@article {pmid42826319,
year = {2026},
author = {Wu, Y and Jiao, Z and Liu, Y and Zhou, Y and Li, H and Chen, X and Liu, G},
title = {Association between oxidative balance score and prevalent age-related macular degeneration in US adults: A cross-sectional NHANES 2005-2008 study.},
journal = {Medicine},
volume = {105},
number = {40},
pages = {e50973},
pmid = {42826319},
issn = {1536-5964},
support = {2021ZQNZD012//Fujian Major Research Grants for Young and Middle-aged Health Professionals/ ; X2022018-SP//Special Project of Fujian University of Traditional Chinese Medicine/ ; },
mesh = {Humans ; *Macular Degeneration/epidemiology/metabolism ; United States/epidemiology ; Cross-Sectional Studies ; Female ; Nutrition Surveys ; Prevalence ; Middle Aged ; Male ; *Oxidative Stress/physiology ; Aged ; Adult ; Life Style ; Risk Factors ; Diet ; },
abstract = {The association between oxidative balance score (OBS) and age-related macular degeneration (AMD) in US adults currently remains unknown. This research aimed to explore the specific association between OBS and AMD. OBS was acquired based on dietary and lifestyle factors, including 16 nutrients and 4 lifestyle components. Weighted logistic regressions were used to explore the associations between OBS and the prevalence of AMD. Subgroup analyses and interaction tests were conducted to understand the relationships across different populations. Furthermore, linear or nonlinear correlations were assessed by spline smoothing and threshold effect analyses. A total of 2408 participants were enrolled from the National Health and Nutrition Examination Surveys (NHANES) in the United States. This research demonstrated a negative association between OBS and AMD; an increase in OBS may reduce the AMD prevalence. Specifically, lifestyle OBS showed the most consistent inverse association with AMD. Higher lifestyle OBS was associated with lower odds of prevalent AMD, while total and dietary OBS showed directionally inverse but non-significant associations after full adjustment. This negative association varied significantly across different subgroups, with more pronounced effects observed in younger or unmarried individuals, non-Hispanic Black races, and those with diabetes or hyperlipidemia within each stratum. Specifically, it was found that this association effect of OBS with AMD was observably greater in people aged 40 to 49 years [OR = 1.05 (0.91, 1.21), P for interaction = 0.0191], unmarried people [OR = 1.38 (0.83, 2.30), P for interaction = 0.0125], non-Hispanic Black [OR = 1.16 (0.90, 1.49), P for interaction = 0.0215], patients with diabetes [OR = 1.25 (1.01, 1.56), P for interaction = 0.0228], and people without hyperlipidemia [OR = 1.67 (1.23, 2.28), P for interaction = 0.0338]. Furthermore, no statistical evidence of nonlinear association was identified using spline smoothing. There exists a possible negative association between OBS and AMD in US adults. OBS is associated with AMD prevalence.},
}

Humans
*Macular Degeneration/epidemiology/metabolism
United States/epidemiology
Cross-Sectional Studies
Female
Nutrition Surveys
Prevalence
Middle Aged
Male
*Oxidative Stress/physiology
Aged
Adult
Life Style
Risk Factors
Diet

@article {pmid42827124,
year = {2026},
author = {Daniele, P and Goodchild, C and Ahmed, E and Bisoukis, A and Salvatore, S},
title = {Three-year real-world outcomes of faricimab in pretreated eyes with treatment-resistant neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42827124},
issn = {1476-5454},
}

@article {pmid42828615,
year = {2026},
author = {Hashiya, N and Maruko, I and Tanaka, K and Honjo, J and Miyara, Y and Watanabe, Y and Maruko, R and Nakai, A and Wakatsuki, Y and Itagaki, K and Maehira, M and Terao, N and Kataoka, K and Okada, AA and Koizumi, H and Mukai, R and Sekiryu, T and Mori, R and Iida, T and , },
title = {Correction: Six-month outcomes with a reduced two-injection induction (2+TAE) regimen of aflibercept 8 mg in treatment-naive neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10384-026-01418-0},
pmid = {42828615},
issn = {1613-2246},
}

@article {pmid42824051,
year = {2026},
author = {Vidal-Oliver, L and Terheyden, J and Behning, C and Basten, V and Kornau, M and Schlößer, L and Luhmann, UFO and Moll, KP and Zakaria, N and Leal, S and Schmid, M and Valckenberg, SS and Holz, F and Finger, RP and Saßmannshausen, M and , },
title = {Cuticular Drusen and the Risk of Progression to Late Age-Related Macular Degeneration: A MACUSTAR Study Report.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101375},
pmid = {42824051},
issn = {2666-9145},
abstract = {PURPOSE: To analyze the prevalence of cuticular drusen (CD) and their relationship with other structural biomarkers in the progression to late age-related macular degeneration (AMD) within the MACUSTAR study (ClinicalTrials.gov Identifier: NCT03349801).

DESIGN: Longitudinal European multicenter cohort study.

SUBJECTS: 585 study participants at a mean age of 72.1 ± 7.0 years with intermediate age-related macular degeneration (iAMD) at baseline visit.

METHODS: Using multimodal imaging, study eyes with iAMD were graded at baseline visit for CD and other AMD-associated biomarkers, including retinal pigment epithelium-drusencomplex (RPEDC) volume, reticular pseudodrusen (RPD), hyper-reflective foci (HRF), and pigmentary abnormalities (PA). We analyzed the prevalence of structural biomarkers according to CD status. Multivariable time-discrete hazard models were used to assess the association of CD alongside RPEDC volume, RPD, HRF, and PA on the progression to late-stage AMD within a 4-year follow-up period.

MAIN OUTCOME MEASURES: Hazard ratio (HR) of progression from intermediate to late-stage AMD.

RESULTS: At baseline, 15.9% of iAMD eyes (93/585 participants; age 71.0 ± 7.2 years) presented with CD, with the following phenotype distribution: type 1, 45.2%; type 2, 32.2%; and type 3, 22.6%. RPD was less prevalent in eyes with CD (11.8%) compared to eyes without (29.9%), whereas other structural biomarkers were comparably prevalent between individuals with and without CD. Progression to late AMD occurred in 6% of eyes with CD (n = 6) and 16.0% without CD (n = 78). CD alone did not significantly modify the risk of AMD progression (HR = 0.49; 95% confidence interval [CI], 0.21‑1.12; P = 0.09). However, coexisting CD and RPD showed the highest risk (HR, 5.9; 95% CI, 1.1-31.5; P < 0.04), exceeding RPD alone (HR, 3.5; 95% CI, 2.3-5.5; P < 0.0001) or RPEDC volume (HR, 1.3; 95% CI, 1.1-1.5; P = 0.01). The presence of HRF and PA on top of CD did not significantly impact the risk of progression beyond the presence of HRF or PA alone. Over time, CD showed coalescence (37.6%), resorption (19.4%), and pigmentary changes (28.0%).

CONCLUSIONS: In iAMD, CD alone does not significantly modify the risk of progression to late AMD in the absence of RPD. However, when CD and RPD coexist, the risk of progression to late AMD is increased. Further investigations, including genetic analyses, are needed to better understand the mechanisms underlying this association.

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

@article {pmid42824271,
year = {2026},
author = {O Kozhevnikova, S and Nikulich, IF and Derbeneva, AS and Devyatkin, VA and Kolosova, NG and Fursova, AZ},
title = {The APOE ε2 allele is associated with risk of neovascular age-related macular degeneration in a Russian cohort.},
journal = {Vavilovskii zhurnal genetiki i selektsii},
volume = {30},
number = {5},
pages = {824-829},
doi = {10.18699/vjgb-26-83},
pmid = {42824271},
issn = {2500-0462},
abstract = {The APOE ε2 allele is associated with risk of neovascular age-related macular degeneration in a Russian cohort.},
}

@article {pmid42824725,
year = {2026},
author = {Larsen, PP and Delyfer, MN and Korobelnik, JF and Delcourt, C and Merle, BMJ},
title = {Plasma Vitamin D and Intermediate Age-Related Macular Degeneration: Insights from the Longitudinal ALIENOR Study.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101364},
pmid = {42824725},
issn = {2666-9145},
abstract = {OBJECTIVE: Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults, with limited options to prevent disease progression. Vitamin D may influence AMD pathogenesis through anti-inflammatory, antioxidative, and antiangiogenic effects. This study aims to investigate the association between deseasonalized plasma 25-hydroxyvitamin D [25(OH)D] levels and the risk of incident AMD, as well as longitudinal changes in macular layer thickness in an elderly population.

DESIGN: Population-based cohort study.

PARTICIPANTS: Seven hundred eyes from 429 participants aged ≥65 years from the ALIENOR Study, followed up over 18 years.

METHODS: Baseline deseasonalized plasma 25(OH)D levels were measured and categorized as sufficient (≥50 nmol/l), insufficient (25-49 nmol/l), or deficient (<25 nmol/l). Cox proportional hazards models adjusted for demographic, lifestyle, and clinical covariates were used to estimate the risk of incident AMD. Longitudinal linear mixed-effects models assessed changes in outer retinal layer thicknesses derived from OCT imaging.

MAIN OUTCOME MEASURES: Incident intermediate and advanced AMD based on fundus color photographs and OCT.

RESULTS: The mean baseline deseasonalized plasma 25(OH)D level was 37.9 ± 14.9 nmol/l. Vitamin D deficiency (<25 nmol/l) was significantly associated with increased risk of incident intermediate AMD compared to sufficient levels (≥50 nmol/l, hazard ratio [HR] = 2.34; 95% confidence interval [CI]: 1.19-4.61; P = 0.01), while insufficiency (25-49 nmol/l) showed a borderline increased risk (HR = 1.74; 95% CI: 0.98-3.08; P = 0.06). No significant associations were observed with advanced AMD. Vitamin D-deficient participants also experienced a significant increase in retinal pigment epithelium-Bruch membrane (RPE-BM) complex thickness over time (β = 0.07 μm/year; 95% CI: 0.01-0.13; P = 0.02), while other outer retinal layers showed no significant change.

CONCLUSIONS: Low deseasonalized plasma 25(OH)D levels were associated with a higher risk of developing intermediate AMD and progressive thickening of the RPE-BM complex, a key retinal structure implicated in AMD pathogenesis. These findings support an association hypothesis and highlight vitamin D status as a candidate modifiable factor worthy of further investigation.

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

@article {pmid42825629,
year = {2026},
author = {Jonas, JB and Jonas, RA and Wang, YX and Panda-Jonas, S},
title = {Association Between Extrafoveal Paravascular Retinoschisis and Central Retinal Vessel Trunk Dragging in High Myopia.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {12},
pages = {7},
doi = {10.1167/iovs.67.12.7},
pmid = {42825629},
issn = {1552-5783},
mesh = {Humans ; Tomography, Optical Coherence/methods ; *Retinoschisis/epidemiology/etiology/physiopathology/diagnosis ; *Retinal Vessels/pathology/physiopathology ; Female ; Male ; Prevalence ; Aged ; Middle Aged ; Aged, 80 and over ; *Myopia, Degenerative/complications/physiopathology ; Optic Disk/pathology ; Fovea Centralis ; Cross-Sectional Studies ; Visual Acuity ; },
abstract = {PURPOSE: To assess occurrence and associations of myopic extrafoveal paravascular retinoschisis (EPR).

METHODS: Using optical coherence tomographic images of the optic disc and macula, taken in the population-based Beijing Eye Study, we assessed prevalence and associations of parapapillary retinoschisis.

RESULTS: The study included 3336 individuals (3336 eyes) with a mean age of 64.2 ± 9.6 years (range, 50-93) and a mean axial length of 23.4 ± 1.2 mm (range, 20.16-30.88). EPR prevalence (34/3336, 1.0%; 95% confidence interval [CI], 0.6-1.4) increased from 1/3046 (0.03%) to 8/173 (4.6%; 95% CI, 1-8), 4/74 (5.4%; 95% CI, 0-11), 10/25 (40%; 95% CI, 19-61), and 11/18 (61%; 95% CI, 36-86) with axial lengths of ≤25.0 mm, 25.01 to 26.0 mm, 26.01 to 27.0 mm, 27.01 to 28.0 mm, and >28.0 mm, respectively. Higher EPR prevalence was associated (multivariable analysis) with higher prevalence of central retinal vessel trunk dragging (CRVTD) (odds ratio [OR] = 8.81; 95% CI, 3.02-25.7; P < 0.001) and longer axial length (OR = 2.97; 95% CI, 2.27-3.89; P < 0.001; Nagelkerke R2 = 0.55), or alternatively with longer fovea-optic disc center distance (OR = 2.79; 95% CI, 1.55-5.03; P < 0.001). In a nonlinear manner, EPR prevalence increased steeply beyond an axial length of 25.5 mm and a fovea-disc center distance of 5.5 mm. These relationships were complemented by univariate associations between EPR prevalence and temporal retinal vessel straightening, smaller angle kappa, higher myopic macular degeneration stage and prevalence, and larger parapapillary beta zone and gamma zone.

CONCLUSIONS: EPR was a common feature in eyes with severe/high axial myopia and was mainly associated with CRVTD and longer axial length or fovea-disc center distance. As a hypothesis, EPR, contrary to myopic foveoschisis, may be due to a stretching of the temporal large retinal vessels in highly myopic eyes, related to the fovea-disc distance elongation.},
}

Humans
Tomography, Optical Coherence/methods
*Retinoschisis/epidemiology/etiology/physiopathology/diagnosis
*Retinal Vessels/pathology/physiopathology
Female
Male
Prevalence
Aged
Middle Aged
Aged, 80 and over
*Myopia, Degenerative/complications/physiopathology
Optic Disk/pathology
Fovea Centralis
Cross-Sectional Studies
Visual Acuity

@article {pmid42822746,
year = {2026},
author = {Simmerly, CM and Islam, MA and Williamson, AP and Corbin, EA},
title = {Spatio-temporal Mechanosensitive Phagocytic Response of Retinal Pigment Epithelial Cells to Reversible Changes in Substrate Stiffness.},
journal = {Acta biomaterialia},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.actbio.2026.09.053},
pmid = {42822746},
issn = {1878-7568},
abstract = {In aging and diseased retina, Bruch's membrane (BrM) stiffens heterogeneously, impairing phagocytic clearance of photoreceptor outer segments by the overlying retinal pigment epithelial (RPE) monolayer and contributing to retinal degeneration. While substrate stiffness is known to influence RPE phagocytosis, conventional assays lack the spatial resolution to capture how mechanical cues coordinate behavior across the monolayer over time. Here, dynamic magnetorheological elastomer (MRE) substrates are combined with an automated machine-learning image-analysis pipeline to simultaneously quantify particle engagement kinetics, cell morphology, and spatial organization at single-cell resolution. This combination enables spatiotemporal observation of RPE mechanosensitivity inaccessible to population-level assays. Substrate stiffness shaped particle engagement kinetics, modulating engagement rate and maximum particle capacity. Soft substrates additionally increased cell area and eccentricity, suggesting stiffness-dependent cytoskeletal remodeling. Strikingly, cells with increased levels of particle engagement form spatially localized clusters whose organization was sensitive to substrate stiffness, revealing that mechanical cues coordinate engagement behavior at the tissue level rather than acting on cells independently. This work reveals how dynamic BrM stiffening drives coupled changes in particle engagement kinetics, cell morphology, and spatial coordination, highlighting the tissue-level complexity of RPE mechanosensitivity. Together, these findings reframe RPE particle engagement as a spatially coordinated, mechanosensitive process, providing new insight into how dynamic alterations in extracellular mechanical environments regulate cellular function. STATEMENT OF SIGNIFICANCE: The retinal pigment epithelium (RPE) clears cellular debris daily to maintain vision, a process that falters as the underlying tissue stiffens with age, a hallmark of macular degeneration. Existing tools capture only population averages on static surfaces, obscuring both the timing and spatial organization of the response. This study combines dynamically tunable substrates with automated machine-learning image analysis to quantify receptor-mediated particle engagement at single-cell resolution across time and space. Mechanical transitions, not stiffness magnitude alone, accelerate engagement rate while reducing total capacity. Cell shape predicts particle engagement activity in a stiffness-dependent manner, and highly active cells cluster spatially in patterns governed by the mechanical environment. These findings reframe RPE dysfunction as a spatially coordinated, mechanosensitive process with direct implications for early AMD.},
}

@article {pmid42818647,
year = {2026},
author = {Jensen, RD and Mullin, NK and Mulfaul, K and Miller, JEB and Navratil, E and Voigt, AP and Scheetz, T and Wiley, LA and Stone, E and Tucker, B and Mullins, R},
title = {Transcriptomic Characterization of Terminal Complement Complex-bound Cells in Human Choroid Using Single-Cell RNA Sequencing.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.09.05.749603},
pmid = {42818647},
issn = {2692-8205},
abstract = {Age-related macular degeneration (AMD) is among the leading causes of blindness worldwide. Early AMD is characterized by dysfunction in the choroid, including early dropout of endothelial cells and increased deposition of the complement cascade's membrane attack complex (MAC) in the choriocapillaris. In this study, we used a single-cell RNA sequencing-based approach with barcoded antibodies to measure abundance of the MAC and other surface proteins at single cell resolution on RPE/choroid samples from four aged human donor eyes. We included antibodies to detect the MAC, CD34, CD45, and complement regulators CD55 and CD59, in addition to control antibodies. Our analysis of these data revealed cell clusters with expected gene expression profiles and antibody-based detection of CD34 and CD45 congruent with transcriptome-based cell identity. We also detected surface complement regulators CD55 and CD59 across a wide variety of cell types. Across endothelial cells, surface CD55 and CD59 appeared more abundant on venous clusters, and abundance of each was correlated with expression of a third complement regulator, clusterin (CLU). The MAC was detected on a variety of cell types, but was most abundant on the surface of cells in the macrophage family, smooth muscle cells, and pericytes. We confirmed these findings by identifying MAC deposition on choriocapillaris pericytes using immunohistochemistry for MAC, endothelial, and pericyte markers. Ultimately, these data showcase a valuable new approach to analyze gene expression and surface complement in human donor eyes, and provide novel insight into patterns of MAC deposition and complement protection in the aging human choroid.},
}

@article {pmid42819474,
year = {2026},
author = {Zhao, X and Cheng, T and Zhang, W and Gu, X and Zhao, Q and Chen, Y and Meng, L and Zhang, J and Qiu, B and Li, L and Cheng, S and Wang, Z and Wang, C and Wang, Y and Yang, Z and Shi, Z and Guo, Y and Liu, S and Chen, Y},
title = {Dissecting the angiogenic mechanism of pachychoroid polypoidal choroidal vasculopathy.},
journal = {iMeta},
volume = {},
number = {},
pages = {e70176},
pmid = {42819474},
issn = {2770-596X},
abstract = {Polypoidal choroidal vasculopathy (PCV) is a distinct variant of neovascular age-related macular degeneration (AMD) and a major cause of vision loss in older adults, yet its pathogenesis remains poorly understood. Pachychoroid PCV is a subtype characterized by poor treatment response, minimal typical AMD features, and dilated choroidal vessels. Using a multicenter PCV cohort, we conducted plasma multi-omics analyses and identified enrichment of fluid shear stress and atherosclerosis (FSS-AS) signaling pathways in this subtype. The pachychoroid phenotype, together with FSS-AS enrichment, implicated altered choroidal hemodynamics in its pathogenesis. By inducing choroidal circulatory hypertension (CCH) in mice, we recapitulated, for the first time, the hallmark ocular lesions of pachychoroid PCV. Single-cell sequencing identified the cellular origin of these angiogenic lesions and implicated endothelin-1 (EDN1) as a key effector. Alleviating choroidal hypertension, reducing EDN1 expression, or pharmacologically blocking the endothelin receptor A (EDNRA, the receptor for EDN1), prevented lesion formation. In vitro, disturbed fluid shear stress upregulated EDN1 in choroidal endothelial cells and promoted pathological remodeling and angiogenesis through EDNRA. Collectively, our findings define a pathogenic cascade wherein CCH induces abnormal hemodynamics (disrupted fluid shear stress) and drives angiogenesis via the EDN1/EDNRA axis, offering mechanistic insight and identifying a potential therapeutic target for pachychoroid PCV.},
}

@article {pmid42815670,
year = {2026},
author = {Schulz, A and Al-Nawaiseh, S and Wakili, P and Krötz, C and Germann, A and Farese, G and Burri, C and von Briesen, H and Claaßen, C and Schmidt, S and Weber, A and Southan, A and Borchers, K and Szurman, P and Stanzel, BV},
title = {Subretinal integration of a vascular endothelial growth factor slow-release gelatin functionalized cell carrier for retinal pigment epithelium cell therapy.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {154685},
doi = {10.1016/j.ijbiomac.2026.154685},
pmid = {42815670},
issn = {1879-0003},
abstract = {PURPOSE: Replacement of retinal pigment epithelium (RPE) with a cell-based therapeutic represents a potential treatment strategy for age-related macular degeneration (AMD). To improve subretinal integration via angiogenesis, RPE cell carrier transplants were equipped with gelatin for vascular endothelial growth factor (VEGF) release after implantation.

