becoming the gold standard for treatment of nAMD and other retinal conditions. Incomplete response remains a major challenge, as does the requirement for high-frequency, repeat IVT injections, which pose a significant burden on patients. Many potential drug candidates have attractive pharmacodynamic profiles but are limited by their insolubility, precluding IVT administration. These include tyrosine kinase inhibitors (TKIs), which target multiple receptors regulating angiogenesis, including the VEGF receptors. Thus, there is a great need for alternative treatment approaches. To this end, we developed a crystallization formulation approach for sorafenib (SFB), a very hydrophobic anti-angiogenic, multi-receptor TKI, for sustained intraocular release. We evaluated the efficacy of this formulation in two mouse models of nAMD: laser-induced choroidal neovascularization (LI-CNV) and Vldlr knockout (Vldlr-/-). Crystalline sorafenib ("Crystal SFB") exhibited controlled, prolonged drug release across both an accelerated release assay in vitro and in C57BL/6 mice, with ~13% remaining in the eye after 28 days in vivo. Further, a single IVT injection effectively suppressed both neovascularization and vascular leakage, two critical clinical parameters in nAMD, for at least 28 days. IVT administration of Crystal SFB did not have discernible adverse effects on intraocular pressure, retinal morphology assessed by OCT, or neuroretinal function as measured by ERG. These results suggest that Crystal SFB offers a promising alternative for long-term nAMD management and a proof-of-concept for ocular utilization of other crystallized drugs.},
}

@article {pmid42315290,
year = {2026},
author = {Jackson, TL and Desai, R and Wafa, HA and Lee, CN and Wang, Y and Peacock, JL and Peto, T and Chakravarthy, U and Zhu, X and Dakin, H and Wordsworth, S and Clinch, P and Ramazzotto, L and Neffendorf, JE and O'Sullivan, JM and Reeves, BC and , },
title = {Stereotactic radiotherapy for neovascular age related macular degeneration: year 3 and 4 extended follow up results of a randomised, double masked, sham controlled, device trial (STAR).},
journal = {BMJ (Clinical research ed.)},
volume = {393},
number = {},
pages = {e729694},
doi = {10.1136/bmj-2026-729694},
pmid = {42315290},
issn = {1756-1833},
mesh = {Humans ; Female ; Double-Blind Method ; Visual Acuity ; Male ; Follow-Up Studies ; Treatment Outcome ; Aged ; *Radiosurgery/methods/adverse effects ; *Wet Macular Degeneration/drug therapy/radiotherapy ; Angiogenesis Inhibitors/therapeutic use/administration & dosage ; Middle Aged ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Aged, 80 and over ; *Macular Degeneration ; },
abstract = {OBJECTIVE: To assess the effects of stereotactic radiotherapy (SRT) for neovascular age related macular degeneration (AMD) beyond the two year primary outcome of the StereoTactic radiotherapy for wet Age-Related macular degeneration (STAR) trial.

DESIGN: Randomised, double masked, sham controlled, device trial involving preplanned recall from standard care.

SETTING: 30 NHS hospitals in the UK.

PARTICIPANTS: 411 participants aged at least 50 years with chronic, pretreated, active AMD.

INTERVENTION: Participants received one-off 16 Gray SRT or sham SRT delivered using a robotically controlled device. After two years of monthly study visits, participants reverted to routine care, with anti-VEGF drug selection and dosing intervals based on local practice, but with masking maintained, and repeat data collection at years 3 and 4 study visits.

MAIN OUTCOME MEASURES: The main efficacy outcome at year 4 was the number of anti-VEGF injections, tested for superiority (fewer injections). The other main outcome was visual acuity, tested for non-inferiority (five letter margin). Safety outcomes included adverse events, serious adverse events, and microvascular abnormalities. The same analyses were undertaken at years 2, 3, and 4. A within trial costing analysis was undertaken for participants with four years' follow-up.

RESULTS: Of 411 participants (204 (58%) women), 274 were allocated to SRT and 137 to sham SRT. The year 4 intention-to-treat efficacy analysis included 222 (81%) participants in the SRT group and 106 (77%) in the sham SRT group. The SRT group received a mean of 19.1 (standard deviation 10.9) injections over four years versus 21.6 (11.3) with sham SRT, an adjusted decrease of 3.2 injections (95% confidence interval (CI) of difference -5.7 to -0.7). During years 3 and 4, the SRT group received a mean cumulative 8.4 injections versus 8.3 injections in the sham SRT group. The final change in visual acuity in the SRT group was 8.3 letters worse than in the sham group (95% CI of difference -12.7 to -4.0). Adverse event rates were similar between groups, but reading centre-detected microvascular abnormalities occurred in 126/218 SRT treated eyes (58%) and 16/102 (16%) sham SRT treated eyes.