METHODS: Gelatin coatings were applied to the basal side of polyethylene terephthalate (PET) membranes using doctor blading, dip coating, or pipetting to optimize film thickness and reproducibility. Human fetal RPE (hfRPE) cells were cultured on treated PET and monitored for morphology, pigmentation, transepithelial resistance, polarization, and expression of RPE-relevant proteins by immunofluorescence. PET/gelatin loaded w/or w/o VEGF, or PET/gelatin/VEGF carriers with hfRPE were subretinally implanted for 6 weeks into pigmented rabbits onto RPE wounds. Subretinal integration was assessed using optical coherence tomography (OCT), fluorescein angiography (FA), indocyanine green angiography (ICGA), and histological and immunofluorescence staining.

RESULTS: Reproducible gelatin films were formed by pipetting a defined volume of solution, depending on concentration and gelatin type. In vitro, gelatin coating promoted hfRPE cell growth, monolayer formation, pigmentation, and tight junction development. Polarized secretion of VEGF and pigment epithelium-derived factor (PEDF) was maintained and bestrophin, ezrin and RPE65 showed a qualitatively more homogeneous distribution in gelatin treated hfRPE cells compared to controls. Six weeks after implantation, the hfRPE layer appeared largely intact as judged by a double layered OCT hyperreflectivity, and vascular channel-like structures were observed in the subimplant space.

CONCLUSIONS: Integration of RPE grafts into the subretinal space is promoted by PET carriers coated with VEGF-loaded gelatin.},
}

@article {pmid42815674,
year = {2026},
author = {Li, D and Hu, S and Wu, M},
title = {Comment on "Cost-Effectiveness of Photobiomodulation for Intermediate Dry Age-Related Macular Degeneration: A Model-Based Analysis Using the LIGHTSITE III 24-Month Trial".},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.051},
pmid = {42815674},
issn = {1879-1891},
}

@article {pmid42815678,
year = {2026},
author = {Tian, M and Bu, W and Cheng, X and Shen, Z and Fei, Y and Jiang, L and Sun, M and Wang, Z and Xiao, J and Cheng, D and Zhao, X},
title = {Integrating epidemiology and mechanistic studies links PFAS exposure to ocular diseases and implicates PFOS-associated glaucoma risk through the PI3K/Akt-MMP3 axis.},
journal = {Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association},
volume = {218},
number = {},
pages = {116416},
doi = {10.1016/j.fct.2026.116416},
pmid = {42815678},
issn = {1873-6351},
abstract = {Perfluoroalkyl substances (PFAS) pose health risks, but their association with glaucoma, cataracts, and age-related macular degeneration remains uncertain. First, a cross-sectional analysis of NHANES (2005-2008) was performed using multiple logistic regression and mixture models, including weighted quantile sum (WQS), quantile g-computation (QGC), and Bayesian kernel machine regression (BKMR), to examine single and mixed PFAS exposures in relation to ocular diseases. Second, Mendelian randomization was applied to further explore the PFOS-glaucoma association. Third, network toxicology and in vitro experiments were employed to generate mechanistic hypotheses. Cross-sectional results suggested positive associations between PFOS and glaucoma, and between PFNA and cataracts. Sex-stratified analyses revealed positive associations of PFOS with glaucoma in females, and in males, of PFDA with glaucoma and PFNA with cataracts. Mixture models suggested that PFOS may be a driving factor for glaucoma risk. Sensitivity analyses yielded results generally consistent with the primary findings. Mendelian randomization supported a positive PFOS-glaucoma association. Network toxicology and in vitro experiments indicated that PFOS activates PI3K/Akt signaling and reduces MMP3 expression. LY294002 treatment partly restored MMP3 expression, supporting a role for PI3K/Akt signaling in this response. These results suggest that the PI3K/Akt-MMP3 axis may be involved in PFOS-induced extracellular matrix changes in trabecular meshwork cells.},
}

@article {pmid42818173,
year = {2026},
author = {Pandey, NB and Mirando, AC and Almeida, DRP and Dang, S and Lally, DR and Bridges, WZ and Campochiaro, PA and Popel, AS and Green, JJ},
title = {A Single Suprachoroidal Injection of AXT107 (Gersizangitide), a Multimodal, Long-Acting Integrin-Disrupting Peptide, in Patients with Neovascular Age-Related Macular Degeneration: Results of the Phase 1/2a DISCOVER Trial.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.09.19.26363031},
pmid = {42818173},
abstract = {PURPOSE: To evaluate the safety, tolerability, and preliminary bioactivity of a single suprachoroidal injection of AXT107 (Gersizangitide), a multimodal integrin-disrupting peptide that acts on both the VEGFA pathway and angiopoietin-Tie2 pathway, in eyes with neovascular age-related macular degeneration (nAMD).

DESIGN: Phase 1/2a, open-label, dose-escalation clinical trial.

PARTICIPANTS: Fifteen subjects with active nAMD, including 11 treatment-experienced partial responders to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and 4 treatment-naïve subjects; 14 eyes met the protocol-specified baseline imaging criterion and were included in efficacy analyses.

METHODS: Study eyes received a single suprachoroidal injection of AXT107 microparticles at doses of 0.125, 0.25, or 0.5 mg and were followed for 40 weeks. Protocol-specified rescue intravitreal anti-VEGF treatment was permitted from week 12 based on protocol-specified best-corrected visual acuity (BCVA) or central subfield thickness (CST) criteria; anti-VEGF treatment before Week 12 was investigator-initiated. Primary outcomes were ocular and systemic safety through week 40; secondary outcomes included change in CST, change in BCVA, and time to first protocol-specified rescue injection.

MAIN OUTCOME MEASURES: Incidence of ocular and systemic adverse events, intraocular pressure (IOP), CST, BCVA, and time to first protocol-specified rescue injection.

RESULTS: Twenty subjects were screened and 15 enrolled across 4 U.S. sites; 3 eyes received 0.125 mg, 3 received 0.25 mg, and 9 received 0.5 mg of AXT107. No serious adverse events related to AXT107 occurred, and no cases of endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or clinically significant intraocular inflammation were observed through week 40. No clinically meaningful intraocular pressure (IOP) elevations occurred at any dose, and no subject required chronic IOP-lowering therapy. Among the 14 eligible eyes included in efficacy analyses, 2 treatment-experienced eyes, Eyes 08 and 09, completed 40 weeks without protocol-specified anti-VEGF rescue, and 1 treatment-experienced eye, Eye 10, first received protocol-specified rescue at Week 36. At the last on-treatment visit, BCVA changes ranged from +15 to -31 ETDRS letters; 3 eyes gained ≥5 letters, 3 gained ≥10 letters, and 1 gained ≥15 letters. Among the 14 eligible eyes, anatomical improvements in CST were observed in at least 1 eye in each dose cohort. The most durable responses were seen in treatment-experienced eyes receiving 0.5 mg (median durability of 36 weeks), whereas treatment-naïve 0.5-mg eyes showed more variable courses and generally earlier protocol-specified rescue in this small cohort.

CONCLUSIONS: In this first-in-human study, a single suprachoroidal injection of AXT107 up to 0.5 mg was well tolerated through Week 40, with no drug-related serious adverse events, no clinically significant intraocular inflammation, and no sustained IOP elevations. After a single suprachoroidal AXT107 injection, 2 eyes completed 40 weeks without protocol-specified rescue anti-VEGF treatment, and 1 additional eye received its first protocol-specified rescue treatment at Week 36. The exploratory observation that durability appeared greatest in treatment-experienced eyes supports further controlled study of AXT107, particularly in treatment-experienced nAMD populations.},
}

@article {pmid42818498,
year = {2026},
author = {Cui, B and Bex, P},
title = {Central Vision Loss Alters Internal Emotion Representations: Evidence from a Generative Genetic Algorithm Paradigm.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.23.683781},
pmid = {42818498},
issn = {2692-8205},
abstract = {Central vision loss (CVL) from age-related macular degeneration (AMD) profoundly impacts daily life. While much research focuses on visual discrimination and reading, understanding how CVL affects emotional perception remains unexplored. We adapted the genetic-algorithm face paradigm introduced by Carlisi et al. (2021) and extended by Binetti et al. (2022), combining it with a three-dimensional morphable face model, to investigate how healthy young, healthy older, and CVL-affected individuals internally represent facial emotions. Participants evolved faces they perceived to best express 13 distinct emotions (or 4 for the older healthy group). Using a three-cohort design, we separated age effects from CVL-specific effects. Results revealed four significant group differences: Awe Convergence (H = 10.97, p = 0.001), Shame Intensity (H = 10.04, p = 0.005), Interest Range (H = 6.35, p = 0.016), and Interest Stability (H = 4.86, p = 0.026). Additionally, cosine similarity analysis in 199-dimensional face space showed cohorts use fundamentally different facial feature configurations (mean cosine ≈0.006 for YNG vs CVL), suggesting CVL may reorganize emotion representations rather than simply scaling them. These preliminary findings raise questions about whether all emotions require uniform amplification in CVL and point toward the potential value of selective rehabilitation over broad caricaturing approaches.},
}

@article {pmid42810674,
year = {2026},
author = {Berni, A and Rosenfeld, PJ and Bacherini, D and Chakravarthy, U and Chaudary, V and Reibaldi, M and Shen, M and Ting, DSW and Trivizki, O and Viggiano, P and Zur, D and Sadda, S and Borrelli, E},
title = {From Intermediate AMD to Geographic Atrophy: Biomarkers, Endpoints, and a Roadmap for Next-Generation Clinical Trials.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101532},
doi = {10.1016/j.preteyeres.2026.101532},
pmid = {42810674},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible legal blindness worldwide. Treatments exist for late-stage AMD, but none exists for the intermediate stage (iAMD), which precedes significant vision loss. A therapy tested in iAMD would aim to prevent or slow progression to late-stage disease, meaning geographic atrophy or exudative neovascular AMD. The difficulty is that iAMD can persist for five years or longer before it progresses, whereas a trial must reach an answer within approximately two years. Such a trial therefore has to do two things at once: enroll the eyes most likely to progress within that window, and measure an endpoint that moves when progression slows. This review identifies the enrichment and endpoint criteria that make this possible. An enrichment biomarker must predict progression, be reproducibly measured, and be deployable across sites within two years. Optical coherence tomography (OCT) is the best instrument for this purpose because it is well tolerated, quantitative, and already available wherever iAMD trials are run. A single OCT acquisition can measure drusen area and volume, photoreceptor band integrity, hyperreflective foci, calcified drusen, and reticular pseudodrusen. For the endpoint, the onset and growth of large hypertransmission defects and the progressive loss of the outer retinal bands provide continuous structural measures that can be paired with microperimetry to capture function. Drawing on natural history data to model progression and statistical power, we propose a configurable trial design in which OCT both enriches for high-risk eyes and supplies the endpoint.},
}

@article {pmid42810675,
year = {2026},
author = {Jin, K and Zhao, K and Agrawal, R and Ying, GS and Grzybowski, A},
title = {Artificial intelligence for clinical decision-making in retinal disorders: From screening and diagnosis to treatment and longitudinal management.},
journal = {Progress in retinal and eye research},
volume = {115},
number = {},
pages = {101533},
doi = {10.1016/j.preteyeres.2026.101533},
pmid = {42810675},
issn = {1873-1635},
abstract = {Artificial intelligence (AI) in retinal imaging has expanded from image classification to multimodal interpretation, longitudinal prediction, and clinically oriented decision support. This narrative review focuses on four complementary clinical settings: diabetic retinopathy (DR) screening and referral, diabetic macular edema (DME) treatment assessment, neovascular age-related macular degeneration (nAMD) retreatment and longitudinal monitoring, and inherited retinal disease (IRD) diagnosis, genotype-phenotype support, progression modeling, and trial enrichment. We organize the evidence around disease-specific decision points, relevant data modalities, and the requirements for multimodal and longitudinal integration. Evidence is strongest for DR screening, supported by prospective and real-world validation, whereas treatment-oriented applications in DME and nAMD and multimodal diagnostic or prognostic applications in IRDs remain less consistently validated. We highlight the gap between model performance and clinical utility and propose a cautious translational roadmap emphasizing external validation, calibration, uncertainty handling, workflow integration, prospective evaluation, and accountable deployment.},
}

@article {pmid42812627,
year = {2026},
author = {Achuck, K and Soares, R and Solish, D and Popovic, M and Felfeli, T and Muni, R and Shah, C and Baskin, D and Hsu, J and Garg, S},
title = {Effect of Topical Bromfenac 0.09% on Pain Following Intravitreal Antivascular Endothelial Growth Factor Injections.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261464998},
pmid = {42812627},
issn = {2474-1272},
abstract = {PURPOSE: To evaluate the effect of topical bromfenac 0.09% on pain following intravitreal (IVT) injection of antivascular endothelial growth factor (anti-VEGF) medications in patients diagnosed as having choroidal neovascularization secondary to age-related macular degeneration or other etiologies, diabetic macular edema, diabetic retinopathy, or macular edema associated with retinal vein occlusion.

METHODS: A total of 78 adult patients scheduled to receive bilateral anti-VEGF IVT injections were randomized to receive topical bromfenac 0.09% in 1 eye and artificial tears in the fellow eye (control) immediately before the anti-VEGF treatment at 2 academic institutions from March 2021 to June 2022. Pain was evaluated using the Wong-Baker FACES Pain Rating Scale (score range, 0-10) and the Short-Form McGill Pain Questionnaire (score range, 0-5) at baseline (preinjection) and 5 minutes, 6 hours, and 24 hours following injection. Wilcoxon signed-rank sum test was used for statistical comparisons.

RESULTS: In total, 156 eyes were analyzed. Mean baseline pain scores were similar between the bromfenac 0.09% and control groups. Five minutes after injection, eyes randomized to receive bromfenac 0.09% had significantly less pain compared with control eyes receiving artificial tears, on both the Wong-Baker FACES scale (mean raw score, 2.29 vs 2.79; P = .0275) and the McGill Pain Questionnaire (mean raw score, 1.13 vs 2.36; P = .0135). No significant difference in pain scores was noted at 6 hours or 24 hours post-IVT injection.

CONCLUSIONS: Bromfenac 0.09% solution administered to the study eye before IVT anti-VEGF injection reduced pain 5 minutes after injection in comparison with artificial tears. There was no difference in pain between the 2 groups at 6 hours or 24 hours post-IVT injection.},
}

@article {pmid42814127,
year = {2026},
author = {Scrivens, B and Daniele, P and Papazacharia, A and Donia, A and Bailey, C and Maghsoudlou, P and Salvatore, S},
title = {Eighteen-month real-world outcomes of intravitreal aflibercept 8 mg in treatment-naïve neovascular age-related macular degeneration: a UK single-centre experience.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42814127},
issn = {1435-702X},
abstract = {PURPOSE: Intravitreal aflibercept 8 mg was developed to extend treatment intervals and reduce injection burden in neovascular age-related macular degeneration (nAMD). We evaluated visual, anatomical, and durability outcomes over 18 months in routine clinical practice.

METHODS: This retrospective observational study included 102 eyes of 95 treatment-naïve nAMD patients commencing aflibercept 8 mg at a UK tertiary centre. All eyes received three loading injections followed by a treat-and-extend protocol. Best-recorded visual acuity (BRVA), central subfield thickness (CST), intraretinal fluid (IRF), subretinal fluid (SRF), and macular haemorrhage were assessed at baseline, post-loading, 12 months, and 18 months. Linear and generalised mixed-effects models were applied.

RESULTS: Mean patient age was 81.1 ± 6.5 years; 68.4% were female. Mean BRVA was 62.5 ± 12.4 letters at baseline, 67.5 ± 13.7 post-loading, 66.8 ± 15.3 at 12 months (n = 102), and 65.5 ± 18.5 letters at 18 months (n = 73). Mean CST was 317.1 ± 95.4 μm at baseline, 237.9 ± 45.2 μm post-loading, 236.3 ± 51.7 μm at 12 months, and 220.6 ± 32.2 μm at 18 months (n = 73). At 12 months, 51.9% of eyes achieved treatment intervals of ≥ 12 weeks, increasing to 73.9% at 18 months. No cases of endophthalmitis were recorded.

CONCLUSION: Aflibercept 8 mg achieved sustained visual acuity, significant anatomical improvement, and progressively extended treatment intervals over 18 months in treatment-naïve nAMD within routine clinical practice, supporting its effectiveness in reducing treatment burden without compromising disease control.},
}

@article {pmid42814727,
year = {2026},
author = {Ghadimi, M and Begum, H and Zeraatkar, D and Ma, J and Sivaprasad, S and Borrelli, E and Kaiser, P and Steel, DH and Wong, TY and Guymer, R and Wykoff, CC and Chaudhary, V},
title = {OphthoEvidence Report: Comparative effects of treatments for geographic atrophy secondary to age-related macular degeneration: A protocol for a living systematic review and network meta-analysis.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0358699},
pmid = {42814727},
issn = {1932-6203},
mesh = {Humans ; *Geographic Atrophy/therapy/etiology ; *Macular Degeneration/complications ; Network Meta-Analysis as Topic ; Quality of Life ; Systematic Reviews as Topic ; Visual Acuity ; },
abstract = {BACKGROUND: Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), leads to legal blindness in approximately 16% of affected individuals within 6 years. Numerous trials have evaluated interventions to slow GA progression, and many studies are ongoing. However, the comparative benefits and harms of treatments within this rapidly evolving therapeutic landscape have not yet been systematically synthesized.

OBJECTIVES: To present a protocol for a living systematic review and network meta-analysis (NMA) addressing the effects of available interventions for the management of GA.

METHODS: We systematically searched Medline, EMBASE, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov from inception for randomized controlled trials comparing any pharmacologic or non-pharmacologic treatment versus another, placebo, sham, or standard care in adults with unilateral or bilateral GA secondary to AMD. Paired reviewers will independently screen studies, extract data, and assess risk of bias. Outcomes of interest include best-corrected visual acuity (BCVA), untransformed and square root-transformed total GA lesion area, vision-related quality of life, low luminance BCVA, reading speed, mean macular sensitivity, adverse events leading to discontinuation, macular neovascularization, need for rescue treatment, ischemic optic neuropathy, serious ocular adverse events, and serious non-ocular adverse events. For each outcome, if feasible, we will conduct frequentist random-effects NMAs. We will assess the certainty of evidence and interpret findings using the GRADE approach. To maintain this review as a living systematic review, we will conduct updates every six months.

DISCUSSION: This review will provide a comprehensive, trustworthy, and up-to-date summary of evidence on treatments for GA secondary to AMD.

REGISTRATION: Open Science Framework (https://doi.org/10.17605/OSF.IO/W4JHR).},
}

Humans
*Geographic Atrophy/therapy/etiology
*Macular Degeneration/complications
Network Meta-Analysis as Topic
Quality of Life
Systematic Reviews as Topic
Visual Acuity

@article {pmid42806246,
year = {2026},
author = {Cruz, MJ and Limaye, S and Christopher, M},
title = {Current Trends in AI and Eye Disease Diagnostics.},
journal = {Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {},
number = {},
pages = {},
pmid = {42806246},
issn = {1475-1313},
support = {OT2OD032644/OD/NIH HHS/United States ; OT2OD032644/OD/NIH HHS/United States ; OT2OD032644/OD/NIH HHS/United States ; },
abstract = {PURPOSE: Artificial intelligence (AI) has rapidly advanced as an approach for ophthalmic disease detection, driven by the widespread use of high-dimensional imaging modalities (e.g., optical coherence tomography). This review summarises the machine learning and AI approaches for disease detection in ophthalmology and discusses emerging paradigms and highlights key challenges impacting clinical translation.

RECENT FINDINGS: AI-based systems have demonstrated suitably high diagnostic performance across major ophthalmic diseases, including diabetic retinopathy (DR), diabetic macular oedema, glaucoma, age-related macular degeneration and retinopathy of prematurity. Several tools have even received regulatory approval for commercial DR screening. More recently, foundation models trained using self-supervised learning have enabled more generalisable and data-efficient disease detection across datasets and imaging modalities. In parallel, multimodal large language model systems are emerging that integrate imaging and clinical data to support more comprehensive diagnostic workflows. Early agentic AI systems extend this paradigm further by coordinating multiple models to perform disease detection, provide clinical decision support and generate reports. AI-based disease detection in ophthalmology has achieved substantial technical progress but only limited translation into routine clinical practice. Key barriers include technical, clinical, ethical, economic and regulatory concerns. Future efforts should prioritise prospective evaluation in real-world settings, addressing model transparency and bias and alignment with clinical and regulatory requirements. With continued advances, AI has the potential to expand access to care, improve diagnostic accuracy and reduce the global burden of vision loss.},
}

@article {pmid42807675,
year = {2026},
author = {Rák, T and Jin, Y and Chen, M and Csutak, A},
title = {The therapeutic potential of medicinal mushrooms in ophthalmology: from ethnomycology to evidence-based applications.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1887133},
pmid = {42807675},
issn = {1663-9812},
abstract = {Medicinal mushrooms have long been used in traditional medical systems, yet their ophthalmic relevance has only recently been explored. This narrative review provides, to our knowledge, an integrative mapping of medicinal mushroom-derived bioactive compounds in ophthalmology, with particular emphasis on their level of evidence across different ocular diseases. A structured search of PubMed, Scopus, Google Scholar and ScienceDirect (2001-2026) was conducted to identify experimental, clinical, and mechanistic studies addressing antioxidant, anti-inflammatory, immunomodulatory, neuroprotective and antifibrotic pathways in ocular tissues. The findings reveal a marked heterogeneity in evidence levels. A limited subset of fungal-derived compounds - primarily antimicrobial and immunomodulatory agents such as β-lactam antibiotics, cyclosporine A, and mycophenolate mofetil - are supported by high-level clinical evidence (Level 1), while emerging evidence (Level 2) is available for compounds such as Isaria cicadae in dry eye disease and Ganoderma lucidum in age-related macular degeneration. In contrast, the majority of medicinal mushrooms - including Pleurotus spp., Hericium erinaceus, Wolfiporia extensa, and Polyporus umbellatus - remain supported mainly by preclinical studies and traditional use (Level 5 evidence). Experimental data indicate that mushroom-derived polysaccharides and triterpenoids can modulate oxidative stress, inflammation, intraocular pressure, fibrosis, and neuronal survival. Additional compounds demonstrate potential in glaucoma, cataract, and retinal disorders through multitarget mechanisms. Overall, medicinal mushrooms represent a promising but still under-validated therapeutic resource in ophthalmology. The observed disparity between traditional use, experimental evidence, and clinical validation highlights a significant translational gap, underscoring the need for standardized formulations and well-designed clinical trials to enable evidence-based integration into ophthalmic practice.},
}

@article {pmid42808622,
year = {2026},
author = {Eymard, P},
title = {[Anti-VEGF treatment in age related macular degeneration].},
journal = {La Revue du praticien},
volume = {76},
number = {7},
pages = {703-706},
pmid = {42808622},
issn = {2101-017X},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Angiogenesis Inhibitors/therapeutic use ; Intravitreal Injections ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bevacizumab/therapeutic use ; Ranibizumab ; },
abstract = {Intravitreal anti-VEGF (Vascular Endothelial Growth Factor) injections have transformed the prognosis of exudative age-related macular degeneration (AMD) over the past two decades. They are effective in stabilizing the disease, despite the cost of regular injections and follow-up examinations. The advent of biosimilars and second-generation molecules (which allow for longer average treatment intervals) would help to reduce the cost of these therapies. While these treatments have significantly reduced visual impairment due to wet-AMD, they continue to represent a major economic challenge.},
}

Humans
*Macular Degeneration/drug therapy
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Angiogenesis Inhibitors/therapeutic use
Intravitreal Injections
Antibodies, Monoclonal, Humanized/therapeutic use
Bevacizumab/therapeutic use
Ranibizumab

@article {pmid42809677,
year = {2026},
author = {Guzel, A and Devebacak, A},
title = {Bilateral Vortex Keratopathy in a Patient Receiving Long-Term Ribociclib Therapy.},
journal = {Eye & contact lens},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICL.0000000000001312},
pmid = {42809677},
issn = {1542-233X},
abstract = {We report a case of bilateral vortex keratopathy associated with long-term ribociclib therapy in a 67-year-old woman with metastatic breast cancer. The corneal deposits were identified during routine ophthalmic examination after 4 years of continuous treatment. Slit-lamp biomicroscopy revealed bilateral whorl-like epithelial deposits with a subtle morphological appearance compared with classic amiodarone-associated cornea verticillata. The patient had no history of tamoxifen, amiodarone, or chloroquine use, and there were no clinical features suggestive of Fabry disease. The combined severity of the bilateral cortical cataracts and macular changes associated with dry age-related macular degeneration was considered sufficient to explain the reduced visual acuity, whereas the subtle corneal deposits were not considered visually significant. The patient remained asymptomatic, and systemic therapy was continued without modification. This case suggests that ribociclib-associated vortex keratopathy may be detected after prolonged exposure and remain clinically silent at presentation, highlighting the importance of careful clinical assessment to avoid unnecessary interruption of essential oncologic treatment.},
}

@article {pmid42810526,
year = {2026},
author = {Xue, CC and Li, H and Wang, S and Fan, Q and Yu, M and Chee, ML and Li-Gao, R and Willems van Dijk, K and Khor, CC and Tan, ACS and Wong, TY and Cheng, CY},
title = {Cholesteryl Ester Transfer Protein Inhibition and Risk of Age-Related Macular Degeneration.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.09.027},
pmid = {42810526},
issn = {1549-4713},
abstract = {PURPOSE: Cholesteryl ester transfer protein (CETP) inhibitors have shown cardiovascular benefits, but genetically proxied CETP inhibition may increase age-related macular degeneration (AMD) risk. We evaluated this association in European- and East Asian-ancestry populations.

DESIGN: Drug-target Mendelian randomization (MR) and observational genetic association analyses in the UK Biobank and the Singapore Epidemiology of Eye Diseases (SEED) study.

PARTICIPANTS: 457,242 UK Biobank participants without AMD at baseline and 7,058 SEED participants.

METHODS: In drug-target MR, CETP inhibition was instrumented using a CETP protein quantitative trait locus (pQTL) instrument in Europeans and a high-density lipoprotein (HDL)-weighted CETP-region instrument in East Asians. Outcomes included advanced and early AMD in Europeans and exudative AMD, typical neovascular AMD (nAMD), and polypoidal choroidal vasculopathy (PCV) in East Asians. In observational analyses, a CETP pQTL score was evaluated against incident AMD in the UK Biobank, and an HDL-weighted CETP genetic score against prevalent AMD in SEED.

MAIN OUTCOME MEASURES: Risk of AMD RESULTS: In drug-target MR, greater genetically proxied CETP inhibition was associated with higher risks of advanced AMD (OR, 1.45; 95% CI, 1.25, 1.67) and early AMD (OR, 1.29; 95% CI, 1.19, 1.41) in Europeans, and exudative AMD (OR, 3.14; 95% CI, 2.16, 4.57), typical nAMD (OR, 2.84; 95% CI, 1.69, 4.79), and PCV (OR, 3.18; 95% CI, 2.05, 4.93) in East Asians (all P<0.001). In UK Biobank, each 1-SD decrease in the CETP pQTL score, representing greater genetically proxied CETP inhibition, was associated with higher incident AMD risk (HR,1.03; 95% CI, 1.01, 1.06; P=0.008). In SEED, the HDL-weighted CETP genetic score showed a U-shaped association with prevalent early AMD. Compared with the midrange group, higher odds were observed in the highest decile, representing greater genetically proxied CETP inhibition (OR, 1.74; 95% CI, 1.07, 2.72; P=0.019), and the lowest tertile, representing weaker inhibition (OR, 1.50; 95% CI, 1.13, 1.99; P=0.005).

CONCLUSIONS: Greater genetically proxied CETP inhibition was associated with higher AMD risk across genetic analyses in European- and East Asian-ancestry populations. These findings raise a potential retinal safety signal requiring validation in clinical trials and longitudinal observational studies in clinical practice.},
}

@article {pmid42810652,
year = {2026},
author = {Perina, ML and Calcagno, D and Sbardella, D and Deodato, D and Distefano, A and Tuccitto, N and Oliveri, V and Schlotter, F and Faller, P and Grasso, G},
title = {The chemical oxidation of albumin affects its capability to bind amyloid beta 1-40 peptide and to inhibit its aggregation.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {154678},
doi = {10.1016/j.ijbiomac.2026.154678},
pmid = {42810652},
issn = {1879-0003},
abstract = {Human Serum Albumin (HSA) is the most abundant protein in the human body, exerting vital antioxidant and carrier functions. Beyond its systemic roles, HSA is clinically employed as a therapeutic tear supplement to restore the ocular surface proteome in severe dry eye and corneal diseases. However, the functional integrity of HSA is frequently compromised by oxidative stress, a hallmark of several neurodegenerative proteinopathies. While elevated levels of oxidised HSA have been documented in the blood and cerebrospinal fluid of Alzheimer's Disease patients, similar oxidative modifications are implicated in the pathogenesis of glaucoma and Age-related Macular Degeneration, where amyloid-beta (Aβ) peptides deposition and impaired protein clearance drive disease progression. Despite these clinical correlations, the specific impact of oxidative damage on the ability of HSA to chaperone and interact with Aβ peptides remains poorly understood. In this work, we applied several different experimental techniques to study the effect of oxidation on HSA conformation and oligomeric state when Chloramine T (CT) and hydrogen peroxide in Metal Catalysed Oxidation (MCO) are employed. ThT aggregation studies confirmed that the two different oxidised forms of HSA affect Aβ1-40 fibrillation differently. In addition, SPR interaction studies between the two differently oxidised forms of HSA and Aβ1-40 allowed us to prove that CT and MCO induce two different oxidative damages on HSA, which in turn induce lower binding capability towards Aβ1-40. Our results indicate a possible explanation for the role of oxidised HSA in the development and progression of brain and retinal neurodegeneration characterized by accumulation of Aβ.},
}

@article {pmid42798467,
year = {2026},
author = {Vijayan, M and Veerapu, G and J S, N},
title = {A two-stage deep learning framework with progressive feature fusion and attention mechanisms for multi-class retinal disease classification.},
journal = {Frontiers in artificial intelligence},
volume = {9},
number = {},
pages = {1925302},
pmid = {42798467},
issn = {2624-8212},
abstract = {Accurate and efficient automated analysis of Optical Coherence Tomography (OCT) images is critical for large-scale retinal disease screening. However, current deep learning models often fail to simultaneously achieve high classification accuracy, practical computational feasibility, and interpretability. To deal with these problems, this paper presents a deep learning framework on YOLOv11 for eight-class retinal disease classification optimized using a two-stage optimization strategy. The proposed architecture incorporates a Progressive Spatial Fusion (PSF) module to hierarchically integrate multi-scale feature representations, followed by a Squeeze-and-Excitation (SE)-based dual-attention refinement mechanism that refines disease-discriminative features prior to classification. Evaluated on the OCT-C8 dataset, the proposed model achieves 98.00% accuracy, precision, recall, and F1-score, together with 99.70% specificity, while achieving perfect classification performance for the Age-related Macular Degeneration (AMD), Central Serous Retinopathy (CSR), Diabetic Retinopathy (DR), and Macular Hole (MH) classes. Grad-CAM visualizations provide qualitative insights into image regions influencing model predictions and show correspondence with disease-associated structural patterns reported in OCT literature. These results show that the proposed framework provides a good trade-off between classification performance, computational requirements and interpretability and shows potential for automated OCT-based retinal disease screening support.},
}

@article {pmid42799897,
year = {2026},
author = {Yadav, A and Phogat, J and Yadav, M and Bhardwaj, A and Panghal, V and Goel, S and Verma, M and Sharma, S and Singh, M and Kumar, R and Tanwar, M},
title = {A case-control study on IL-8 gene polymorphisms and serum IL-8 levels in patients with age-related macular degeneration in India.},
journal = {Human genetics},
volume = {145},
number = {1},
pages = {},
pmid = {42799897},
issn = {1432-1203},
support = {09 /382(0244)/20 19- EM R-I//Council for scientific and industrial research, New Delhi, India/ ; },
mesh = {Humans ; *Interleukin-8/genetics/blood ; Male ; Case-Control Studies ; Female ; India ; *Polymorphism, Single Nucleotide ; Aged ; *Macular Degeneration/genetics/blood ; Middle Aged ; Genetic Predisposition to Disease ; Genotype ; Gene Frequency ; Alleles ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, with inflammatory and genetic factors contributing to its development. This study examined the association of IL-8 polymorphisms (rs4073, rs2227306, rs2227543) and serum IL-8 levels in a North Indian AMD cohort. A case-control study involving 160 AMD patients and 100 controls was performed. AMD was confirmed through detailed clinical evaluation and diagnostic imaging. Genomic DNA was extracted and genotyped using PCR followed by Sanger sequencing, and serum IL-8 concentrations were determined by ELISA. Statistical analyses were conducted using SPSS v22.0 and SNPstats. AMD patients exhibited significantly higher serum IL-8 levels than control (p < 0.001). ANCOVA adjusting for age and smoking confirmed elevated IL-8 in AMD (adjusted mean: 63.52 pg/ml vs. 41.23 pg/ml in controls; p < 0.001), with higher levels in wet AMD than dry AMD (67.75 pg/ml vs. 54.32 pg/ml; p = 0.043). The IL-8 rs4073 AA genotype and A allele were more frequent in AMD patients (p = 0.006 and p = 0.011, respectively). Multivariate logistic regression showed strong associations between rs4073 AA genotype and AMD risk under codominant (adjusted OR = 2.68; 95% CI: 1.17-6.15; p = 0.025), recessive (adjusted OR = 2.68; 95% CI: 1.27-5.67; p = 0.0067), and log-additive (adjusted OR = 1.50; 95% CI: 1.02-2.20; p = 0.036) models. No significant associations were observed for rs2227306 or rs2227543. Among all participants, AA carriers had significantly higher serum IL-8 levels than TT and AT genotypes (p = 0.018 and p < 0.001). The IL-8 rs4073 AA genotype and elevated serum IL-8 levels may serve as potential markers for AMD susceptibility in the North Indian population.},
}

Humans
*Interleukin-8/genetics/blood
Male
Case-Control Studies
Female
India
*Polymorphism, Single Nucleotide
Aged
*Macular Degeneration/genetics/blood
Middle Aged
Genetic Predisposition to Disease
Genotype
Gene Frequency
Alleles

@article {pmid42800655,
year = {2026},
author = {Wei, Y and Morobeid, H and Daynes, K and Lee, S and Ansari, G and Bredehorst, J and Mireles, J and Nelson, R and Eakins, RT and Brown, T and Pfau, M and Zhang, Y and Schmitz-Valckenberg, S and Fleckenstein, M},
title = {Structure-function associations in eyes with Early Atrophic Age-related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.09.029},
pmid = {42800655},
issn = {1879-1891},
support = {R01 EY034965/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: To characterize baseline structure-function relationships in eyes with early atrophic age-related macular degeneration (AMD) and to identify functional outcomes that best reflect structural disease burden.

DESIGN: Cross-sectional study PARTICIPANTS: A total of 87 eyes from 87 participants enrolled in the ongoing prospective observational study of early atrophic AMD (ClinicalTrials.gov NCT05959005), with incomplete or complete retinal pigment epithelium and outer retinal atrophy and total atrophic lesion size ≤ 1.27 mm² METHODS: Structural metrics derived from multimodal imaging included fundus autofluorescence (FAF)-defined geographic atrophy (GA) lesion size (total and targeted), targeted hypertransmission size, and distance to the fovea (DTF) from the lesion border. Structure-function relationships were evaluated using correlations and univariable linear regressions with multiple-comparison adjustment.

MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), Moorfields Acuity Test (MAT), reading acuity and reading speed, and mesopic and dark-adapted (DA) cyan fundus-controlled perimetry (FCP) using fixed and lesion-targeted macular patterns.

RESULTS: Lesion size-based structural metrics showed the strongest associations with FCP outcomes. In eyes with FAF-defined GA (n = 38), each doubling of targeted GA lesion size was associated with a 3.55 dB decrease in mean targeted mesopic sensitivity and 3.65 dB in mean targeted DA sensitivity (all P < 0.001). Similarly, doubling of targeted hypertransmission size (n = 81) was associated with decreases of 1.65 dB and 1.97 dB in mean targeted mesopic and DA sensitivities, respectively (both P < 0.001; correlations up to ρ = -0.66). In contrast, central visual and reading outcomes were primarily associated with lesion topography. Greater DTF was associated with better BCVA, LLVA, and MAT (approximately 4 to 5 letters per mm) and improved reading acuity (-0.11 logRAD per mm; all adjusted P < 0.05), whereas lesion size-based metrics showed no consistent significant association with these outcomes.