CONCLUSION: Although the overall reduction in intravitreal therapy was maintained to year 4, the inferior vision in SRT treated eyes effectively reversed the conclusions of the year 2 primary outcome analysis and no longer supports the use of SRT to treat neovascular AMD. Including standard care, masked, extended follow-up within a clinical trial may provide useful clinical insight.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02243878.},
}

Humans
Female
Double-Blind Method
Visual Acuity
Male
Follow-Up Studies
Treatment Outcome
Aged
*Radiosurgery/methods/adverse effects
*Wet Macular Degeneration/drug therapy/radiotherapy
Angiogenesis Inhibitors/therapeutic use/administration & dosage
Middle Aged
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Aged, 80 and over
*Macular Degeneration

@article {pmid42315822,
year = {2026},
author = {Venkatesh, P},
title = {Tyrosine Kinase Receptors, Inhibition, and Potential Role in the Pharmacotherapy of Retinal Disorders.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42315822},
issn = {2193-8245},
abstract = {Over the past two decades, impressive gains in the restoration and maintenance of visual acuity have been made in patients with, otherwise blinding, chronic retinal diseases such as neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) using intravitreal pharmacotherapy against vascular endothelial growth factor (VEGF). However, there is serious economic burden, continued potential for risks, and potential drug resistance owing to the necessity of repeated injections so as to sustain the initial gains of therapy. Although efforts such as intravitreal treatment with dual pathway inhibitors and sustained drug release implants have been introduced to address such concerns, they do not seem to be the ideal approaches. Consequently researchers continue to explore more plausible solutions, among which tyrosine kinase inhibition seems to have a strong potential to reduce the treatment burden. In this review, the nature of protein kinases and tyrosine kinases, their receptors, and their downstream signaling effects are discussed, followed by the role of receptor tyrosine kinases (RTK) and their inhibitors in the treatment of retinal diseases such as nAMD and DME.},
}

@article {pmid42316110,
year = {2026},
author = {Thakali, S and Shrestha, M and Gauchan, A and Gurung, HB},
title = {Indications and outcome of intravitreal bevacizumab injection in a Community Eye Hospital, Nepal.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42316110},
issn = {1471-2415},
mesh = {Humans ; *Bevacizumab/administration & dosage ; Retrospective Studies ; Male ; Intravitreal Injections ; Female ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Visual Acuity ; Middle Aged ; Treatment Outcome ; Aged ; Nepal ; Tomography, Optical Coherence ; Hospitals, Community ; Adult ; Follow-Up Studies ; *Retinal Diseases/drug therapy/physiopathology/diagnosis ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; },
abstract = {BACKGROUND: This study aimed to evaluate the indications and real-world treatment outcomes of intravitreal bevacizumab in a resource-limited community eye hospital setting.

METHODS: This retrospective study included patients who received IVB injection at Hetauda Community Eye Hospital between January 2019 and December 2022.

INCLUSION CRITERIA: [Formula: see text]1 IVB injection; retinal diagnosis confirmed clinically and by Optical Coherence Tomography (OCT) where available.

EXCLUSION CRITERIA: missing baseline Visual Acuity (VA) or OCT,[Formula: see text] month follow-up. Median visual acuity (VA) and central macular thickness (CMT) changes were compared using Wilcoxon signed‑rank test.

RESULTS: A total of 418 injections were administered to 247 patients (260 eyes). After excluding those lost to follow‑up, 221 patients (234 eyes) were included in the analysis. Median baseline CMT was 366 μm and improved to 236 μm (p < 0.001). Most patients received one injection (57%) followed by two injections (30%). The median baseline VA was 0.78 log MAR and remained 0.78 log MAR overall (p = 0.108), but subgroup improvements were significant in DME, nAMD, BRVO, and central retinal vein occlusion (CRVO).

CONCLUSION: IVB resulted in significant anatomical and functional improvements in patients with retinal diseases. The findings reflect real‑world outcomes in a community‑level eye hospital, where cost barriers limit repeated injections. The limitations of this study include its retrospective design, variable follow‑up, absence of control group, and limited numbers of injections.},
}

Humans
*Bevacizumab/administration & dosage
Retrospective Studies
Male
Intravitreal Injections
Female
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
Visual Acuity
Middle Aged
Treatment Outcome
Aged
Nepal
Tomography, Optical Coherence
Hospitals, Community
Adult
Follow-Up Studies
*Retinal Diseases/drug therapy/physiopathology/diagnosis
Vascular Endothelial Growth Factor A/antagonists & inhibitors

@article {pmid42317156,
year = {2026},
author = {Endo, H and Tanaka, T and Saito, M and Kase, S and Sawada, I and Katsuta, S and Sakaguchi, T and Ishida, S},
title = {Detection of Latent Macular Lesions by Preoperative Optical Coherence Tomography and Associated Factors in Japanese Cataract Patients.},
journal = {Journal of cataract and refractive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.jcrs.0000000000002006},
pmid = {42317156},
issn = {1873-4502},
abstract = {PURPOSE: The purpose of this study was to determine the detection rate and associated factors of latent macular lesions using preoperative Spectral-domain optical coherence tomography (SD-OCT) in Japanese patients scheduled for cataract surgery with no clinically confirmed macular abnormalities.

SETTING: Teine Keijinkai Hospital, Sapporo, Japan.

DESIGN: Retrospective observational study.

METHODS: We included 316 eyes of 316 Japanese cataract patients scheduled for surgery between January 2023 and December 2024 who had no suspected macular pathology on slit-lamp biomicroscopy. All patients underwent comprehensive ophthalmic examinations and SD-OCT, and the detection rate of latent macular lesions and their associated factors were investigated.

RESULTS: Latent macular lesions were detected in 30 eyes (9.5%) of 316 patients with a mean age of 76.8 ± 8.8 years. The most frequent lesions were epiretinal membrane (15 eyes, 4.7%), followed by irregular elevation of the retinal pigment epithelium (10 eyes, 3.2%). Clinically significant lesions requiring immediate surgical modification or additional treatment were identified in 3 eyes (1.0%), including a full-thickness macular hole (1 eye) and neovascular age-related macular degeneration (2 eyes). Age was independently associated with latent macular lesions (odds ratio 1.10, 95% Confidence Interval 1.04-1.16, P<0.01).

CONCLUSION: Preoperative OCT screening may contribute to the evaluation of latent macular lesions, particulary in elderly cohort, and lead to optimized surgical planning.},
}

@article {pmid42307174,
year = {2026},
author = {Su, Y and He, Y and Pu, J and Zhuang, X and Zhang, X and Gan, Y and Wen, F},
title = {Correlation Between RPE Aperture and Photoreceptor Integrity in Non-Neovascular AMD: A Longitudinal Study Using OCT and 3D Morphological Analysis.},
journal = {Translational vision science & technology},
volume = {15},
number = {6},
pages = {21},
doi = {10.1167/tvst.15.6.21},
pmid = {42307174},
issn = {2164-2591},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology/diagnostic imaging ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; *Macular Degeneration/pathology/diagnostic imaging ; Aged ; *Imaging, Three-Dimensional/methods ; Longitudinal Studies ; *Photoreceptor Cells, Vertebrate/pathology ; Retinal Detachment/pathology/diagnostic imaging ; Aged, 80 and over ; Visual Acuity/physiology ; },
abstract = {PURPOSE: The purpose of this study was to investigate longitudinal morphological changes of retinal pigment epithelium (RPE) apertures within pigment epithelial detachment (PED) and their association with photoreceptor integrity in non-neovascular age-related macular degeneration (AMD).

METHODS: This retrospective analysis included 22 eyes from 21 patients with RPE apertures within PED. During a mean follow-up of 11.4 ± 5.8 months, optical coherence tomography (OCT) with 3D volumetric analysis was used to measure RPE aperture diameter/area, PED dimensions, and areas of ellipsoid zone (EZ) loss and outer nuclear layer (ONL) thinning. Correlation and multivariate regression analyses were performed.

RESULTS: RPE apertures significantly enlarged in diameter and area, accompanied by progressive EZ loss and ONL thinning (all P ≤ 0.001). PED height (P = 0.018) and volume (P = 0.031) decreased, whereas PED width increased (P = 0.019). RPE aperture size showed strong cross-sectional and longitudinal correlations with photoreceptor damage (r up to 0.942 and 0.928, respectively, all P < 0.001, remaining significant after false discovery rate [FDR] correction). Multivariate regression demonstrated that change in RPE aperture diameter was independently associated with concurrent changes in EZ loss (β = 1.009, P < 0.001) and ONL thinning (β = 0.679, P = 0.001). Additionally, a larger baseline aperture diameter was an independent factor associated with greater visual acuity decline (P = 0.015).

CONCLUSIONS: RPE apertures enlarge over time and are closely associated with worsening photoreceptor damage, supporting RPE aperture progression as a dynamic biomarker of ongoing photoreceptor degeneration in non-neovascular AMD.

TRANSLATIONAL RELEVANCE: Quantitative OCT-based assessment of RPE aperture expansion enables clinically applicable monitoring of photoreceptor degeneration and visual risk in non-neovascular AMD.},
}

Humans
*Retinal Pigment Epithelium/pathology/diagnostic imaging
*Tomography, Optical Coherence/methods
Retrospective Studies
Female
Male
*Macular Degeneration/pathology/diagnostic imaging
Aged
*Imaging, Three-Dimensional/methods
Longitudinal Studies
*Photoreceptor Cells, Vertebrate/pathology
Retinal Detachment/pathology/diagnostic imaging
Aged, 80 and over
Visual Acuity/physiology

@article {pmid42308567,
year = {2026},
author = {Park, M and Kim, SH},
title = {Age-related macular degeneration and secondary fracture risk in patients with hip fractures.},
journal = {Injury},
volume = {57},
number = {8},
pages = {113450},
doi = {10.1016/j.injury.2026.113450},
pmid = {42308567},
issn = {1879-0267},
abstract = {Research on the relationship between age-related macular degeneration (AMD) and secondary fracture risk following hip fractures is scant. We aimed to examine whether AMD increases the risk of secondary fractures following hip fracture surgery. This retrospective cohort study was conducted using data from the Korean National Health Insurance Service Senior Cohort (2002-2019). Secondary fractures were defined as hip, wrist, humerus, spine, ankle, or pelvic fractures occurring within 6 months after hip fracture surgery. Patients diagnosed with AMD within 6 months postoperatively were identified. Covariates included age, sex, income, insurance type, Charlson Comorbidity Index, residential area, disability status, and hospital size and type. Associations between AMD and secondary fractures were analyzed using Cox proportional hazards models. Among 18 611 patients with hip fractures, 93 were diagnosed with AMD and 26 experienced secondary fractures. Patients with AMD had a significantly higher risk of secondary fractures than those without AMD (adjusted hazard ratio, 1.70; 95% confidence interval, 1.16-2.51). Overall, AMD was associated with an increased risk across all fracture types. Effective management of AMD may help reduce the risk of secondary fractures.},
}