CONCLUSIONS: In early atrophic AMD, lesion size and hypertransmission extent are closely linked to localized FCP sensitivity loss, whereas central visual acuity and reading outcomes are determined by lesion proximity to the fovea. This domain-specific separation supports targeted FCP as a sensitive endpoint for detecting structure-related functional change in early atrophic AMD.},
}

@article {pmid42800947,
year = {2026},
author = {Mallepally, A and Lam, M and Mittal, E and Mahmoudzadeh, R and Salabati, M and Randolph, J},
title = {Comparative Analysis of Systemic Complications of Antivascular Endothelial Growth Factor Therapies in Retinal Diseases.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261484033},
pmid = {42800947},
issn = {2474-1272},
abstract = {Purpose: To compare the systemic safety profiles of antivascular endothelial growth factor (anti-VEGF) agents using a large real-world dataset. Methods: The TriNetX Research Network database was used to identify adults with macular edema secondary to diabetes, retinal vein occlusion, or age-related macular degeneration who received bevacizumab, ranibizumab, or aflibercept (2012-2022) or faricimab (2022-2024). The bevacizumab cohort was matched with the other cohorts using propensity score matching to account for demographic characteristics and comorbidities. Outcomes included stroke, venous thromboembolism, myocardial infarction, hypertension, brain hemorrhage, and renal function. Results: In the propensity score-matched cohorts comparing outcomes between bevacizumab and aflibercept (each n = 9538), bevacizumab was associated with higher mean blood urea nitrogen level (28.07 mg/dL vs 26.89 mg/dL; P = .017), higher mean serum creatinine level (1.86 mg/dL vs 1.72 mg/dL; P = .004), and lower mean estimated glomerular filtration rate (55.64 mL/min vs 58.01 mL/min; P = .003) at 1 to 6 months' follow-up. Compared with the faricimab cohort, the bevacizumab cohort (each n = 3500) showed increased risk of stroke (risk ratio [RR], 1.71, 95% CI, 1.19-2.48), venous thromboembolism (RR, 1.80, 95% CI, 1.11-2.93), myocardial infarction (RR, 1.72, 95% CI, 1.19-2.49), and hypertension (RR, 1.47, 95% CI, 1.19-1.83) within 2 years of follow-up. No significant differences were found between the bevacizumab and ranibizumab cohorts (each n = 2211). Conclusions: Bevacizumab may confer an increased risk of cardiovascular events and differences in renal function parameters compared with aflibercept and faricimab, but not ranibizumab. This underscores the importance of tailoring anti-VEGF therapy to patient-specific profiles, particularly in patients with underlying cardiovascular and renal comorbidities. Further studies in lower-comorbidity populations are needed to clarify these associations.},
}

@article {pmid42803434,
year = {2026},
author = {Remolí-Sargues, L and Monferrer-Adsuara, C and Castro-Navarro, V and López-Salvador, B and Francés-Muñoz, E and López-Sánchez, E and Montero-Hernández, J},
title = {Comparison of Choroidal Vascularity Index Between Type 1 and Type 2 Macular Neovascularization Before and After Anti-VEGF Therapy.},
journal = {Seminars in ophthalmology},
volume = {},
number = {},
pages = {1-8},
doi = {10.1080/08820538.2026.2740663},
pmid = {42803434},
issn = {1744-5205},
abstract = {PURPOSE: To compare choroidal structural features and visual and anatomical outcomes between type 1 and type 2 macular neovascularization (MNV) at baseline and following anti-vascular endothelial growth factor (anti-VEGF) therapy.

METHODS: This retrospective study included 56 eyes of 44 patients with treatment-naïve neovascular age-related macular degeneration treated with intravitreal anti-VEGF. Choroidal vascularity index (CVI), best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (CST), and macular fluid status were assessed at baseline and the final follow-up visit.

RESULTS: At baseline, CMT was significantly lower in type 1 than in type 2 MNV (p 0.047), whereas CVI did not differ significantly between groups (p 0.091). At the final visit, CVI also showed no significant difference between subtypes. BCVA improved and CMT decreased descriptively in both groups, whereas CST decreased and CVI remained essentially stable. After adjustment for baseline values and actual follow-up duration, no significant differences were found between subtypes in final BCVA, CMT, CST, CVI, or macular fluid status (all p > .05).

CONCLUSION: No significant differences in CVI were found between type 1 and type 2 MNV at baseline or final follow-up, and longitudinal changes were comparable between subtypes. These findings do not support a predominant role of choroidal vascularity in distinguishing MNV subtypes. As retinal pigment epithelium integrity was not assessed, its potential contribution remains unclear. Larger prospective studies with standardized treatment protocols are needed to clarify the mechanisms underlying different MNV growth patterns.},
}

@article {pmid42804165,
year = {2026},
author = {Arsoudi, V and Chontos, T and Voutsas, S and Petrou, P and Tyrlis, K and Karavidas, I and Kandarakis, SA and Chondrou, S and Diamanti, S and Angelidis, CD and Georgalas, I},
title = {Lipoprotein and apolipoprotein levels in age-related macular degeneration: A meta-analysis.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261492347},
doi = {10.1177/11206721261492347},
pmid = {42804165},
issn = {1724-6016},
abstract = {PurposeDrusen, the hallmark of AMD, are lipoprotein-rich particles. However, the role of systemic lipid metabolism in their formation remains controversial. This meta-analysis explored the association between ApoA1, ApoA2, ApoB and Lp(a) serum levels and AMD.MethodsWe systematically searched MEDLINE, Cochrane Library, EMBASE and Scopus for relevant studies. WMD meta-analyses were performed for ApoA1 and ApoB, whereas SMD meta-analyses were conducted for ApoA2 and Lp(a) serum levels in AMD patients vs healthy controls.ResultsA total of 11 studies with 5,084 subjects for ApoA1, 4,179 for ApoB, 3,177 for ApoA2 and 3,228 for Lp(a) were included. No significant differences were observed between AMD patients (all subtypes) and controls for serum ApoA1 (WMD = 0.29 mg/dL, -3.75 to 4.32, p = 0.89), ApoB (WMD = -2.16 mg/dL, -5.67 to 1.34, p = 0.23), or Lp(a) (g: -0.14, -0.54 to 0.27, p = 0.50). ApoA2 was significantly different (g = 0.2, 0.07 to 0.34, p = 0.003). In severe AMD (geographic atrophy, neovascular AMD), meta-analysis revealed no significant difference for ApoA1 (WMD = -2.68 mg/dL, -8.87 to 3.52, p = 0.4) or ApoB (WMD = -0.42 mg/dL, -6.20 to 5.32, p = 0.89).ConclusionThis meta-analysis discovered no meaningful association between systemic levels of ApoA1, ApoB, or Lp(a) and the presence or severity of AMD. Despite a significant change in ApoA2, utilizing a Reference Change Value based interpretation, we conclude that observed differences in analyzed markers represent physiological and analytical noise rather than true biological change. Our findings suggest that systemic ApoA1, ApoB, and Lp(a) levels are not elevated in individuals with AMD, though the potential role of ApoA2 warrants further investigation.},
}

@article {pmid42804496,
year = {2026},
author = {Ouyang, Q and Zhou, H and Ji, C and Jiang, H and Zhao, L and Pan, Y and Xiang, S and Hu, X},
title = {Dioscin attenuates D‑galactose‑induced retinal pigment epithelium senescence and epithelial-mesenchymal transition via the TGF‑β2/PI3K/Akt/β‑catenin pathway.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0359423},
pmid = {42804496},
issn = {1932-6203},
mesh = {Animals ; *Diosgenin/analogs & derivatives/pharmacology ; *Epithelial-Mesenchymal Transition/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology ; beta Catenin/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; *Galactose/pharmacology ; *Transforming Growth Factor beta2/metabolism ; Humans ; Mice ; *Signal Transduction/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; *Cellular Senescence/drug effects ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Macular Degeneration/metabolism/drug therapy/pathology ; Cell Line ; Saponins ; },
abstract = {PURPOSE: This study aimed to evaluate the protective effects of Dioscin in an age-related macular degeneration (AMD) -like model and to explore its potential therapeutic mechanisms.

METHODS: The therapeutic potential of Dioscin for AMD was investigated using D-galactose-induced senescence models in ARPE-19 cells (an in vitro preliminary screening model) and C57BL/6J mice using RT-qPCR, western blotting, immunofluorescence, and SA-β-gal staining. Bioinformatic analysis and molecular docking identified TGF-β2 as a computationally predicted potential target of Dioscin in AMD. Key mechanisms involving TGF-β2 and the PI3K/Akt/β-catenin signaling pathway were assessed in vitro using RT-qPCR, western blotting.

RESULTS: In D-galactose-induced senescence models, Dioscin significantly alleviated RPE senescence and EMT. Single-cell transcriptome analysis revealed that TGF-β2 is highly expressed in choroidal vascular endothelial cells of AMD patients. Mechanistically, computational predictions (molecular docking and dynamics simulations) identified TGF-β2 as a computationally predicted potential target of Dioscin, and experimental data showed that Dioscin suppressed D-galactose-induced activation of the TGF-β2/PI3K/Akt/β-catenin pathway in RPE cells, suggesting a potential paracrine regulatory mechanism.

CONCLUSION: Dioscin alleviates RPE senescence and EMT through suppression of the TGF-β2/PI3K/Akt/β-catenin pathway. Single-cell transcriptomics reveals that TGF-β2 is specifically upregulated in choroidal vascular endothelial cells in AMD, suggesting a paracrine mechanism linking vascular pathology to RPE dysfunction. These findings suggest that Dioscin may have potential value in mitigating RPE senescence and EMT in an AMD‑like model, although further validation in more clinically relevant AMD models is required.},
}

Animals
*Diosgenin/analogs & derivatives/pharmacology
*Epithelial-Mesenchymal Transition/drug effects
*Retinal Pigment Epithelium/drug effects/metabolism/pathology
beta Catenin/metabolism
Phosphatidylinositol 3-Kinases/metabolism
*Galactose/pharmacology
*Transforming Growth Factor beta2/metabolism
Humans
Mice
*Signal Transduction/drug effects
Proto-Oncogene Proteins c-akt/metabolism
*Cellular Senescence/drug effects
Molecular Docking Simulation
Mice, Inbred C57BL
Macular Degeneration/metabolism/drug therapy/pathology
Cell Line
Saponins

@article {pmid42805085,
year = {2026},
author = {Castro-Fernández, DC and Cañizo-Outeiriño, A and Martínez, AL and Cuartero-Martinez, A and Rodríguez-Martínez, L and González-Barcia, M and Fernández-Rodríguez, MI and Rodríguez-Cid, MJ and Abraldes, MJ and Almuiña-Varela, P and Mera-Yáñez, MP and de Domingo, B and Gil-Martínez, M and Méndez-Cepeda, MDP and Pazos-González, B and Goméz-Ulla, F and Loza, MI and Ortea, I and Brea, J and Mateos, J and Fernández-Ferreiro, A},
title = {The oxidative and carbonyl stress axis in anti-vascular endothelial growth factor-refractory neovascular age-related macular degeneration: Implications for therapeutic repurposing.},
journal = {European journal of medicinal chemistry},
volume = {320},
number = {},
pages = {119361},
doi = {10.1016/j.ejmech.2026.119361},
pmid = {42805085},
issn = {1768-3254},
abstract = {BACKGROUND AND PURPOSE: Neovascular age-related macular degeneration is a leading cause of irreversible blindness, and approximately 25% of patients respond inadequately to intravitreal anti-VEGF therapy, representing a major unmet clinical need. We aimed to identify repurposable therapeutic alternatives by anchoring a phenotypic screen in the molecular signature of inadequate responders.

EXPERIMENTAL APPROACH: The molecular phenotype of the disease was characterised by data-independent acquisition proteomic profiling of peripheral blood mononuclear cells from patients with an inadequate anti-VEGF response and from controls. Guided by this signature, the Prestwick Chemical Library (1160 approved compounds) was screened in ARPE-19 retinal pigment epithelial cells exposed to cigarette smoke extract. Cytoprotection was assessed by a primary viability assay and examined further by orthogonal high-content imaging of intracellular reactive oxygen species and by concentration-range evaluation.

KEY RESULTS: Baseline profiling showed increased thiol-reductase, lipid-peroxidation, platelet and immune-redox pathways, together with reduced high-density-lipoprotein-associated antioxidant components. Dual angiopoietin-2/VEGF inhibition partially reversed these changes, with oxidative and carbonyl stress emerging as a prominent axis. The single-replicate primary screen performed robustly and recovered 29 primary hits, including established antioxidants, which attenuated intracellular reactive oxygen species in the orthogonal assay. Of six candidates advanced to concentration-range evaluation, todralazine produced the most consistent and pronounced protective effect.

CONCLUSION AND IMPLICATIONS: These preliminary findings nominate todralazine, a hydrazinophthalazine structurally related to known carbonyl-scavenging agents, as a repurposable candidate requiring mechanistic and translational validation, and illustrate the value of anchoring phenotypic screens in disease-relevant molecular signatures.},
}

@article {pmid42794533,
year = {2026},
author = {Wen, L and Li, F and Liu, Y and Zhang, K and Mao, A and Liu, L and Lv, X and Geng, L and Yu, F and Feng, L and Kan, H},
title = {Integrative Proteogenomics and Single-Cell Transcriptomics Prioritize Candidate Causal Proteins and Therapeutic Targets in Age-Related Macular Degeneration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {18},
pages = {},
pmid = {42794533},
issn = {1422-0067},
support = {82500499//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Macular Degeneration/genetics/metabolism ; Animals ; Genome-Wide Association Study ; Mice ; Quantitative Trait Loci ; *Proteogenomics/methods ; Single-Cell Analysis/methods ; *Transcriptome ; Single-Cell Gene Expression Analysis ; Retinal Pigment Epithelium/metabolism ; Polymorphism, Single Nucleotide ; Gene Expression Profiling ; },
abstract = {Age-related macular degeneration (AMD) is a major cause of irreversible visual impairment, yet identifying effector proteins and tissue-specific mechanisms underlying genome-wide association study (GWAS) loci remains challenging. This study aimed to systematically prioritize candidate causal circulating proteins and delineate their cellular and transcriptional dynamics in AMD. We integrated plasma protein quantitative trait loci (pQTL) summary statistics from the UK Biobank Pharma Proteomics Project (UKB-PPP; N=53,022) with FinnGen AMD GWAS data using proteome-wide association studies (PWAS), summary-data-based Mendelian randomization (SMR) with the HEIDI test, and Bayesian colocalization analysis. Prioritized candidates were mapped across human and murine retinal single-cell/single-nucleus RNA sequencing atlases. Transcriptional responsiveness was validated in an independent clinical microarray dataset (GSE103060) and in human retinal pigment epithelial cells (ARPE-19) via in vitro inflammatory stimulation and RT-qPCR. Target tractability was assessed using pharmacological databases. Multi-stage genetic screening prioritized five candidate proteins stratified into two confidence tiers: three Tier 1 causal drivers supported by colocalization (PP4 > 0.80)-including risk factors CSF2, IL20RB, and WARS1 (also known as WARS)-alongside two Tier 2 candidates supported by SMR and HEIDI, comprising risk factor PILRA and inversely associated metabolic factor ACADSB. Retinal transcriptomic mapping localized PILRA specifically to microglia, ACADSB to inner retinal neurons, and WARS1 to photoreceptors, RPE, and vascular compartments, while IL20RB and CSF2 exhibited low baseline expression. In independent validation cohorts, IL20RB and WARS1 were significantly up-regulated in choroidal neovascularization (CNV) membrane-derived RPE from patients with AMD (p<0.01). Exposure of ARPE-19 cells to TNF-α markedly induced mRNA levels of IL20RB (P=0.0025) and WARS1 (p<0.0001). Dual normalization against ACTB as a secondary internal reference yielded consistent significant induction. Pathway enrichment highlighted cytokine-driven receptor cascades (JAK-STAT signaling) and mitochondrial substrate catabolism (branched-chain amino acid and fatty acid metabolism). Drug-target profiling identified small molecules and nutraceuticals interacting with ACADSB, CSF2, and WARS1. By combining large-scale plasma proteomic genetics with single-cell mapping and experimental validation, this study identifies a prioritized set of candidate causal proteins linking neuroimmune activation, vascular remodeling, and mitochondrial bioenergetics in AMD, providing candidate entry points for mechanistic and therapeutic exploration.},
}

Humans
*Macular Degeneration/genetics/metabolism
Animals
Genome-Wide Association Study
Mice
Quantitative Trait Loci
*Proteogenomics/methods
Single-Cell Analysis/methods
*Transcriptome
Single-Cell Gene Expression Analysis
Retinal Pigment Epithelium/metabolism
Polymorphism, Single Nucleotide
Gene Expression Profiling

@article {pmid42794693,
year = {2026},
author = {Angel, I and Periyasamy, K and Gladnikoff, M and Joseph, B and Mayer, R and Aminov, E},
title = {Targeted Intracellular Metal Modulation Attenuates Oxidative Stress and Preserves Retinal Integrity and Function in a Zebrafish Model of Mitochondrial Dysfunction and Age-Related Retinal Degeneration.},
journal = {International journal of molecular sciences},
volume = {27},
number = {18},
pages = {},
pmid = {42794693},
issn = {1422-0067},
mesh = {Animals ; *Oxidative Stress/drug effects ; Zebrafish ; *Mitochondria/metabolism/drug effects/pathology ; Disease Models, Animal ; Humans ; *Retinal Degeneration/metabolism/pathology/drug therapy ; *Retina/metabolism/pathology/drug effects ; Retinal Pigment Epithelium/metabolism/drug effects ; Iron/metabolism ; Zinc/metabolism ; Reactive Oxygen Species/metabolism ; Epigenesis, Genetic/drug effects ; Macular Degeneration/metabolism ; *Metals/metabolism ; },
abstract = {Retinal degeneration is associated with mitochondrial dysfunction, oxidative stress, and disruption of metal homeostasis within the retinal pigment epithelium (RPE). Dysregulation of redox-active metals has been implicated in age-related macular degeneration (AMD), but whether targeted intracellular metal modulation preserves retinal structure and function remains incompletely understood. This study explores the effect of metal ion modulation on retinal structure and visual function. Telomir-Zn, a Zinc-based intracellular metal modulator, depletes labile Fe[2+], potently inhibits multiple JmjC KDMs, and induces epigenetic reprogramming. In a zebrafish model combining impaired DNA repair with accelerated mitochondrial oxidative stress and progressive retinal degeneration (Sen57^wrn-/-^ND6^-/+^), Telomir-Zn reduced oxidative stress, preserved retinal architecture, improved visual behaviors, and partially normalized telomeric content and CpG methylation patterns. Complementary studies in human ARPE-19 RPE cells showed attenuation of iron/copper-induced ROS and calcium dysregulation, with reciprocal zinc accumulation and labile Fe[2+] depletion. These findings suggest that targeted metal modulation and multi-KDM inhibition may be a novel strategy to mitigate oxidative-epigenetic stress to preserve retinal structure/function in degenerative disease, supporting further investigation and development for AMD.},
}

Animals
*Oxidative Stress/drug effects
Zebrafish
*Mitochondria/metabolism/drug effects/pathology
Disease Models, Animal
Humans
*Retinal Degeneration/metabolism/pathology/drug therapy
*Retina/metabolism/pathology/drug effects
Retinal Pigment Epithelium/metabolism/drug effects
Iron/metabolism
Zinc/metabolism
Reactive Oxygen Species/metabolism
Epigenesis, Genetic/drug effects
Macular Degeneration/metabolism
*Metals/metabolism

@article {pmid42795729,
year = {2026},
author = {Ruiz-Moreno, JM and Bernal-Morales, C and Esteban-Floría, O and Rodríguez-de-la-Rúa, E and Remolí-Sargues, L and Borras-Blasco, J and Gómez-Benlloch, A and Cilveti, E and Valsero-Franco, S and Arriola-Naharro, C and García-Lunar, P and Kaminski-Santamaría, S and Muñoz-Molina, B and García-Layana, A},
title = {From Trials to Treatment: Current Evidence Supporting Faricimab Use in nAMD and DME.},
journal = {Journal of clinical medicine},
volume = {15},
number = {18},
pages = {},
pmid = {42795729},
issn = {2077-0383},
support = {//Roche Farma S.A./ ; },
abstract = {Neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) are leading causes of visual impairment and require long-term intravitreal anti-vascular endothelial growth factor (VEGF) therapy. However, treatment burden and suboptimal real-world outcomes remain major challenges. Faricimab is a bispecific monoclonal antibody that simultaneously inhibits VEGF-A and angiopoietin-2 (Ang-2), a key mediator of vascular destabilization, leakage and inflammation, offering a novel dual-pathway approach aimed at improving efficacy and durability. This narrative review summarizes evidence from pivotal clinical trials and recent real-world studies evaluating the efficacy, durability, and safety of faricimab in patients with nAMD and DME. Real-world evidence from international cohorts and emerging data from Spanish routine clinical practice largely corroborate previous findings, showing anatomical improvements, stable or improved visual outcomes, and reduced treatment burden in treatment-naïve and previously treated eyes. Overall, the evidence reviewed indicates that faricimab is an effective and well-tolerated therapeutic option that may help address unmet needs in the long-term management of nAMD and DME. Importantly, data from real-world clinical practice are consistent with findings from pivotal trials, supporting the translation of faricimab's outcomes into routine care.},
}