@article {pmid42309064,
year = {2026},
author = {Ma, J and Zhu, L and Duan, P and Ding, T and Cheng, Z and Li, B and Wang, Q and Ma, X and Deng, Y and Lamba, DA and Gao, Y},
title = {Paired pre- and post-transplant human immunoprofiling identifies an IFN-γ-JAK1 axis limiting stem-cell-derived RPE engraftment.},
journal = {Cell stem cell},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.stem.2026.05.006},
pmid = {42309064},
issn = {1875-9777},
abstract = {Neovascular age-related macular degeneration is a major cause of irreversible blindness, and current therapies do not restore photoreceptors or retinal pigment epithelium (RPE). Human embryonic stem-cell-derived RPE (hESC-RPE) transplantation represents a potential regenerative strategy, but immune rejection limits durable engraftment. Here, we combine immune profiling of blood, aqueous humor, and retinal tissue with allogeneic co-cultures and humanized models to define determinants of graft vulnerability and assess a graft-directed intervention. We identify a Th1-skewed, IFN-γ-rich immune milieu across the circulation and eye and show that IFN-γ-JAK1 signaling promotes an immunogenic state in hESC-RPE, marked by increased HLA expression and antigen presentation features. Brief ex vivo conditioning with ruxolitinib attenuates this response while preserving epithelial properties. In humanized retinal degeneration models, conditioned grafts show reduced T/natural killer (NK)-cell infiltration, prolonged survival, and improved visual function without chronic systemic immunosuppression, supporting ex vivo JAK inhibition as a feasible adjunct to RPE cell therapy.},
}

@article {pmid42309346,
year = {2026},
author = {Vogels, DHJ and Ma, Q and Boote, C and Klaver, CCW and LaPointe, VLS and Dickman, MM},
title = {Scleral remodeling in myopia: mechanisms and therapeutic approaches.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101486},
doi = {10.1016/j.preteyeres.2026.101486},
pmid = {42309346},
issn = {1873-1635},
abstract = {High myopia is the leading cause of visual impairment worldwide, driven by excessive axial elongation resulting in biomechanical weakening of the sclera, and increasing the risk of complications such as posterior staphyloma, myopic macular degeneration, retinal detachment, cataract, and glaucoma. Conventional myopia management strategies aim to slow axial elongation in childhood, leaving patients with high myopia at risk of vision-threatening complications as they age. For these individuals, targeted therapies that strengthen the weakened sclera represent a promising, yet still experimental, approach. This review provides an overview of the role of the sclera in myopia progression, emphasizing changes in extracellular matrix composition, collagen organization, biomechanical integrity, and signaling pathways. Investigational scleral therapies are discussed, including posterior scleral reinforcement techniques, crosslinking modalities, pharmacological strategies, and tissue engineering approaches, with discussion of their mechanisms, preclinical and clinical evidence, and translational challenges. Particular attention is given to translational barriers, such as safe delivery to the posterior pole, retinal safety, and the absence of standardized outcome measures that link biomechanical reinforcement to functional benefit. Advances in imaging and in vivo biomechanical assessment, such as polarization-sensitive optical coherence tomography, Brillouin microscopy, and ultrasound-based elastography, hold promise for earlier risk stratification and treatment monitoring. By integrating insights from biomechanics, molecular biology, and therapeutic innovation, this review highlights the sclera as both a key driver of myopia pathology and a promising therapeutic target. Continued interdisciplinary collaboration will be essential to translate these experimental approaches into clinically viable treatments capable of reducing the growing burden of high myopia worldwide.},
}

@article {pmid42310032,
year = {2026},
author = {Budnik, A and Tuchliński, J and Lisowski, Ł and Michnowska-Kobylińska, M and Dmuchowska, DA and Chlabicz, M and Szpakowicz, A and Dubatówka, M and Kondraciuk, M and Kamiński, K and Konopińska, J},
title = {Cardiovascular peptide markers are associated with age-related macular degeneration in the Bialystok PLUS general population cohort.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-55028-4},
pmid = {42310032},
issn = {2045-2322},
support = {2023/ABM/03/000024//Agencja Badań Medycznych/ ; },
abstract = {Age-related macular degeneration (AMD) and cardiovascular disease (CVD) share numerous risk factors; however, protein biomarkers for AMD are lacking. We investigated whether circulating cardiovascular peptide biomarkers are associated with AMD in the population-based Białystok PLUS cohort. This cross-sectional analysis included 699 participants aged ≥ 50 years (AMD + = 93; AMD[-] = 606) examined between 2018 and 2023. AMD was graded from fundus photos with the use of the Wisconsin and modified International Classification systems. Ninety-two cardiovascular proteins were quantified in serum with the Olink Target Cardiovascular III panel. Age-adjusted linear or logistic regressions assessed biomarker-AMD associations, and receiver-operating-characteristic (ROC) curves evaluated discriminative performance. After adjustment, AMD+ participants exhibited lower galectin-4 (β = - 0.15, p = 0.043) and TNF-receptor-superfamily-member-10 C (TNFRSF10C) (β = - 0.17, p = 0.037) concentrations and higher von Willebrand factor (vWF) levels (β = 0.22, p = 0.036) versus AMD[-] individuals. Galectin-4, TNFRSF10C, and vWF predicted AMD with areas under the ROC curve of 0.613 (95% confidence interval [CI] 0.516-0.709), 0.606 (0.520-0.692), and 0.594 (0.500-0.687), respectively. Optimal cut-offs were 4.05 NPX for galectin-4, 5.09 NPX for TNFRSF10C, and 8.03 NPX for vWF, yielding sensitivities/specificities of 57%/63%, 58%/62% and 55%/63%, respectively. Elevated vWF and reduced galectin-4 and TNFRSF10C are independently associated with AMD, suggesting overlapping vascular, inflammatory and apoptotic pathways with CVD. Incorporation of these peptides into risk-stratification algorithms could enhance early AMD detection and motivate mechanistic studies targeting the TRAIL-TNFRSF10C axis and galectin-mediated signaling.},
}