@article {pmid42798083,
year = {2026},
author = {Wang, L and Lu, Y and Tang, H},
title = {Knowledge, attitudes, and practices regarding age-related macular degeneration among adults aged 30 years and above: A cross-sectional study.},
journal = {Medicine},
volume = {105},
number = {39},
pages = {e50700},
doi = {10.1097/MD.0000000000050700},
pmid = {42798083},
issn = {1536-5964},
support = {SWFZ23-C-95//Research Project of the Sichuan Provincial Primary Health Development Research Center/ ; },
mesh = {Humans ; *Health Knowledge, Attitudes, Practice ; Cross-Sectional Studies ; Female ; Male ; *Macular Degeneration/psychology/epidemiology ; Adult ; Middle Aged ; Surveys and Questionnaires ; Aged ; China/epidemiology ; Risk Factors ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision impairment. Although modifiable risk factors accumulate early in life, current research predominantly focuses on older adults. This study aimed to assess the levels of knowledge, attitudes, and practices regarding AMD among adults aged 30 years and above in Nanchong, Sichuan Province, China. A cross-sectional study was conducted between November 2023 and August 2024 at Nanchong Central Hospital among adults aged 30 years and above, employing a validated and self-designed questionnaire (Cronbach's α = 0.838). The survey collected demographic data and measured scores for knowledge, attitudes, and practices. Participants were recruited through convenience sampling from outpatients in the ophthalmology department. The study included 424 participants, with 48 (11.32%) diagnosed with AMD. The mean knowledge, attitude, and practice scores were 5.41 ± 5.20 (range = 0-22), 32.43 ± 4.15 (range = 9-45), and 20.74 ± 5.01 (range = 7-35), respectively. Significant positive correlations were observed between knowledge and attitude (r = 0.423, P < .001), knowledge and practice (r = 0.576, P < .001), and attitude and practice (r = 0.492, P < .001). Mediation analysis indicated that knowledge exerted significant direct effects on attitude (β = 0.435, P = .020) and practice (β = 0.719, P = .012). Attitude also showed a significant direct effect on practice (β = 0.360, P = .004). In addition, a significant indirect effect of knowledge on practice through attitude was observed (β = 0.156, P = .005), confirming the mediating role of attitude. Overall, the participants demonstrated low levels of AMD knowledge, moderately positive attitudes, and inactive practices. These findings underscore the need to move beyond simply increasing AMD awareness toward promoting sustained preventive eye health behaviors among adults aged 30 years and above. Integrating practical risk-reduction guidance and appropriate eye-care practices into public health education may help facilitate earlier recognition of AMD risk and more proactive eye health management.},
}

Humans
*Health Knowledge, Attitudes, Practice
Cross-Sectional Studies
Female
Male
*Macular Degeneration/psychology/epidemiology
Adult
Middle Aged
Surveys and Questionnaires
Aged
China/epidemiology
Risk Factors
Aged, 80 and over

@article {pmid42793711,
year = {2026},
author = {Amine, R and Mizuno, M and Matar, K and Indurkar, A and Simoes, P and Hu, M and Downes, RA and Talcott, KE and Reese, JL and Ehlers, JP},
title = {The Structure-Function Link of Ellipsoid Zone Integrity and Outer Retinal Features with Visual Acuity in Dry AMD.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {18},
pages = {},
pmid = {42793711},
issn = {2075-4418},
abstract = {Background/Objectives: The purpose of this study was to evaluate associations between quantitative ellipsoid zone (EZ) integrity metrics derived from spectral-domain OCT (SD-OCT) and visual outcomes, including clinically meaningful visual acuity (VA) loss, in dry age-related macular degeneration (AMD). Methods: This single-center retrospective image-analysis cohort included 351 eyes from 351 patients with intermediate AMD or atrophic changes. Macular SD-OCT scans were analyzed using a certified-reader-validated machine learning-based segmentation platform to delineate the EZ, retinal pigment epithelium (RPE), and Bruch's membrane (BM). EZ metrics included EZ-RPE thickness (i.e., outer segment thickness) and EZ attenuation, defined as partial attenuation (EZ-RPE thickness of ≤20 µm, abnormal outer segment thinning)) or total attenuation/loss (0 µm). Drusen volume was quantified from the RPE-BM compartment. VA was converted to ETDRS letters. Associations between baseline OCT metrics and baseline VA, Year 2 VA, and ≥15-letter VA loss were assessed using nonparametric testing, linear regression, and ANCOVA. Results: Greater EZ-RPE thickness and lower EZ attenuation were associated with better baseline VA (all p < 0.001), and EZ metrics remained significant in cross-sectional regression models. Among 188 eyes with Year 2 follow-up, 38 (20%) experienced ≥15-letter VA loss. These eyes had significantly lower baseline EZ-RPE thickness (i.e., abnormal outer segment thinning) and greater EZ attenuation than eyes without such loss (all p < 0.001). In ANCOVA models, EZ metrics remained associated with Year 2 VA (all p < 0.001), whereas drusen volume was not. Conclusions: Quantitative EZ integrity metrics were associated with cross-sectional and longitudinal visual outcomes in dry AMD. EZ-RPE thickness and EZ attenuation may serve as clinically relevant OCT biomarkers reflecting photoreceptor integrity and risk of meaningful VA loss.},
}

@article {pmid42783204,
year = {2026},
author = {Salvetat, ML and Pellegrini, F and Zeppieri, M and Capobianco, M and Avitabile, A and Cannizaro, L and Gagliano, G and Cappellani, F and Gagliano, C},
title = {Iontophoresis Drug Delivery to the Macula of Lutein for Age Related Macular Degeneration.},
journal = {Diseases (Basel, Switzerland)},
volume = {14},
number = {9},
pages = {},
pmid = {42783204},
issn = {2079-9721},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) represents a leading cause of irreversible vision loss worldwide, driven by intricate interactions among oxidative stress, low-degree chronic inflammation, and macular pigment depletion in aging retinas. Lutein, a component of the macular pigment, has attracted significant attention in AMD management for its antioxidant and blue-light filtering properties. Its oral supplementation, however, although showing potential in slowing AMD progression, requires daily intake and results in variable macular absorption. Trans-scleral iontophoresis (TSI) is a non-invasive technique using low-intensity electric currents to deliver charged molecules into biological tissues and represents an innovative method to deliver lutein into the retina.

METHODS: The present narrative review synthesizes and discusses the results of lutein supplementation in AMD patients; the ocular iontophoresis basal principles, efficacy, safety and limitations in treating different ophthalmic pathologies; and the evolving clinical evidence supporting lutein TSI in the AMD management.

RESULTS: Ex-vivo studies have shown that lutein TSI may provide efficient, localized, rapid, and sustained retinal supplementation of macular pigment, overcoming oral intake limitations. Recent preliminary clinical studies have demonstrated that this technique is well-tolerated and effective in enhancing macular pigment optical density and improving some visual functions in AMD patients.

CONCLUSIONS: Ex-vivo and pilot clinical studies highlight the capacity of TSI to deliver lutein inside the retina, overcoming physiological barriers that may limit the efficacy of lutein oral administration. The demonstration of the efficacy of the procedure in preserving/improving visual functions and delaying disease progression in AMD patients requires further long-term randomized controlled clinical studies.},
}

@article {pmid42784432,
year = {2026},
author = {Chang, JT and Chien, HW and Lee, TY and Wang, K and Huang, CH},
title = {Real-World Outcomes of Faricimab Versus Aflibercept in Treatment-Naïve Neovascular Age-Related Macular Degeneration with Pigment Epithelial Detachment.},
journal = {Seminars in ophthalmology},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/08820538.2026.2735013},
pmid = {42784432},
issn = {1744-5205},
abstract = {PURPOSE: To compare the real-world early outcomes of faricimab versus aflibercept 2 mg in Asian patients with treatment-naïve neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV), focusing on retinal pigment epithelial detachment (RPED) reduction.

METHODS: This retrospective study included treatment-naïve nAMD or PCV eyes with baseline RPED receiving three consecutive monthly loading injections of aflibercept or faricimab. Best-corrected visual acuity, central macular thickness (CMT), intraretinal or subretinal fluid, maximum RPED height, and RPED improvement ratio were assessed at baseline and after treatment. RPED was classified as fibrovascular or serous/mixed by optical coherence tomography.

RESULTS: Fifty-eight eyes were included: 27 treated with faricimab and 31 with aflibercept. Both aflibercept and faricimab had significantly reduced CMT (-99.7 ± 101.2 and -129.6 ± 109.3 μm; both p < .001) and maximum RPED height (-99.4 ± 205.6 and -151.4 ± 183.5 μm; p = .011 and <0.001, respectively). In the fibrovascular RPED subgroup, the RPED improvement ratio was significantly greater with faricimab (35.6% vs. 16.5%; p = .029). Serous component resolution was also more frequent with faricimab (100% vs 61.5%; p = .045).

CONCLUSIONS: Both treatments improved retinal anatomy, while faricimab produced greater fibrovascular RPED height reduction and more complete serous component resolution.},
}

@article {pmid42786857,
year = {2026},
author = {Shahsuvaryan, ML},
title = {Metformin as an Emerging Candidate for Diabetic Retinopathy, Agerelated Macular Degeneration and Glaucoma Pharmacotherapy: Evidence and Perspectives.},
journal = {Current reviews in clinical and experimental pharmacology},
volume = {},
number = {},
pages = {},
doi = {10.2174/0127724328519947260917114932},
pmid = {42786857},
issn = {2772-4336},
abstract = {Varying degrees of visual impairment up to complete blindness are widespread and represent a public health problem with a highly demarсated escalation. Currently, the leading causes of blindness are Diabetic Retinopathy (DR), Age-Related Macular Degeneration (AMD), and glaucoma, with an obvious exponential enlargement of vulnerable population groups as a result of urbanization followed by lifestyle changes and growth of the aging population. Management of these diseases is still challenging. The development of intraocular therapy with antiangiogenics or Vascular Endothelial Growth Factor inhibitors (anti-VEGF) opens a new avenue in eye disease treatment; however, despite these advances, new concerns are raised. DR, AMD, and glaucoma represent diseases with bilateral involvement, which underscores a need for oral systemic preventive therapy targeting both eyes simultaneously, as a cost-effectively optimized approach. At the same time, there is a need for a multi-target drug with preventive and therapeutic potential not only for eye diseases, but also for systemic diseases in patients with multimorbidity. Continued research has the potential to enhance druggability of the leading causes of blindness. A growing body of evidence suggests that metformin, as a drug with multimodal activity, has good preventive and therapeutic potential, opening a new avenue in ocular pharmacotherapy.},
}

@article {pmid42787462,
year = {2026},
author = {Guymer, RH and Wu, Z and Gao, SS and Zhang, M and Steffen, V and Chen, C and Zhang, J and Litts, KM and Chang, MC and Elstrott, J and Yaspan, B and Datta, S and Willis, JR and Liu, L and Chen, H and , },
title = {HONU: A Multicenter, Prospective, Observational Study of the Progression of Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101320},
pmid = {42787462},
issn = {2666-9145},
abstract = {PURPOSE: Large and lengthy clinical trials are currently required to study the efficacy of interventions aiming to slow the progression of the early stages of age-related macular degeneration (AMD). To enable the design of more feasible trials, an observational study HONU aims to comprehensively study eyes with intermediate AMD (iAMD) to explore novel clinical endpoints and patient enrichment strategies.

DESIGN: Prospective, multicenter, international observational study.

PARTICIPANTS: Four hundred patients, whose study eye is required to have large drusen and pigmentary change, but without evidence of any atrophic changes other than incomplete retinal pigment epithelium and outer retinal atrophy. The nonstudy eye is required to have some evidence of atrophy.

METHODS: Patients are assessed every 12 weeks for up to 36 months, with standard opthalmic examinations and multimodal retinal imaging as well as a range of novel visual functional tests. Patient-reported outcomes and biomarker samples are also collected. Structural changes on multimodal imaging are evaluated longitudinally and their relationship with visual function parameters analyzed. Exploratory interim analyses are planned.

MAIN OUTCOME MEASURES: The rates of conversion from baseline high risk iAMD to more advanced atrophic AMD stages, and the rate of ellipsoid zone loss.

RESULTS: Recruitment commenced in May 2022 and 400 patients were enrolled by August 2024, allowing for up to 3 years follow-up. Enrollment occurred at 72 sites across 6 countries. The median age of the patients at baseline was 75 years, ranging from 50 to 93 years. The cohort is predominantly female, making up 69% of patients, and 95% identified as White.

CONCLUSIONS: HONU will provide critical and robust natural history data on AMD progression in patients with high-risk iAMD in the study eye. Potential novel earlier clinical trial endpoints and enrichment strategy for high-risk patients will be determined. Knowledge gained will inform design and feasibility of early interventional studies aiming to slow progression to vision-threatening late AMD.

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

@article {pmid42787488,
year = {2026},
author = {Maass, KF and Maia, M and Gune, S and Chang, MC},
title = {Pharmacodynamics of Free VEGF After Treatment with the Port Delivery Platform with Ranibizumab in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101367},
pmid = {42787488},
issn = {2666-9145},
abstract = {OBJECTIVE: To evaluate the pharmacodynamics of aqueous humor (AH) free VEGF concentrations after treatment with the Port Delivery Platform with ranibizumab (PDS) in patients with neovascular age-related macular degeneration (nAMD).

DESIGN: Pharmacokinetic and pharmacodynamic analyses from the phase III Archway (NCT03677934) and phase II Ladder (NCT02510794) trials.

PARTICIPANTS: Patients with treatment-responsive nAMD.

METHODS: In Archway, patients received PDS 100 mg/mL with refills every 24 weeks (Q24W) or intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W) for 96 weeks. In Ladder, patients received PDS 10, 40, or 100 mg/mL with refills based on protocol-defined criteria or intravitreal ranibizumab 0.5 mg Q4W. Aqueous humor samples were collected throughout the trials (PDS arms only in Ladder) in a subset of patients.

MAIN OUTCOME MEASURES: Aqueous humor ranibizumab and free VEGF concentrations.

RESULTS: Archway analyses included 1149 AH samples from 215 patients. Ladder analyses included 109 AH samples from 47 patients. Aqueous humor ranibizumab concentrations after treatment with the PDS were consistent with the PDS implant release rate. Median AH free VEGF concentrations at randomization (on average 3 weeks after intravitreal ranibizumab injection) were 8.46 and 7.26 pg/mL in the PDS 100 mg/mL and intravitreal ranibizumab Q4W arms, respectively. Throughout the trial, AH free VEGF concentrations remained suppressed in both arms relative to previously reported values from treatment-naïve patients, and AH free VEGF concentrations 24 weeks after treatment with PDS 100 mg/mL Q24W were similar to or lower than those 4 weeks after treatment with intravitreal ranibizumab. In Ladder, analysis of limited samples suggests there was a tendency for a delayed loss of AH free VEGF suppression with increasing ranibizumab dose. Below AH ranibizumab concentrations of ∼10[6] pg/mL, there was a negative correlation between AH free VEGF and AH ranibizumab concentration. There were no correlations between AH free VEGF concentrations and clinical outcomes in either arm, including change from baseline in best-corrected visual acuity and central subfield thickness at week 96.

CONCLUSIONS: These findings demonstrate that PDS 100 mg/mL Q24W suppresses AH free VEGF throughout the entire 24-week refill-exchange interval and to an extent similar to that at 4 weeks after intravitreal ranibizumab.

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

@article {pmid42788443,
year = {2026},
author = {Safarpour Lima, B and Sayanjali, S and Shoham-Hazon, N},
title = {Stem Cell-Based Strategies for Retinal Cell Restoration.},
journal = {Biotechnology journal},
volume = {21},
number = {9},
pages = {e70311},
doi = {10.1002/biot.70311},
pmid = {42788443},
issn = {1860-7314},
mesh = {Humans ; *Stem Cell Transplantation/methods ; Animals ; *Stem Cells/cytology ; *Retina/cytology ; *Retinal Degeneration/therapy ; },
abstract = {Retinal degenerative diseases, including age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and inherited retinal dystrophies, are among the leading causes of irreversible vision loss and blindness worldwide. Current treatments primarily slow disease progression and are unable to restore lost retinal cells or visual function, highlighting the need for regenerative therapeutic strategies. Stem cell-based therapies have emerged as a promising approach for retinal repair through multiple mechanisms, including retinal cell replacement, stimulation of endogenous regeneration, cellular reprogramming, immunomodulation, and paracrine signaling. This narrative review provides a comprehensive overview of the major stem cell sources investigated for retinal regeneration. In addition, the roles of extracellular vesicles and retinal organoids as emerging therapeutic platforms are discussed. Particular emphasis is placed on comparing the biological rationale, therapeutic potential, current preclinical and clinical evidence, and translational readiness of each approach. Despite encouraging progress, several challenges continue to limit routine clinical application, including poor survival and integration of transplanted cells, immune rejection, tumorigenicity, genomic instability, variability in differentiation efficiency, manufacturing standardization, and long-term safety. Continued advances in stem cell biology, tissue engineering, gene editing, and clinical trial design are expected to accelerate the development of safe and effective regenerative therapies for retinal diseases.},
}

Humans
*Stem Cell Transplantation/methods
Animals
*Stem Cells/cytology
*Retina/cytology
*Retinal Degeneration/therapy

@article {pmid42788989,
year = {2026},
author = {Kushwah, N and Liu, CH and Bora, K and Maurya, M and Pavlovich, MC and Fu, Z and Kamenecka, TM and Sun, Y and Solt, LA and Chen, J},
title = {Myeloid deficiency of RORα exacerbates lipid dysregulation and laser-induced choroidal neovascularization.},
journal = {Angiogenesis},
volume = {29},
number = {4},
pages = {},
pmid = {42788989},
issn = {1573-7209},
mesh = {Animals ; *Nuclear Receptor Subfamily 1, Group F, Member 1/deficiency/metabolism/genetics ; *Choroidal Neovascularization/metabolism/pathology/genetics/etiology ; *Lipid Metabolism ; *Lasers/adverse effects ; Macrophages/metabolism/pathology ; PPAR gamma/metabolism/genetics ; Mice ; *Myeloid Cells/metabolism/pathology ; Mice, Knockout ; Microglia/metabolism/pathology ; Inflammation/pathology ; },
abstract = {Dysregulated lipid and cholesterol metabolism is implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of vision loss. Retinoic acid receptor-related orphan receptor alpha (RORα) is a lipid-sensing nuclear receptor genetically associated with neovascular AMD. We investigated the role of RORα in regulating AMD-like pathologies and laser-induced choroidal neovascularization (CNV) through mediating myeloid cell lipid homeostasis and function. Both systemic (Rora[sg/sg]) and myeloid-specific (Rora[fl/fl];LysMCre) RORα deficient mice exhibited fundus lesions with aging, and exacerbated CNV with chronic subretinal inflammation, with subretinal accumulation of lipid-laden activated microglia/macrophages, and increased levels of pro-inflammatory cytokines. RORα-deficient macrophages showed enhanced lipid droplet formation and upregulation of peroxisome proliferator-activated receptor gamma (PPARγ), a lipogenic RORα target gene. Pharmacological inhibition of RORα in cultured macrophage recapitulated the effects of RORα deficiency on lipid enrichment and inflammation, whereas PPARγ inhibition in RORα deficient mice partially reversed the effects on laser-induced CNV, lipid accumulation and inflammation. Additionally, migratory chemokine receptors, including CX3CR1 and CD47, were downregulated in RORα-deficient myeloid cells, contributing to impaired elimination of inflammatory cells from the subretinal space. These findings identify RORα as a critical transcriptional regulator that links lipid dysregulation to persistent subretinal inflammation and pathological CNV highly relevant in AMD.},
}

Animals
*Nuclear Receptor Subfamily 1, Group F, Member 1/deficiency/metabolism/genetics
*Choroidal Neovascularization/metabolism/pathology/genetics/etiology
*Lipid Metabolism
*Lasers/adverse effects
Macrophages/metabolism/pathology
PPAR gamma/metabolism/genetics
Mice
*Myeloid Cells/metabolism/pathology
Mice, Knockout
Microglia/metabolism/pathology
Inflammation/pathology

@article {pmid42790816,
year = {2026},
author = {Ha, J and Choi, YH and Lee, D and Choi, J and Seo, W and Lee, G and Nam, D and Thakur, S and Yoo, TK and Hwang, S},
title = {A multi-label deep learning system for simultaneous detection of nine fundus conditions.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100379},
doi = {10.1016/j.apjo.2026.100379},
pmid = {42790816},
issn = {2162-0989},
abstract = {PURPOSE: To develop and validate a deep learning model for simultaneous detection of nine fundus conditions from a single color fundus photograph.