@article {pmid42313414,
year = {2026},
author = {Carrera, WM and Zeng, A and Cheong, KX and Hoang, QV and Jung, JJ and Rofagha, S},
title = {Outcomes in Neovascular Age-Related Macular Degeneration After Copayment Assistance Defunding.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.2093},
pmid = {42313414},
issn = {2168-6173},
}

@article {pmid42300673,
year = {2026},
author = {Sagurski, N and Jaggi, D and Lincke, JB and Wolf, S and Zinkernagel, MS and Dysli, C},
title = {Monitoring of Geographic Atrophy Progression in Age-Related Macular Degeneration Using Fluorescence Lifetime Imaging Ophthalmoscopy.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {6},
pages = {31},
doi = {10.1167/iovs.67.6.31},
pmid = {42300673},
issn = {1552-5783},
mesh = {Humans ; Female ; *Ophthalmoscopy/methods ; *Geographic Atrophy/diagnosis/etiology ; Disease Progression ; Aged ; Male ; Fluorescein Angiography/methods ; Tomography, Optical Coherence/methods ; *Macular Degeneration/complications/diagnosis ; Aged, 80 and over ; Follow-Up Studies ; Fundus Oculi ; Optical Imaging/methods ; Visual Acuity ; },
abstract = {PURPOSE: The purpose of this study was to examine fluorescence lifetime (FLT) changes within the border zone of geographic atrophy (GA) due to age-related macular degeneration (AMD) using fluorescence lifetime imaging ophthalmoscopy (FLIO).

METHODS: Patients with GA due to AMD were included. Fundus autofluorescence (FAF) intensity, spectral-domain optical coherence tomography (OCT), color fundus photography, and FLIO imaging were carried out at baseline and approximately 5 years of follow-up. GA progression was measured based on FAF images. FLT were measured at five different regions of interest: fovea, retina unaffected by GA, GA, and two areas directly next to the border zone of atrophy.

RESULTS: Thirty-two eyes of 17 patients (9 female patients, mean age = 77.4 years) were included. The GA area increased by an average of 1.21 mm2/year. At the GA border, FLT gradually decreased toward the unaffected retina at each visit and gradually increased in all zones over time. The FLT gradient at the border zone correlated significantly with the GA growth rate (P = 0.02, r2 = 0.17).

CONCLUSIONS: Areas of GA showed significantly prolonged FLT compared to unaffected surrounding retinal tissue, confirming previous reports. The border zone FLT gradient was predictive of GA progression rate.},
}

Humans
Female
*Ophthalmoscopy/methods
*Geographic Atrophy/diagnosis/etiology
Disease Progression
Aged
Male
Fluorescein Angiography/methods
Tomography, Optical Coherence/methods
*Macular Degeneration/complications/diagnosis
Aged, 80 and over
Follow-Up Studies
Fundus Oculi
Optical Imaging/methods
Visual Acuity

@article {pmid42300675,
year = {2026},
author = {Martinez, TL and Zacharias, ZR and Lee, K and Han, IC and Jiao, C and Bach, BB and Roos, B and Chava, S and McCormick, MM and Sinkey, C and Wu, AP and Mukhopadhyay, C and Coussa, RG and Russell, J and Binkley, EM and Boldt, HC and Folk, JC and Russell, SR and Mullins, RF and Fingert, JH and Wang, K and Abramoff, MD and Stone, EM and Scheetz, TE and Houtman, JCD and Sonka, M and Sohn, EH},
title = {MMP9 Genotype and Systemic T-Cell Subsets Correlate With Structural and Functional Outcomes in Neovascular Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {6},
pages = {29},
doi = {10.1167/iovs.67.6.29},
pmid = {42300675},
issn = {1552-5783},
mesh = {Humans ; *Matrix Metalloproteinase 9/genetics/metabolism ; Genotype ; Female ; *Polymorphism, Single Nucleotide ; Male ; Flow Cytometry ; Enzyme-Linked Immunosorbent Assay ; *T-Lymphocyte Subsets/immunology ; Tomography, Optical Coherence ; Aged ; Immunophenotyping ; Aged, 80 and over ; *Wet Macular Degeneration/genetics/immunology ; Subretinal Fluid ; *Choroidal Neovascularization/genetics ; },
abstract = {PURPOSE: Genetic studies implicate the matrix metalloproteinase-9 (MMP9) locus in neovascular age-related macular degeneration (nvAMD) risk but genotype-phenotype associations of MMP9 with nvAMD are lacking. This study aimed to investigate the influence of MMP9 genotype and T-cell subset frequency on structural and functional treatment outcomes in nvAMD.