METHODS: A development dataset of 236,242 color fundus images was assembled from 17 heterogeneous sources and partitioned at the patient level into training (70%), tuning (10%), and internal validation (20%) sets; 5-fold cross-validation was applied on the training set. Nine target conditions were labeled using standardized or photographic criteria: diabetic retinopathy (DR), age-related macular degeneration (AMD), myopic macular degeneration (MMD), glaucoma suspect (GS), epiretinal membrane (ERM), retinal vascular occlusion (VO), media opacity, retinal hemorrhages, and any retinal disorder (composite). A multitask ConvNeXt architecture was trained end-to-end, with operating thresholds pre-specified via Youden's index on the tuning set. External validation was performed on an independent cohort of 4,055 images from an East Asian health-screening center, excluded from model development.

RESULTS: On internal validation (N = 47,229), AUROCs ranged from 0.943 (AMD) to 0.989 (VO), with sensitivity of 88.1%-97.1% and NPV ≥98.8% for eight of nine conditions. On independent external validation (N = 4,055), AUROCs ranged from 0.894 (retinal disorder) to 0.983 (MMD), with NPV ≥95.6% for eight of nine conditions, including 99.3% for DR, 99.9% for VO, and 99.8% for MMD.

CONCLUSIONS: This study presents a validated, criteria-anchored multi-label fundus triage framework capable of simultaneously screening for nine conditions from a single fundus photograph, with performance maintained on external validation at a source-excluded health-screening site within the same national health-screening system.},
}

@article {pmid42791521,
year = {2026},
author = {Jonas, JB and Panda-Jonas, S and Xue, J and Jonas, RA and Wang, YX},
title = {Shallow and bullous retinal pigment epithelium elevations in age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42791521},
issn = {1471-2415},
mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; Male ; Tomography, Optical Coherence/methods ; Female ; Prevalence ; Middle Aged ; Aged ; *Macular Degeneration/epidemiology/diagnosis/complications ; *Retinal Detachment/epidemiology/diagnosis ; },
abstract = {OBJECTIVE: To assess prevalence and associations of shallow retinal pigment epithelium (RPE) elevations (RPEEs) and bullous RPE detachments (RPEDs).

METHODS: Macular optical coherence tomographic images taken in the population-based Beijing Eye Study were examined for the presence of RPEEs/RPEDs.

RESULTS: In the study cohort of 953 eyes (mean age:63.3 ± 9.3years), RPEE/RPED prevalence increased from 0/376 (0%) in the normal group and 0/373 (0%) in the group with early AMD stage, to 33/199 (16.6%;95%CI:11.4,21.8) and 1/5 (20.0%;95%CI:0.0,75.5) in intermediate and late AMD, respectively. In intermediate AMD, prevalences of RPEEs and RPEDs were 30/199 (15.1%;95%CI:10.0,20.2) and 9/199 (4.5%;95%CI:1.5,7.5), respectively. Higher total RPEE/RPED prevalence was associated with higher AMD stage (OR:55.3;95%CI:14.4,327;P < 0.001), higher drusen number (OR:1,05;95%%CI:1.02,1.07;P < 0.001), lower prevalence of external limiting membrane defects (OR:0.19;95%CI:0.05,0.57;P = 0.003), in addition to male sex (OR:11.0;95%CI:3.37,45.5;P < 0.001) and higher serum concentration of triglycerides (OR:1.48;95%CI:1.20,1.89;P < 0.001). RPEE/RPED prevalence was not significantly associated with choroidal thickness as a whole (P = 0.55) or separated in a large-vessel choroidal layer (P = 0.86), medium-sized vessel layer (P = 0.66) or small-vessel layer (P = 0.24), prevalence (P = 0.97) and location of any intraretinal hyperreflective foci, and prevalence of reticular pseudodrusen (P = 0.57).

CONCLUSIONS: Any RPEE/RPED, RPEEs and RPEDs were found in 16.6%, 15.1% and 4.5% of eyes with intermediate AMD, respectively, with a higher RPEE/RPED prevalence correlating with higher drusen number, lower prevalence of external limiting membrane defects and higher serum concentration of triglycerides. The statistical independence of RPEEs/RPEDs from the prevalences of reticular pseudodrusen and intraretinal hyperreflective foci point to differences in their etiologies.},
}

Humans
*Retinal Pigment Epithelium/pathology
Male
Tomography, Optical Coherence/methods
Female
Prevalence
Middle Aged
Aged
*Macular Degeneration/epidemiology/diagnosis/complications
*Retinal Detachment/epidemiology/diagnosis

@article {pmid42792179,
year = {2026},
author = {Krekora, J and Drożdż, J and Blasiak, J and Kaarniranta, K},
title = {From Retina to Vasculature: Oxidative Stress as a Common Mechanistic Link Between Age-Related Macular Degeneration and Cardiovascular Disease.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/antiox15091140},
pmid = {42792179},
issn = {2076-3921},
abstract = {Increasing epidemiological and experimental evidence suggests that age-related macular degeneration (AMD) and cardiovascular disease (CVD) share multiple pathogenic mechanisms. Among these, oxidative stress has emerged as one of the most plausible links connecting retinal degeneration and cardiovascular pathology. Excessive production of reactive oxygen and nitrogen species, combined with declining antioxidant defenses, contributes to lipid peroxidation, mitochondrial dysfunction, chronic inflammation, complement activation, cellular senescence, and impaired cellular stress responses in both the retina and the vascular system. Notably, drusen (AMD) and atherosclerotic plaques (CVD) share several molecular constituents. Therefore, AMD and CVD may represent tissue-specific manifestations of broader age-related disturbances in redox homeostasis and inflammatory regulation. Nevertheless, the coexistence of AMD and CVD is incomplete, suggesting that genetic susceptibility, tissue-specific responses to oxidative stress, biological aging, and mechanisms of cellular resilience influence disease expression. In this review, we summarize current evidence linking AMD and CVD, examine oxidative stress-driven molecular pathways common to both disorders, discuss emerging biomarkers and therapeutic targets, and highlight important unresolved questions regarding disease heterogeneity and causal relationships. A better understanding of the shared mechanisms underlying AMD and CVD may facilitate the development of integrated preventive strategies, improved risk stratification, and more personalized therapeutic approaches for age-related diseases.},
}

@article {pmid42793059,
year = {2026},
author = {Fang, YL and Hsu, YJ and Sung, CH and Kung, CC and Shiu, SR and Hung, CY and Chen, MJ and Chang, DC and Liang, IC and Hung, CF},
title = {Cynarin Alleviates Sodium Iodate-Induced Retinal Pigment Epithelium Injury by Regulating Oxidative Stress and Inflammation.},
journal = {Biomolecules},
volume = {16},
number = {9},
pages = {},
doi = {10.3390/biom16091227},
pmid = {42793059},
issn = {2218-273X},
support = {111-SHK-FJU-02//Shin Kong WHS Memorial Hospital/ ; TSGH_D_113127//Tri-Service General Hospital/ ; },
mesh = {*Iodates/toxicity ; *Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/drug effects/metabolism/pathology/injuries ; Animals ; Humans ; Mice ; *Inflammation/drug therapy/metabolism/chemically induced/pathology ; NF-kappa B/metabolism ; Cell Survival/drug effects ; Mice, Inbred C57BL ; Cell Line ; Macular Degeneration/drug therapy/chemically induced/metabolism ; *Pyrans/pharmacology ; Cytokines/metabolism ; Signal Transduction/drug effects ; },
abstract = {Background: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss and is strongly driven by oxidative stress and inflammation. This study investigated the protective effects of cynarin against sodium iodate (NaIO3)-induced retinal pigment epithelium (RPE) injury, focusing on the MAPK and NF-κB signaling pathways. Materials and Methods: Human ARPE-19 cells were exposed to NaIO3, and cell viability was assessed by the MTT assay. Protein expression of MAPK components (p38, JNK, ERK) and the NF-κB pathway was analyzed by Western blotting, and pro-inflammatory cytokine (IL-1β, IL-6, TNF-α) mRNA expression was measured by RT-qPCR. In vivo, NaIO3-induced retinal degeneration in C57BL/6 mice was treated with cynarin (3 or 10 mg/kg) for seven days, and retinal changes were evaluated by fundus photography, fluorescein angiography, and OCT. Results: Cynarin preserved ARPE-19 cell viability without cytotoxicity. It significantly attenuated NaIO3-induced p38 and JNK phosphorylation, IκB degradation, and NF-κB activation while downregulating IL-1β, IL-6, and TNF-α expression. In vivo, cynarin reduced drusen-like lesions, hyperfluorescent abnormalities, and retinal thinning, and dose-dependently suppressed ocular pro-inflammatory cytokines. Conclusions: Cynarin protects against oxidative stress-induced retinal degeneration by suppressing MAPK and NF-κB inflammatory signaling, representing a promising therapeutic candidate for preventing or delaying NaIO3-induced dry AMD-like retinal injury.},
}

*Iodates/toxicity
*Oxidative Stress/drug effects
*Retinal Pigment Epithelium/drug effects/metabolism/pathology/injuries
Animals
Humans
Mice
*Inflammation/drug therapy/metabolism/chemically induced/pathology
NF-kappa B/metabolism
Cell Survival/drug effects
Mice, Inbred C57BL
Cell Line
Macular Degeneration/drug therapy/chemically induced/metabolism
*Pyrans/pharmacology
Cytokines/metabolism
Signal Transduction/drug effects

@article {pmid42776856,
year = {2026},
author = {Rizzo, S and Sasso, P and Nepita, I and Francione, G and Caputo, CG and Ferrara, M and Feo, A and Savastano, A and Vidal-Aroca, F and Belousov, V and Romano, MR},
title = {First-in-Human Implantation of an Add-On Dual Intraocular System Combining a Standard IOL and the SING-IMT™ Telescope: Optical Simulation, Preclinical Validation, and Clinical Feasibility.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000005023},
pmid = {42776856},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate a dual-implant system combining a capsular-bag monofocal intraocular lens with a sulcus-implanted small-incision new-generation implantable miniature telescope (SING-IMT).

METHODS: Optical simulations quantified retinal spot size, modulation transfer function (MTF), and tolerance to misalignment. Preclinical porcine experiments evaluated surgical feasibility, anatomical stability, and early safety. First-in-human (FiH) implantation assessed surgical outcomes, anterior segment behaviour using ultrasound biomicroscopy and optical coherence tomography, functional vision, and safety over 6 months.

RESULTS: Optical modelling demonstrated that the dual-implant configuration maintained retinal image quality within the rehabilitative regime for advanced AMD, with root-mean-square retinal spot radii of 18.7 µm (0°) and 20.4 µm (2.5°), below the estimated retinal sampling limit (∼49 µm), consistent with an expected visual acuity improvement of approximately 2 Snellen lines. Decentration up to 0.5 mm was optically well tolerated, whereas tilt produced rapid mid-frequency contrast loss. In vivo porcine studies confirmed stable sulcus seating without disruption of the capsular-bag IOL or anterior segment structures. FiH implantation was completed without intraoperative complications. At 6 months, distance visual acuity improved from 20/200 to 20/125, near acuity from 56 to 15 Colenbrander units, and reading speed from non-assessable preoperatively to 20 words/min, with no device-related adverse events.

CONCLUSION: This integrated evaluation supports the feasibility and short-term safety of sulcus-based SING-IMT implantation as a minimally invasive intraocular magnification strategy for selected pseudophakic patients with advanced AMD.},
}

@article {pmid42777504,
year = {2026},
author = {Liu, J and Hu, J and Li, Y and Hu, N and Wang, Y and Chang, B and Guo, Y and Li, X and Zhang, Q and Ming, Y and Lin, C and Ji, H and Yang, Z and Tang, J},
title = {Corrigendum to "Microneedle-Mediated Biomimetic Nanoparticles for Targeted Antioxidant and Anti-Inflammatory Therapy in AgeRelated Macular Degeneration" [J. Control. Release 384(2025) 113908]".},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {399},
number = {Pt A},
pages = {115369},
doi = {10.1016/j.jconrel.2026.115369},
pmid = {42777504},
issn = {1873-4995},
}

@article {pmid42777948,
year = {2026},
author = {Teo, KYC and George, LM and Forouhari, A and Fu, DJ and Sivaprasad, S and Fenner, B and Esmaeelpour, M and Herrmann, R and Cheung, CMG},
title = {Predictors of Geographic Atrophy Growth and Visual Decline in a longitudinal Asian cohort.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.09.020},
pmid = {42777948},
issn = {2468-6530},
abstract = {PURPOSE: To characterize GA growth and visual outcomes in Asian eyes with geographic atrophy (GA) secondary to age-related macular degeneration and to evaluate the incremental prognostic value of deep learning-derived optical coherence tomography (OCT) biomarkers.

DESIGN: Prospective longitudinal observational cohort study.

PARTICIPANTS: One hundred fifty-five eyes of 139 patients with GA and 12-month follow-up.

METHODS: Participants underwent baseline and month-12 multimodal imaging with fundus autofluorescence (FAF) and spectral-domain OCT. GA area was quantified on FAF. A validated deep learning algorithm segmented retinal pigment epithelium layer loss (RPEL), photoreceptor degeneration (PRD), hypertransmission (HTR), and retinal pigment epithelium and outer retinal atrophy (RORA). Layer-specific excess metrics beyond RORA were derived. Multivariable mixed-effects models were constructed to identify predictors of GA growth and month-12 best-corrected visual acuity (VA), with nested models assessing incremental value beyond conventional demographic and imaging features.

MAIN OUTCOME MEASURES: Twelve-month change in GA area and month-12 VA.

RESULTS: Mean baseline GA area was 3.89±4.24 mm[2] and increased by 0.83±0.92 mm[2] at month 12 (P<0.01). In lesions with baseline area ≥2.5mm[2], one year growth rate was 1.32 ± 0.96 mm[2]. Baseline GA area, multifocality, and subretinal drusenoid deposits (SDD) were independently associated with faster growth. When analysed by baseline GA area, SDD were associated with increased growth in eyes with smaller baseline GA area (<2.5mm[2]). PRD-RORA excess was independently associated with GA growth and provided incremental predictive value beyond conventional predictors (ΔR[2]=0.02, P=0.04). Predictors differed by baseline lesion size. Mean VA decreased minimally from 0.68±0.56 at baseline to 0.72±0.57 logMAR at 1-year (P<0.01). Central 1-mm OCT occupancy measures provided greater explanatory value for month-12 VA than 6-mm OCT occupancy.

CONCLUSIONS: Photoreceptor degeneration extending beyond established atrophy provided modest incremental prognostic information beyond conventional features evaluated. Central 1-mm OCT features showed limited association with month-12 VA and may serve as complementary structural correlates of visual function.},
}

@article {pmid42778294,
year = {2026},
author = {Bantounou, MA and Emfietzoglou, M and Baroutis, KG and Starr, MR and Miller, JW and Vavvas, DG},
title = {Sustained proton-pump inhibitor exposure and incident age-related macular degeneration: a new-user, population-based cohort study.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {3},
pages = {},
doi = {10.1136/bmjophth-2026-002935},
pmid = {42778294},
issn = {2397-3269},
mesh = {Humans ; *Proton Pump Inhibitors/adverse effects ; Aged ; Female ; Retrospective Studies ; *Macular Degeneration/epidemiology/chemically induced/diagnosis ; Incidence ; Male ; Middle Aged ; Aged, 80 and over ; Risk Factors ; },
abstract = {OBJECTIVE: Proton-pump inhibitors (PPIs) may disrupt lysosomal acidification, a pathway implicated in age-related macular degeneration (AMD) pathogenesis. We evaluated whether sustained PPI exposure increased the risk of incident AMD in older adults aged ≥60 years.

METHODS AND ANALYSIS: This retrospective observational cohort study included adults aged ≥60 years with sustained PPI exposure, matched 1:1 to unexposed controls on demographics, overall health, healthcare utilisation, cardiometabolic factors. Participants were identified from electronic health records. Sustained PPI exposure was defined as ≥2 years of cumulative use within 3 years of the first prescription. Fine-Gray models treating death as a competing event estimated subdistribution hazard ratios (sHRs) for AMD within 10 years; cause-specific Cox models provided complementary HRs. Analyses included histamine H2-receptor antagonists (H2-antagonists) as a negative exposure control and active comparator.

RESULTS: Incident AMD occurred in 814/49 796 PPI exposed participants (1.64%) and 668/49 796 controls (1.34%) (overall sHR=1.24, 95% CI 1.12 to 1.38; p<0.001; HR=1.25, 95% CI 1.13 to 1.38, p<0.001). Proportional sHRs were non-constant; sHRs were 1.09 (95% CI 0.91 to 1.29) before 2.5 years and 1.33 (95% CI 1.17 to 1.51) thereafter. For non-exudative AMD, 640 PPI exposed (1.29%) and 510 unexposed (1.02%) participants developed disease (overall sHR=1.28, 95% CI 1.14 to 1.44; p<0.001, HR=1.29, 95% CI 1.14 to 1.44, p<0.001). Among those with non-exudative AMD, 190/2503 PPI-exposed participants (7.59%) and 179/2503 controls (7.15%) progressed to exudative AMD (sHR and HR=1.03, 95% CI 0.84 to 1.26; p=0.802 and p=0.801, respectively). No association was observed between H2-antagonists and AMD (sHR=1.02, 95% CI 0.88 to 1.19; p=0.784; HR=1.03, 95% CI 0.88 to 1.20, p=0.729). Results were consistent in the active-comparator analysis (reciprocal overall sHR=1.24, 95% CI 1.04 to 1.48; p=0.016; HR=1.25, 95% CI 1.05 to 1.49, p=0.012).

CONCLUSION: Sustained PPI exposure was associated with a modestly higher AMD risk, whereas no association was observed with H2-antagonists. The consistency of the active-comparator findings supports the potential specificity of this association and warrants further investigation to determine its clinical implications.},
}

Humans
*Proton Pump Inhibitors/adverse effects
Aged
Female
Retrospective Studies
*Macular Degeneration/epidemiology/chemically induced/diagnosis
Incidence
Male
Middle Aged
Aged, 80 and over
Risk Factors

@article {pmid42779760,
year = {2026},
author = {Shautsova, V and Butt, E and Bhuckory, M and Vu, LM and Pham-Howard, D and Mamchik, V and Galambos, L and An, J and Shin, A and Mathieson, K and Kamins, T and Palanker, D},
title = {Electrodeposited Biocompatible Coatings for 3D Electrodes on Retinal Prostheses.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.09.06.749620},
pmid = {42779760},
issn = {2692-8205},
abstract = {Photovoltaic subretinal prosthesis, PRIMA, provides central vision to patients blinded by age-related macular degeneration, with acuity matching the 100 μm pixel size. Further miniaturization requires pillar electrodes to position the stimulating surfaces closer to the inner retinal neurons. While such structures can be electroplated in gold and coated on their tops with SIROF, the exposed gold sidewalls are not biocompatible. Sputtering or atomic layer deposition of protective coatings are unsuitable for selectively passivating the pillar structures without also coating the photosensitive regions and return electrodes of the implant. Here, we present a strategy for biocompatible coating of pillar sidewalls while preserving surrounding implant functionality. The approach combines non-critical photoresist lithography to protect planar return electrodes with electrodeposition of TiO2 or Pt onto gold pillar sidewalls. In-vivo studies demonstrated that both TiO2 and Pt coatings are biocompatible and prevent adverse reactions of the retinal tissue to gold. Since specific capacitance of electroplated TiO2 (25 μF/cm[2]) is much lower than that of Pt (240 μF/cm [2]), the former better limits the current from the side walls and ensures that charge injection occurs predominantly through the pillar tops coated with SIROF (∼6 mF/cm[2]). Electrodeposition, combined with noncritical photolithography provides a scalable wafer-level solution for fabrication of biocompatible three-dimensional electro-neural interfaces, addressing a critical bottleneck in bioelectronics.},
}

@article {pmid42783183,
year = {2026},
author = {Tam, HM and Wang, SY and Sun, YS and Lo, KY},
title = {A Microfluidic Gradient Platform for High-Throughput Evaluation of Blue-Light-Induced Oxidative Stress and Antioxidant Protection in Retinal Pigment Epithelial Cells.},
journal = {Biosensors},
volume = {16},
number = {9},
pages = {},
pmid = {42783183},
issn = {2079-6374},
support = {NSTC 114-2112-M-030-004-//National Science and Technology Council/ ; NSTC 112-2313-B-002-049-MY3//National Science and Technology Council/ ; NSTC 114-2313-B-002-012-MY3//National Science and Technology Council/ ; },
mesh = {Blue Light ; Humans ; *Retinal Pigment Epithelium/metabolism/drug effects ; *Oxidative Stress/radiation effects/drug effects ; *Antioxidants/pharmacology ; Reactive Oxygen Species/metabolism ; Cell Line ; *Microfluidics ; Epithelial Cells ; },
abstract = {The retinal pigment epithelium (RPE) is a monolayer of cells located between retinal photoreceptors and the choroid, playing a critical role in maintaining visual function by protecting the retina and supporting photoreceptor metabolism. Damage to RPE cells can lead to visual disorders, including macular degeneration. Chronic exposure to high-energy blue light has been shown to elevate intracellular reactive oxygen species (ROS) in RPE cells, causing oxidative stress and cellular damage. In this study, a microfluidic platform incorporating a gradient-generating structure was developed to establish controllable and stable gradients of blue light intensity and chemical concentrations. This platform was used to investigate the effects of varying blue light intensities and antioxidant concentrations on oxidative stress in human RPE cells ARPE-19. Cells cultured within the microfluidic channels were exposed to different blue light intensities in combination with chemical treatments. Results demonstrated that ROS production increased with higher blue light intensity, whereas higher antioxidant concentrations effectively reduced ROS accumulation, supporting the ability of these antioxidants to attenuate blue-light-induced intracellular oxidative stress. The present microfluidic device enables simultaneous evaluation of multiple conditions within a single experiment, reducing reagent consumption and enhancing experimental efficiency. This in vitro microfluidic platform integrates chemical and light gradients to assess retinal oxidative damage and antioxidant effects, offering significant potential for ophthalmic drug screening and investigations of retinal protective mechanisms.},
}

Blue Light
Humans
*Retinal Pigment Epithelium/metabolism/drug effects
*Oxidative Stress/radiation effects/drug effects
*Antioxidants/pharmacology
Reactive Oxygen Species/metabolism
Cell Line
*Microfluidics
Epithelial Cells

@article {pmid42776232,
year = {2026},
author = {Ach, T and von der Emde, L},
title = {[Ophthalmological care of senior citizens in residential nursing facilities : Care gaps, the TOVIS study and ways to an improved ophthalmological care].},
journal = {Zeitschrift fur Gerontologie und Geriatrie},
volume = {},
number = {},
pages = {},
pmid = {42776232},
issn = {1435-1269},
abstract = {BACKGROUND: Around 800,000 older people live in approximately 16,500 nursing and old people's homes in Germany and this number will continue to rise due to demographic change. Visual impairment and eye diseases in need of treatment are among the most common yet most neglected health problems in this vulnerable population. This article summarizes the current state of ophthalmological care for nursing home residents in Germany, the barriers involved and the potential contribution of novel tele-ophthalmological care models to closing this care gap.

MATERIAL AND METHODS: Narrative review based on a selective literature search (PubMed, Google Scholar, professional society documents) on ophthalmological care of institutionalized older people with particular focus on the German OVIS and SÄVIP studies, the international literature on prevalence and care models in nursing homes and both published reports on the TOVIS study (TeleOphthalmologische Versorgung In Seniorenheimen).

RESULTS: The OVIS study (2017; n = 600; 32 homes) found an ophthalmological result requiring treatment in 61% of residents, most frequently cataract (53%), age-related macular degeneration (AMD, 39%) and glaucoma (11% suspected); the last ophthalmologist visit occurred on average 4 years earlier. Comparable deficits are described across numerous other countries. The TOVIS pilot study (2023; n = 109 of 139 enrolled residents) tested a telemedical shared-eye-care model in which trained nonmedical personnel performed on-site examinations while ophthalmologists provided remote assessment. A vision-relevant cataract was found in 48.5%, typical AMD lesions in 34.1% and inadequately fitted eyeglasses in 60.6%; only 31.2% of the examined residents were aware of their diagnosis. At 6‑month follow-up only 14 of 52 residents (26.9%) with a referral recommendation actually attended a specialist appointment, despite over 80% rating the tele-examination positively.

CONCLUSION: Ophthalmological care in German nursing homes has been insufficient for years, a pattern that is consistently mirrored across numerous other healthcare systems in the international literature. Tele-ophthalmological shared-eye-care models such as TOVIS are feasible and well accepted but do not by themselves solve the aftercare problem. A substantial gap remains between diagnosis and actual specialist treatment, which requires structured appointment management, transport and accompaniment solutions and closer collaboration between nursing staff, primary care and ophthalmology.},
}

@article {pmid42776254,
year = {2026},
author = {Quarta, A and Sivaprasad, S and Wong, TY and Lanzetta, P and Wykoff, CC and Mastropasqua, R and Sadda, SR},
title = {Ranibizumab port delivery system for neovascular age-related macular degeneration: Current evidence and surgical considerations.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42776254},
issn = {1435-702X},
abstract = {PURPOSE: To review the engineering principles, pharmacokinetics, clinical evidence, surgical considerations, safety profile, and emerging real-world implications of the ranibizumab Port Delivery System (PDS) as a sustained intraocular drug-delivery platform for neovascular age-related macular degeneration.

METHODS: A systematic literature search was conducted to identify peer-reviewed publications addressing implant engineering, molecular compatibility, pharmacokinetics, phase 1-3 trials (LADDER, ARCHWAY, PORTAL), extension studies, perioperative management, safety outcomes, health-economic analyses, and patient-reported outcomes related to the ranibizumab PDS.

RESULTS: Phase 2 and 3 trials demonstrated that PDS delivering ranibizumab 100 mg/mL with fixed 24-week refill intervals achieved visual and anatomic outcomes noninferior to monthly intravitreal injections, with approximately 95% of patients not requiring supplemental treatment before scheduled refills. Pharmacokinetic studies confirmed sustained intraocular drug exposure within the therapeutic window of monthly dosing. Long-term extension data support durability through multi-year follow-up. The distinct safety profile features implant- and conjunctival interface events, including conjunctival erosion, vitreous hemorrhage, and device-associated endophthalmitis, underscoring the importance of surgical technique and postoperative surveillance. Economic analyses indicate cost parity with branded anti-VEGF agents under high injection frequencies, while patient-reported outcomes consistently demonstrate strong preference for sustained delivery. In ARCHWAY, mean BCVA change averaged over Weeks 36/40 was + 0.2 letters with PDS versus + 0.5 letters with monthly ranibizumab, and 98.4% of PDS-treated eyes required no supplemental injections in the first 24-week interval; across later intervals, approximately 95% avoided supplemental treatment before scheduled refill.

CONCLUSIONS: The ranibizumab PDS establishes sustained intraocular anti-VEGF delivery as a viable alternative to anti-VEGF injections especially in patients requiring frequent dosing. Its long-term role will depend on optimization of surgical workflows, management of implant-specific risks, integration of monitoring strategies, and ongoing refinement of device design to support scalable, durable retinal care.},
}

@article {pmid42776803,
year = {2026},
author = {Pařilová, T and Hejsek, L and Hodačová, L},
title = {Discordance Between Eye-Specific Clinical Outcomes and Patient-Reported Visual Function After Faricimab Treatment for Neovascular Age-Related Macular Degeneration: A Two-Case Report.},
journal = {Vision (Basel, Switzerland)},
volume = {10},
number = {4},
pages = {},
pmid = {42776803},
issn = {2411-5150},
support = {Cooperatio, research area HEAS//Charles University/ ; Cooperatio, research area SURG//Charles University/ ; SVV-2025-260776//Ministry of Education Youth and Sports/ ; },
abstract = {Neovascular age-related macular degeneration is a retinal disease of older adults causing central vision loss associated with macular neovascularization. Treatment response is commonly evaluated using visual acuity and retinal morphology. These measures may not fully reflect patient-perceived benefit. We report two older adults with neovascular age-related macular degeneration treated with faricimab who demonstrated discordance between clinical and patient-reported outcomes. In the first case, best-corrected visual acuity changed from 20/200 to 20/180 and central retinal thickness decreased from 480 to 389 µm, whereas the National Eye Institute Visual Function Questionnaire-25 score increased from 33.87 to 60.99 and the exploratory ordinal colour-vividness rating was 25 at baseline and 100 at follow-up. In the second case, best-corrected visual acuity improved from 20/100 to 20/45 and central retinal thickness decreased from 341 to 186 µm, whereas the National Eye Institute Visual Function Questionnaire-25 score declined from 67.08 to 33.17 and the exploratory ordinal colour-vividness rating was 75 at baseline and 25 at follow-up. Changes in patient-reported visual functioning may not always parallel conventional clinical outcomes, while the contrasting exploratory colour-vividness ratings observed in these two cases warrant further investigation.},
}

@article {pmid42776804,
year = {2026},
author = {Gandhi, S and Balas, M and Curtis, R and Zhou, TE and Jin, YP and Yan, P},
title = {Global Ophthalmology Research Output Relative to Disease Burden and National Income, 2011-2021.},
journal = {Vision (Basel, Switzerland)},
volume = {10},
number = {4},
pages = {},
pmid = {42776804},
issn = {2411-5150},
abstract = {PURPOSE: To characterize ophthalmology research output relative to disease burden and national economic capacity after accounting for population size.

METHODS: We analyzed Scopus publications, Global Burden of Disease disability-adjusted life years (DALYs), and World Bank economic and population data from 2011 to 2021. Negative binomial and Gamma models evaluated publication volume and positive citation-weighted impact, adjusting for DALYs, gross domestic product (GDP) per capita, population, disease category, and publication year.

RESULTS: Refractive disorders accounted for 45.4% of DALYs and 23.2% of publication volume; cataract, 44.7% and 29.8%; glaucoma, 5.2% and 30.6%; and age-related macular degeneration, 3.8% and 15.2%. High-income countries accounted for 11.8% of burden, 67.2% of publication volume, and 74.2% of citation-weighted impact; lower-middle-income countries accounted for 49.1%, 7.9%, and 6.8%, respectively. DALYs were not independently associated with publication volume (adjusted count ratio [aCR], 0.99; 95% confidence interval [CI], 0.98-1.01; p = 0.278), whereas GDP per capita (aCR, 4.47) and population (aCR, 13.99) were strongly associated (both p < 0.001). For positive citation-weighted impact, DALYs had a small association (adjusted ratio of means [aRM], 1.05), whereas GDP per capita (aRM, 2.86) and population (aRM, 4.96) were strongly associated (all p < 0.001).

CONCLUSIONS: After accounting for population size, absolute disease burden was not independently associated with publication volume, whereas national economic capacity remained strongly associated with both outcomes. These patterns should inform research and service-delivery priorities.},
}

@article {pmid42769031,
year = {2026},
author = {Liu, W and Hu, Q and Wu, P and Wang, D and Peng, Z and Liu, Z and Chen, X},
title = {Cellular Biological Basis and Novel Breakthroughs in the Pathogenesis of Myopia - A Narrative Review.},
journal = {International journal of general medicine},
volume = {19},
number = {},
pages = {633540},
pmid = {42769031},
issn = {1178-7074},
abstract = {Myopia has evolved into a severe global public health concern, exhibiting an epidemiological trend of earlier onset and higher refractive errors particularly among adolescents. Complications induced by high myopia, such as retinal detachment and macular degeneration, pose grave threats to visual health. This paper is a narrative review. It summarizes advances in the cell biology of myopia, elucidates the mechanisms underlying myopia mediated by multiple intraocular cell types, interprets several interactive regulatory pathways, and reviews biomarkers, targeted interventions and detection technologies. Different from previous reviews, this paper links retinal light signaling, intraocular cross‑tissue communication and scleral remodeling, with a focus on corneal biomechanics and the crosstalk between immunity and aging. It establishes an integrated analytical framework of "retinal phototransduction - trans-tissue cellular communication - scleral matrix remodeling", from which three core mechanistic conclusions are drawn: 1) Myopia is a sterile, chronic low-grade inflammation driven by coordinated dysfunction of multiple ocular tissue cells; cellular senescence and localized inflammation form a positive feedback loop that continuously fuels excessive axial elongation. 2) Retinal glial cells and retinal pigment epithelium serve as relays for visual growth signals. Abnormal defocus disrupts their secretion of cytokines, breaking the homeostasis of scleral collagen synthesis and degradation. 3) The hypoxic microenvironment of the choroid can amplify scleral remodeling and exacerbate myopia progression. Integrating the multilayered signaling regulatory network formed by cells of the cornea, retina and sclera helps clarify the complete pathological logic underlying multicellular synergistic pathogenesis of myopia. It provides mechanistic evidence for the clinical development of an early myopia warning system, tissue-specific targeted pharmaceuticals and stratified individualized prevention and control regimens, and facilitates the shift of myopia intervention from conventional empirical management to a novel precision diagnosis and treatment paradigm grounded in cellular and molecular characteristics.},
}

@article {pmid42769495,
year = {2026},
author = {Moosa, A and Wang, JJ and DeAngelis, MM and Zhang, SX},
title = {The MTRNR2L gene family and age-related macular degeneration.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1925795},
pmid = {42769495},
issn = {1664-3224},
mesh = {Humans ; *Macular Degeneration/genetics/metabolism/pathology ; Animals ; Retinal Pigment Epithelium/metabolism/pathology ; Oxidative Stress ; Multigene Family ; Intracellular Signaling Peptides and Proteins ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of blindness in aging adults, yet no FDA-approved therapies exist for early and intermediate disease. Multiple interconnected pathways, including mitochondrial dysfunction, oxidative stress, and inflammation, contribute to retinal pigment epithelium (RPE) degeneration in AMD, highlighting the need for developing new cytoprotective strategies. The MTRNR2L gene family, comprising nuclear paralogs of mitochondrial-derived peptide humanin, has emerged as a potential regulator of these pathways. Humanin has demonstrated anti-apoptotic, anti-inflammatory, and mitochondrial-stabilizing effects across multiple cell types, including the RPE. Recent transcriptomic and single-cell RNA-sequencing (scRNA-seq) analyses indicate that MTRNR2L genes are upregulated in a variety of human diseases associated with cellular stress response, inflammation, angiogenesis, and neurodegeneration. These findings suggest that MTRNR2L genes participate in coordinated stress-adaptive programs and may mirror humanin's cytoprotective and immunomodulating actions. This review summarizes recent research advances and highlights key gaps for understanding the roles of the MTRNR2L family in RPE protection and AMD progression.},
}

Humans
*Macular Degeneration/genetics/metabolism/pathology
Animals
Retinal Pigment Epithelium/metabolism/pathology
Oxidative Stress
Multigene Family
Intracellular Signaling Peptides and Proteins

@article {pmid42770020,
year = {2026},
author = {Chen, Z and Bach, B and Zhang, H and Wahle, A and Han, IC and Boldt, HC and Russell, SR and Sonka, M and Sohn, EH},
title = {Retinal fluid segmentation in real-world OCT imaging of neovascular AMD using hybrid deep learning and graph-based optimization.},
journal = {Biomedical optics express},
volume = {17},
number = {9},
pages = {4834-4853},
pmid = {42770020},
issn = {2156-7085},
abstract = {Accurate segmentation and quantification of retinal fluid in optical coherence tomography (OCT) images are important for assessing disease activity and treatment response in neovascular age-related macular degeneration (nvAMD). Yet, manual delineation of intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) is labor-intensive and subject to inter-grader variability. We developed a hybrid framework for robust retinal fluid segmentation in clinical-grade longitudinal OCT, combining anatomically constrained retinal-region extraction using Deep LOGISMOS with nnU-Net-based 2-D and 3-D fluid segmentation. To improve adaptation to heterogeneous clinical data while reducing annotation burden, an iterative expert-guided labeling strategy was used, starting with 70 RETOUCH OCT scans and 100 scans from subjects with macular neovascularization at the University of Iowa and expanding to a final aggregated training set of 291 scans. The method was validated on a held-out test set of 50 OCT volumes from 50 nvAMD subjects, with a subset of 20 volumes independently annotated by a second expert for inter-observer analysis. It was further applied to a longitudinal dataset of 14,500 Heidelberg Spectralis macular OCT scans from 221 independent subjects. The ensemble model achieved Dice similarity coefficients (%) of 89.5±11.7 for IRF, 88.0±10.7 for SRF, and 82.0±13.0 for PED against the primary expert annotations, with performance approaching expert-level agreement. In longitudinal inference, our developed framework supports robust large-scale quantification of fluid burden and spatial extent across heterogeneous scan protocols and extended follow-up. The artificial intelligence-based approach has the potential to enable scalable and clinically meaningful longitudinal analysis of retinal fluid in nvAMD.},
}

@article {pmid42770042,
year = {2026},
author = {Kucharczuk, J and Kasprzak, H and Tuchowska-Celej, M and Gawęcki, M},
title = {Incidence and Clinical Course of Intraocular Inflammation Following Pharmacy-Compounded Intravitreal Aflibercept 8mg for Neovascular AMD: A Real-World Cohort Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {643475},
pmid = {42770042},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the incidence and clinical course of intraocular inflammation (IOI) after intravitreal aflibercept 8 mg (Eylea 8 mg - E8) injection in patients with neovascular age-related macular degeneration (nAMD) in Poland.