METHODS: We reanalyzed single-cell RNA sequencing data and used ELISA and flow cytometry in THP-1-derived monocytes to measure immune cell expression of MMP9 within human choroids. In a clinical nvAMD cohort of 38 patients, we genotyped the nvAMD risk single nucleotide polymorphism (SNP; rs4810482) and quantified retinal fluid using deep-learning-based optical coherence tomography (OCT) image analysis. On a subset of nine patients, we performed high-dimensional immunophenotyping.

RESULTS: MMP9 is predominantly expressed in mature THP-1-derived dendritic-like cells (ELISA, P = 0.009; flow cytometry, P = 0.001). Patients with the TC genotype of MMP9 exhibited greater disease severity compared to CC or TT genotypes with a significantly higher total retinal fluid volume (P = 0.009). Immunophenotyping revealed that higher proportions of circulating CD8+ effector memory T cells re-expressing CD45RA (TEMRA) were associated with increased residual subretinal fluid (P = 0.03), indicating persistent disease activity.

CONCLUSIONS: MMP9 genotype affects structural and functional outcomes in patients with nvAMD. Along with the observed systemic immune dysregulation, these findings support the role of a MMP9-dendritic-T-cell axis in nvAMD immunopathogenesis and highlight this as a potential therapeutic target.},
}

Humans
*Matrix Metalloproteinase 9/genetics/metabolism
Genotype
Female
*Polymorphism, Single Nucleotide
Male
Flow Cytometry
Enzyme-Linked Immunosorbent Assay
*T-Lymphocyte Subsets/immunology
Tomography, Optical Coherence
Aged
Immunophenotyping
Aged, 80 and over
*Wet Macular Degeneration/genetics/immunology
Subretinal Fluid
*Choroidal Neovascularization/genetics

@article {pmid42303288,
year = {2026},
author = {Zhang, Y and Pu, J and Zhuang, X and Hao, X and Chen, X and He, Y and Zhang, G and Li, M and Ji, Y and Wen, F},
title = {Choroidal vascular hyperpermeability and submacular haemorrhage in polypoidal choroidal vasculopathy: a multi-field ICGA analysis.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2026-329600},
pmid = {42303288},
issn = {1468-2079},
abstract = {PURPOSE: To investigate the association between choroidal vascular hyperpermeability (CVH) and the occurrence of submacular haemorrhage (SMH) in polypoidal choroidal vasculopathy (PCV).

METHODS: This retrospective, cross-sectional study included 189 eyes of 159 patients with treatment-naïve PCV. Eyes were categorised into haemorrhage (n=84) and non-haemorrhage (n=105) groups based on the extent of subretinal or subretinal pigment epithelium haemorrhage. Nine-field indocyanine green angiography (ICGA) was performed to evaluate the presence, number, topographic distribution and area of CVH. Logistic regression and correlation analysis were performed to identify factors associated with SMH.

RESULTS: The cohort comprised predominantly male patients (67.3%), with a mean age of 65.4±7.6 years. The haemorrhage group showed significantly lower CVH prevalence (32.1% vs 68.6%; p<0.001) and median CVH count (0 vs 1; p<0.001) compared with the non-haemorrhage group. Multivariate model demonstrated that both the presence (p<0.001) and higher count (p=0.004) of CVH were independently associated with a reduced likelihood of SMH. Topographically, this negative association was most pronounced for CVH located in the posterior pole, central nasal and central superior quadrants (all p<0.05). A weak but significant inverse correlation was also observed between the total area of CVH and the area of haemorrhage (Spearman's r=-0.248).

CONCLUSIONS: The presence and counts of CVH are inversely associated with the occurrence of SMH in PCV, suggesting CVH may serve as a 'pressure-relief window' to dissipate suddenly elevated choroidal vascular pressure which predisposes to vessel rupture.},
}

@article {pmid42303289,
year = {2026},
author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Iakupova, EM and Milea, D and Bron, AM and Lamirel, C and Nangia, V and Wang, YX and Panda-Jonas, S},
title = {Intereye differences in myopic macular degeneration, intraocular pressure and axial length: the Two-Continent Eye Study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329068},
pmid = {42303289},
issn = {1468-2079},
abstract = {PURPOSE: To assess associations of myopic macular degeneration (MMD) with intraocular pressure (IOP).

METHODS: The project included the population-based Beijing Eye Study (n=3335 participants; age: 40+ years), Ural Eye and Medical Study (n=5589; age: 40+ years), Ural Very Old Study (n=566; age: 85+ years) and Ural Children Eye Study (n=4325; age: 6+ years) and Central India Eye and Medical Study (n=4514; age: 30+ years). MMD was defined according to the Meta-analysis for Pathologic Myopia Study Group.

RESULTS: The study population included 35 778 eyes (18 328 individuals) (age: 46.9±23.1 years; range: 6-100 years) (axial length: 23.2±1.0 mm; range: 18.08-34.20 mm). Longer axial length was associated with higher IOP (ß:0.03; p<0.001) with adjusting for age (ß:0.01; p<0.001), sex (ß:-0.19; p=0.006) and MMD-stage (ß:0.47; p<0.001). Intereye axial length difference correlated (r[2]=0.11) with higher intereye difference in IOP (ß: 0.03; p<0.001) after adjusting for age (ß: 0.06; p<0.001), sex (ß: -0.07; p<0.001) and higher intereye difference in MMD-stage (ß: 0.32; p<0.001). Higher intereye IOP difference correlated (r[2]=0.03) with higher intereye axial length difference (ß: 0.03; p<0.001) after adjusting for age (ß: -0.15; p<0.001), but not with intereye difference in MMD-stage (p=0.90). Higher intereye difference in MMD-stage was associated (r[2]=0.10) only with higher intereye axial length difference (ß: 0.32; p<0.001) and sex (ß: 0.01; p=0.04). Higher intereye difference in MMD prevalence (defined as MMD-stage 3+) correlated with intereye axial length difference (ß: 0.24; p<0.001) and female sex (ß: 0.02; p=0.006) but not with intereye IOP difference (p=0.14).

CONCLUSIONS: Although IOP was associated with longer axial length, MMD stage and MMD prevalence were not significantly related to IOP, neither in an interindividual comparison nor in an intraindividual intereye comparison. The data point against a therapeutic IOP reduction as a measure to reduce development or progression of MMD.},
}

@article {pmid42304501,
year = {2026},
author = {Chen, Y and Liu, C and Chen, J and Huang, Y and Pan, G and Wang, P and Hu, Y and Chen, L and Zhang, Y and Wang, Y},
title = {Single-cell and spatial analyses reveal endothelial-macrophage inflammatory crosstalk in dry age-related macular degeneration.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-026-08393-7},
pmid = {42304501},
issn = {1479-5876},
abstract = {BACKGROUND: Dry age-related macular degeneration (AMD) is characterized by progressive degeneration of the retinal pigment epithelium-choroid interface, accompanied by immune dysregulation. However, the cellular interactions and regulatory mechanisms driving macrophage activation in this process remain incompletely understood.

METHODS: We integrated spatial transcriptomics and single-cell RNA sequencing data from a photo-oxidative damage mouse model and human dry AMD samples. A series of bioinformatic analyses, including cell-cell communication analysis, enrichment analysis, and pseudotime trajectory analysis, were performed to characterize cellular features and regulatory pathways.

RESULTS: In the photo-oxidative damage mouse model, the RPE-choroid region showed marked infiltration of myeloid cells. In human dry AMD samples, SLC16A10-positive macrophages were enriched and exhibited pro-inflammatory features. Further analysis revealed that endothelial cells regulate SLC16A10-positive macrophages through the TNFSF10-TNFRSF10B pathway, with NFKB1 acting as a key regulator to activate NF-κB signaling, thereby promoting the formation of a vascular-immune inflammatory niche.

CONCLUSIONS: This study systematically characterizes immune remodeling in the RPE-choroid region in dry AMD and identifies an endothelial-macrophage TNFSF10-TNFRSF10B-NF-κB signaling pathway that drives disease progression. These findings provide new insights into disease mechanisms and suggest potential therapeutic targets for dry AMD.},
}

@article {pmid42304926,
year = {2026},
author = {Mukherjee, S and Ray, SK and Mukherjee, S},
title = {Linking Neurodegeneration and Age-related Macular Degeneration: Unified Pathways and Intervention Strategies.},
journal = {CNS & neurological disorders drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0118715273450093260523224914},
pmid = {42304926},
issn = {1996-3181},
abstract = {Age-related macular degeneration (AMD) is caused by the degeneration of photoreceptors and retinal pigment epithelium (RPE) along with drusen deposition and is the leading cause of vision loss in older adults. Both these structures within the central nervous system (CNS) utilize common neuro-inflammatory mechanisms because the retina is an outgrowth of the brain. Like the brain, the eye has its own physical characteristics and surface molecules as well as a tendency towards specific immune reactions. Numerous distinct neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Frontotemporal dementia (FTD) that impact the brain present as eye symptoms, and the conventional diagnosis of these neurodegenerative disorders (NDs) is often preceded by ocular symptoms. Furthermore, several eye-specific disorders have characteristics in common with other CNS disorders. NDs and AMD share common key features, such as tau and amyloid-β deposits, oxidative stress response, chronic inflammation, and dysregulation of microglia and müller glia. Common pathological mechanisms include complement activation, amyloid aggregation, neuroinflammation, vascular impairment, and cell death, providing a basis for a convergent neuroimmune axis between retinal and cerebral degeneration. Comparing these age-related diseases will facilitate the identification of shared risk factors, convergent molecular pathways, and potential cross-applicable therapeutic strategies, such as anti-inflammatory, anti-complementary, anti-apoptotic, and anti-VEGF-based approaches. This knowledge may enhance understanding of neurodegenerative diseases, help identify early biomarker development for diagnosis, and enable the design of targeted therapeutic strategies.},
}

@article {pmid42305344,
year = {2026},
author = {Sadikan, MZ and Ahmad Hairi, H and Lambuk, L},
title = {Understanding the link between lipid and ocular disorders for effective therapy.},
journal = {Archives of medical science : AMS},
volume = {22},
number = {2},
pages = {583-601},
pmid = {42305344},
issn = {1734-1922},
abstract = {Cholesterol is an essential lipid for cellular integrity and metabolic homeostasis; however, dysregulated cholesterol metabolism is increasingly recognized as a key contributor to multiple ocular diseases. Beyond its established role in cardiovascular pathology, emerging evidence implicates altered lipoprotein balance, impaired cholesterol transport, and lipid-driven inflammation in the pathogenesis of age-related macular degeneration, retinal vascular diseases, cataracts, and glaucoma. This review integrates current knowledge on cholesterol synthesis, transport, and regulation with ocular-specific mechanisms, emphasizing the differential roles of low-density lipoprotein, high-density lipoprotein, and triglyceride-rich lipoproteins. Key molecular pathways, including the mevalonate-SREBP axis, ABCA1/ABCG1-mediated reverse cholesterol transport, VEGF-driven angiogenesis, oxidative stress signaling, and inflammatory cascades, are critically discussed. Clinical and translational implications are highlighted, particularly the potential ocular benefits of lipid-modulating therapies such as statins, fenofibrate, and antioxidant supplementation. Understanding cholesterol as a modifiable determinant of ocular health may enable integrated preventive strategies and guide future therapeutic innovation in vision-threatening diseases.},
}

@article {pmid42305797,
year = {2026},
author = {Conte, S and Nassisi, M and Mainetti, C and Seregni, L and Viola, F},
title = {Posterior segment inflammation with venous involvement following a switch to a ranibizumab biosimilar (Ximluci®): a case report.},
journal = {American journal of ophthalmology case reports},
volume = {43},
number = {},
pages = {102609},
pmid = {42305797},
issn = {2451-9936},
abstract = {PURPOSE: To describe an unusual case of posterior segment inflammation occurring in temporal association with a switch from reference ranibizumab to its biosimilar, Ximluci®.

OBSERVATIONS: A 77-year-old woman with neovascular age-related macular degeneration presented for an unscheduled visit reporting mild subjective visual loss one day after the second monthly intravitreal injection of ranibizumab biosimilar Ximluci following ten consecutive monthly injections of reference ranibizumab without adverse events. Clinical examination revealed mild optic disc edema, and peripapillary venous leakage on fluorescein angiography, without arteriovenous filling delay or ischemic signs. Multimodal imaging findings were consistent with posterior segment inflammation with venous involvement. Infectious and systemic inflammatory work-up was negative. The patient was treated with systemic and topical corticosteroids, resulting in progressive resolution of inflammatory signs. Due to suboptimal anatomical response of the underlying neovascular lesion and the recent inflammatory episode, therapy was subsequently switched to 2 mg Aflibercept, which was well tolerated without recurrence of intraocular inflammation.

CONCLUSION AND IMPORTANCE: This case highlights a rare episode of posterior segment inflammation occurring in temporal association with a switch to a ranibizumab biosimilar. Although ranibizumab biosimilars have demonstrated a favorable safety profile in clinical trials and regulatory assessments, uncommon inflammatory reactions may emerge in real-world settings. Careful clinical monitoring following treatment switching and continued post-marketing surveillance are essential to further characterize the ocular safety of these agents.},
}

@article {pmid42306086,
year = {2026},
author = {Rezek, FO and Sanchez-Pintado, B and Eden, ER and Corral-Serrano, JC and Aychoua, N and Webster, AR and de Guimarães, TAC and Carr, AF and Michaelides, M and Cheetham, ME and van der Spuy, J},
title = {Antisense oligonucleotide allele-specific targeting of EFEMP1 in a patient-derived model of Doyne honeycomb retinal dystrophy.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {2},
pages = {102955},
pmid = {42306086},
issn = {2162-2531},
abstract = {Doyne honeycomb retinal dystrophy is an incurable juvenile macular dystrophy that leads to visual impairment by early to mid-adulthood. It is an autosomal dominant disorder caused by a c.1033C>T, p.(Arg345Trp) variant in EFEMP1, and is characterized by the early onset of extracellular deposition of drusen between the retinal pigment epithelium and underlying Bruch's membrane. In this study, we developed an antisense oligonucleotide approach to target EFEMP1. We reprogrammed patient-derived renal epithelial cells to induced pluripotent stem cells, followed by directed differentiation to retinal pigment epithelium and compared the phenotype to gene-corrected and EFEMP1 knockout patient-derived retinal pigment epithelium. In the patient-derived disease model, remodeling of the extracellular matrix (ECM) occurred with progressive accumulation of the drusen-associated proteins apolipoprotein E and collagen IV, in addition to the intracellular accumulation and extracellular deposition of lipids. We developed an allele-specific antisense oligonucleotide which specifically and effectively promoted the clearance of the EFEMP1 c.1033C>T transcript in the patient-derived disease model following assisted or gymnotic delivery. Gymnotic delivery rescued remodeling of the ECM, reduced intracellular accumulation of lipids, and cleared extracellular deposits, even after the onset of the disease phenotype, suggesting that this could be a practical and effective therapeutic approach.},
}