PATIENTS AND METHODS: This retrospective study included 867 eyes of 867 patients (591 female, 276 male) with nAMD treated with E8 at the 10[th] Military Hospital in Bydgoszcz between January and December 2025. Of these, 655 patients were switched from other intravitreal agents and 212 were treatment-naïve. A total of 3441 E8 injections were administered before IOI onset, with two full 0.07mL (8mg) doses withdrawn from each single-use vial through pharmacy compounding. IOI severity was graded using the Standardization of Uveitis Nomenclature (SUN) criteria, and clinical course and outcomes were analyzed over 6 months of follow-up.

RESULTS: IOI occurred in 20 patients, corresponding to an incidence of 2.31% per eye/patient and 0.58% per injection. Symptoms appeared a mean of 3.3 ± 1.9 days after injection, with decreased visual acuity (BCVA dropped from 0.22 ± 0.10 to 0.58 ± 0.45 logMAR, p=0.0005). All cases were managed with topical corticosteroids, 16/20 additionally received sub-Tenon triamcinolone, and 6 required oral prednisolone; 1 patient required pars plana vitrectomy. Nineteen patients resolved on medical therapy alone, while one patient required surgical intervention (pars plana vitrectomy) to achieve resolution. No retinal vasculitis occurred, and central retinal thickness remained stable during follow-up.

CONCLUSION: In this first Polish cohort study, the incidence of IOI after E8 injection (2.31% per eye/patient) was higher than reported in registration trials, though episodes were generally mild and self-limited, without long-term visual impact. These findings may help inform clinical monitoring for patients receiving E8 for nAMD.},
}

@article {pmid42770455,
year = {2026},
author = {Chinthaginjala, H and E, B and Thriveni, A and Vardhan, KV and Sai Kumar, M and Repollu, M},
title = {Exosomes in Ophthalmology: Bridging Physiological Barriers for Precision Ocular Drug Delivery.},
journal = {Current drug targets},
volume = {},
number = {},
pages = {},
doi = {10.2174/0113894501468995260904090347},
pmid = {42770455},
issn = {1873-5592},
abstract = {INTRODUCTION: Eye disorders such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis persist as prominent contributors to visual impairment on a global scale. Conventional ocular drug delivery systems face a range of physiological hurdles, including tear film clearance, epithelium absorption, conjunctival absorption, and the formidable blood-retinal barrier. These challenges culminate in suboptimal ocular bioavailability, frequently compelling healthcare providers to resort to invasive drug administration methods.

METHODS: This review systematically evaluates recent literature focusing on exosome-based ocular drug delivery systems. Published preclinical and clinical studies were identified through structured searches of PubMed, Scopus, and Web of Science using the keywords "exosomes", "extracellular vesicles", "ocular drug delivery", "retina", and "ophthalmology". The search covered studies published between 2000 and 2025 to understand exosome biology, isolation and characterization techniques, drug-loading strategies, and their ability to overcome ocular physiological barriers.

RESULTS: Exosomes are naturally occurring extracellular vesicles enriched with proteins, lipids, and nucleic acids, exhibiting excellent biocompatibility and intrinsic targeting capabilities. Evidence from preclinical studies demonstrates their ability to traverse ocular barriers and enhance drug retention and bioavailability. Emerging clinical investigations highlight their therapeutic promise in retinal and anterior segment disorders.

DISCUSSION: Compared with synthetic nanocarriers, exosomes offer superior biological stability, reduced immunogenicity, and enhanced tissue penetration. However, challenges related to largescale production, standardization, storage stability, immunological safety, and regulatory approval remain critical barriers to clinical translation.

CONCLUSION: Exosome-based ocular drug delivery represents a promising precision medicine strategy that addresses long-standing limitations of conventional ophthalmic therapies. Continued advances in formulation optimization, scalable manufacturing, and regulatory frameworks are expected to accelerate their clinical and commercial translation for patient-centered eye care.},
}

@article {pmid42770919,
year = {2026},
author = {Chew, EY and Ying, GS and Vitale, S},
title = {Does Cataract Surgery Accelerate the Progression to Late Age-related Macular Degeneration?.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2026.08.036},
pmid = {42770919},
issn = {1549-4713},
}

@article {pmid42771471,
year = {2026},
author = {Park, S and Galdamez, A and Temme, W and Bradley, A and Le, M and Chea, L and Stevenson, E and Gradilla, Y and Lee, EJ and Lin, JH},
title = {Ceapin-A7 Suppresses UPR Signaling and Mitigates Retinal Neovascularization in Vldlr[-/-] Mice.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {18},
pages = {e72300},
doi = {10.1096/fj.202603175R},
pmid = {42771471},
issn = {1530-6860},
support = {P30EY026877//National Institutes of Health (NIH)/ ; R01EY027735//National Institutes of Health (NIH)/ ; R01NS088485//National Institutes of Health (NIH)/ ; I01RX001240/VA/VA/United States ; },
mesh = {Animals ; *Retinal Neovascularization/metabolism/drug therapy/pathology ; *Receptors, LDL/genetics ; Mice ; *Unfolded Protein Response/drug effects ; Activating Transcription Factor 6/metabolism/antagonists & inhibitors/genetics ; *Signal Transduction/drug effects ; Mice, Knockout ; Mice, Inbred C57BL ; Retina/metabolism ; },
abstract = {Pathological neovascularization drives blinding retinal diseases, including diabetic retinopathy, retinopathy of prematurity, and neovascular age-related macular degeneration. Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling are key mechanisms underlying neovascularization. Mice lacking the UPR regulator Activating Transcription Factor 6 (ATF6) show normal retinal vasculature yet are resistant to pathologic neovascularization, suggesting that ATF6 inhibition may mitigate retinal damage and vision loss from aberrant retinal angiogenesis. We tested Ceapin-A7, a selective ATF6 inhibitor, in Vldlr[-/-] mice, a genetic model of retinal neovascularization. Intravitreal Ceapin-A7 reduced ectopic vascular projections into the outer retina and significantly increased scotopic b-wave amplitude, while a-wave and photopic responses showed no significant difference between groups. Single-nucleus RNA sequencing revealed suppressed ATF6/UPR gene programs and angiogenic pathways in retinal endothelial cells and reduced Müller cell gliosis. These findings demonstrate that pharmacologic ATF6 inhibition mitigates retinal neovascularization in Vldlr[-/-] mice and identifies ATF6/UPR as a therapeutic target for neovascular retinal diseases.},
}

Animals
*Retinal Neovascularization/metabolism/drug therapy/pathology
*Receptors, LDL/genetics
Mice
*Unfolded Protein Response/drug effects
Activating Transcription Factor 6/metabolism/antagonists & inhibitors/genetics
*Signal Transduction/drug effects
Mice, Knockout
Mice, Inbred C57BL
Retina/metabolism

@article {pmid42772557,
year = {2026},
author = {Subrahmanian, SM and Sunilkumar, S and Budakoti, S and Yerlikaya, EI and Toro, AL and Barber, AJ and Dennis, MD},
title = {Regulation of Müller glial reprogramming by the stress response protein REDD1 and its limitations in preventing retinal degeneration.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {113583},
doi = {10.1016/j.jbc.2026.113583},
pmid = {42772557},
issn = {1083-351X},
abstract = {Studies here investigated the role of the stress-response protein regulated in development and DNA damage response 1 (REDD1) in Müller glial reprogramming in response to sodium iodate (NaIO3)-induced retinal degeneration. We previously demonstrated that global REDD1 deletion protected mice from NaIO3-induced retinal damage. NaIO3 promoted Müller glial remodeling, characterized by increased levels of glial fibrillary acidic protein (GFAP) and the horizontal orientation of Müller glial processes that localized to areas of retinal degeneration. NaIO3 increased TGF-β1 and mesenchymal gene expression in the retina, including upregulation of N-Cadherin in Müller glia. Retinal gliosis and mesenchymal markers were reduced in the retina of REDD1-deficient mice as compared to wild-type mice after NaIO3 administration, but this was likely secondary to retinal protection. TGF-β signaling was also investigated in human MIO-M1 Müller cell cultures. TGF-β1 increased REDD1 and the expression of gliosis and mesenchymal markers in wild-type Müller cells, and REDD1 deletion reduced TGF-β1-induced mesenchymal marker expression. REDD1 and its downstream effector GSK3β were required for TGF-β1-induced Smad2 linker domain phosphorylation and mesenchymal marker expression. To investigate the role of REDD1-dependent Müller glial reprogramming in retinal protection, NaIO3 was administered to Müller-glia specific REDD1 knockout mice. Müller glia-specific REDD1 deletion attenuated Müller cell remodeling; however, NaIO3-induced retinal damage was similar in Müller glia-specific REDD1 knockout and floxed control mice and visual function was only modestly preserved. The findings support the role of REDD1-dependent signaling in Müller cell reprogramming and implicate a critical role for REDD1 in cells beyond Müller glia in pathological retinal degeneration.},
}

@article {pmid42774045,
year = {2026},
author = {Esser, E and Kuhrt, H and Ziemssen, F and Hollborn, M},
title = {Toll-like receptor 9 in retinal pigment epithelial cells: Expression, function and the role of TGF-β1.},
journal = {Molecular vision},
volume = {32},
number = {},
pages = {210-230},
pmid = {42774045},
issn = {1090-0535},
mesh = {*Retinal Pigment Epithelium/metabolism/cytology/drug effects ; Humans ; *Toll-Like Receptor 9/genetics/metabolism/agonists ; *Transforming Growth Factor beta1/metabolism/pharmacology ; Apoptosis/drug effects ; Cell Proliferation/drug effects ; Cell Hypoxia/drug effects ; Cobalt/pharmacology ; *Epithelial Cells/metabolism/drug effects/cytology ; Signal Transduction/drug effects ; Cell Survival/drug effects ; Gene Expression Regulation/drug effects ; Cell Line ; Toll-Like Receptor Agonists ; Cellular Senescence/drug effects ; RNA, Messenger/genetics/metabolism ; },
abstract = {PURPOSE: Inflammatory processes in the aged retina may be exacerbated by systemic infection with viruses and bacteria, potentially aggravating age-related macular degeneration (AMD). Toll-like receptors (TLR) are key mediators in detecting pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs). This study aimed to investigate TLR gene expression in cultured retinal pigment epithelial (RPE) cells, focusing particularly on TLR9.

METHODS: TLR gene expression was assessed using semiquantitative qPCR, while protein expression was evaluated through western blotting, immunocytochemistry, and ELISA. Hypoxic conditions were simulated using CoCl2 or by incubation in a 0.1% O2 atmosphere. RPE cell proliferation and viability were examined using bromodeoxyuridine (BrdU) and MTT assays. Cell necrosis and apoptosis were analyzed with a cellular DNA fragmentation ELISA.

RESULTS: Among the TLRs analyzed, TLR9 showed the most pronounced upregulation under hypoxic conditions. TLR9 protein expression was similarly induced by CoCl2 as well as in a 0.1% O2 atmosphere. Hypoxia increased the protein levels of γH2A.X, a marker for DNA damage and cellular senescence. The TLR9 agonist ODN 1826 induced the gene expression of downstream signaling molecules (MYD88, IRF7, RELA), inflammatory factors (IFNA, COX2), and MMP9 as well as the secretion of TGF-β1. These effects were reversed by TLR9 inhibitors (ODN 2088 and ODN INH-18). Transforming growth factor (TGF)-β1 significantly suppressed the TLR9 expression at both the mRNA and protein levels. This suppressive effect was reversed at the RNA level by inhibiting components of the TGF-β1 signaling pathway, including activin receptor-like kinase (ALK), Smad3, p38 mitogen-activated protein kinase (p38 MAPK), c-Jun N-terminal kinase (JNK), and phosphatidylinositol 3-kinase (PI3K) under hypoxic conditions.

CONCLUSIONS: TLR9 activation under hypoxic conditions initiates pro-inflammatory pathways in RPE cells. In the aging retina, viral and bacterial infections and/or DAMPs may further amplify these responses, worsening retinal degeneration. TGF-β1 may exert protective, anti-inflammatory effects by downregulating TLR9 expression.},
}

*Retinal Pigment Epithelium/metabolism/cytology/drug effects
Humans
*Toll-Like Receptor 9/genetics/metabolism/agonists
*Transforming Growth Factor beta1/metabolism/pharmacology
Apoptosis/drug effects
Cell Proliferation/drug effects
Cell Hypoxia/drug effects
Cobalt/pharmacology
*Epithelial Cells/metabolism/drug effects/cytology
Signal Transduction/drug effects
Cell Survival/drug effects
Gene Expression Regulation/drug effects
Cell Line
Toll-Like Receptor Agonists
Cellular Senescence/drug effects
RNA, Messenger/genetics/metabolism

@article {pmid42774060,
year = {2026},
author = {Dohl, J and Zaw, NL and Nguyen, J and Burns, G and Park, B and Atilano, S and Schneider, K and Chwa, M and Kenney, MC},
title = {Assessing mitochondrial phenotypes in a cybrid model of dry age-related macular degeneration.},
journal = {Molecular vision},
volume = {32},
number = {},
pages = {196-208},
pmid = {42774060},
issn = {1090-0535},
mesh = {Humans ; *Mitochondria/metabolism/pathology/genetics ; DNA, Mitochondrial/genetics/metabolism ; Phenotype ; Retinal Pigment Epithelium/metabolism/pathology ; *Geographic Atrophy/metabolism/pathology/genetics ; *Hybrid Cells/metabolism/pathology ; Membrane Potential, Mitochondrial ; Oxygen Consumption ; Cell Line ; Blood Platelets/metabolism/pathology ; Mitochondrial Proteins/metabolism/genetics ; Reactive Oxygen Species/metabolism ; *Macular Degeneration/metabolism/pathology/genetics ; },
abstract = {PURPOSE: Dry age-related macular degeneration (DAMD) is the leading cause of vision loss in developed countries, yet there are no FDA-approved treatments currently available. Mitochondria play a significant role in the pathology of DAMD; the retinal pigment epithelium cells of patients with DAMD exhibit mitochondrial dysfunction, elevated levels of mitochondrial DNA lesions, and increased mitochondrial reactive oxygen species. Investigations into the mitochondrial contributions to DAMD are complex as human tissue is challenging to acquire, and animal models do not fully recapitulate disease phenotypes. Cytoplasmic hybrid (cybrid) cells, formed by depleting the mitochondria of an immortalized cell line and fusing with patient platelets, are a possible model for mitochondrial studies on DAMD. This study evaluates if cybrid models of DAMD recapitulate the mitochondrial hallmarks of the disease, including mitochondrial dysfunction, decreased mitochondrial protein levels, lipid accumulation, and mitochondrial DNA lesions.

METHODS: The mitochondrial functions of five healthy and five DAMD cybrid cell lines were compared based on mitochondrial oxygen consumption rates, membrane potential, and protein expression. Secondary factors of mitochondrial dysfunction, including lipid accumulation and mitochondrial DNA stress response, were also examined.

RESULTS: Compared to healthy control cybrid lines, we found no alterations in bioenergetics, protein levels, and lipid accumulation in DAMD cybrid lines. Mitochondrial DNA stress responses were aberrant in DAMD cybrids compared to healthy controls, suggesting some conserved mitochondrial dysfunction.

CONCLUSIONS: Taken together, this study suggests that these DAMD cybrids do not fully recapitulate DAMD mitochondrial pathology, though this is limited to the study population of males with the H mtDNA haplogroup. However, there may be a niche for cybrid cell lines in investigating mitochondrial DNA phenotypes in patients with DAMD. This is likely because DAMD is a multifactorial disease, dependent upon an individual's genetics and the retinal microenvironment.},
}

Humans
*Mitochondria/metabolism/pathology/genetics
DNA, Mitochondrial/genetics/metabolism
Phenotype
Retinal Pigment Epithelium/metabolism/pathology
*Geographic Atrophy/metabolism/pathology/genetics
*Hybrid Cells/metabolism/pathology
Membrane Potential, Mitochondrial
Oxygen Consumption
Cell Line
Blood Platelets/metabolism/pathology
Mitochondrial Proteins/metabolism/genetics
Reactive Oxygen Species/metabolism
*Macular Degeneration/metabolism/pathology/genetics

@article {pmid42774544,
year = {2026},
author = {Crincoli, E and Borrelli, E and Savastano, MC and Catania, F and Carlà, MM and Bacherini, D and Caporossi, T and Scampoli, A and Giannuzzi, F and Rizzo, C and Vallino, V and Boscia, G and Savastano, A and Reibaldi, M and Rizzo, S},
title = {Differential Remodeling of the Macular Neovascular Network under Different Anti-VEGF Agents in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101336},
pmid = {42774544},
issn = {2666-9145},
abstract = {PURPOSE: To compare treatment-induced changes in OCT B-scan and OCT angiography (OCTA)-derived characteristics of the macular neovascular (MNV) network among different anti-VEGF agents in neovascular age-related macular degeneration (nAMD).

DESIGN: Multicenter retrospective observational cohort study.

SUBJECTS: A total of 120 eyes from 102 patients with nAMD treated with ranibizumab 0.5 mg every 4 weeks (n = 30), aflibercept 2.0 mg every 4 weeks (n = 30), aflibercept 8.0 mg every 12 weeks (n = 30), or faricimab 6.0 mg every 8 weeks (n = 30) in a treat-and-extend regimen.

METHODS: Eyes with good-quality OCT B-scan and OCTA acquisitions at baseline and 1-year follow-up were included. OCT B-scan variables included pigment epithelium detachment (PED) height, PED homogeneity, and presence of intraretinal cystoid lesions and hyperreflective foci. OCT angiography variables included greatest linear diameter (GLD), MNV area, vessel density (VD), vessel length density (VLD), and VD index (VDI).

MAIN OUTCOME MEASURES: Between-group differences in OCT B-scan and OCTA parameters at 1-year follow-up, adjusted for baseline values and clinical covariates using multivariable regression with cluster-robust standard errors.

RESULTS: Baseline characteristics were comparable across groups. Significant between-group differences were observed at 1 year for GLD (P = 0.003), MNV area (P = 0.001), VD (P < 0.001), VLD (P = 0.002), and VDI (P < 0.001). Faricimab-treated eyes consistently showed the lowest adjusted 1-year values for all OCTA endpoints, with a mean VDI of 1.150 ± 0.07 compared with 1.453 ± 0.05 for ranibizumab, 1.334 ± 0.06 for aflibercept 2 mg, and 1.231 ± 0.06 for aflibercept 8 mg. Structural OCT outcomes differed significantly for PED height (P = 0.001) and PED homogeneity (P = 0.007), with faricimab showing the lowest PED height and highest homogeneity. No significant differences were observed for qualitative variables.

CONCLUSIONS: Dual VEGF-A/angiopoietin-2 inhibition with faricimab induces greater anatomical remodeling of the MNV network compared with VEGF-A inhibition alone, with a distinct pattern characterized by preferential impact on larger-caliber vessels. These findings suggest that targeting the angiopoietin-2 pathway extends the morphological effects of anti-VEGF therapy beyond peripheral capillary pruning. Long-term studies are needed to determine whether deeper anatomical suppression translates into improved clinical outcomes or influences the trajectory of macular atrophy.

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

@article {pmid42775094,
year = {2026},
author = {Futterknecht, S and Pfau, M and Hall, U and Gabrani, C and Anders, P and Ansari, G and Traber, GL and Scholl, HP and Feltgen, N and Herzog, M and Garobbio, SA and Pfau, K},
title = {Spatial-Frequency-Dependent Contrast Sensitivity in Early and Intermediate Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101351},
pmid = {42775094},
issn = {2666-9145},
abstract = {OBJECTIVE: To evaluate spatial-frequency-dependent differences in contrast sensitivity across early and intermediate age-related macular degeneration (eAMD and iAMD) and explore the discriminative value of visual function metrics beyond age.

DESIGN: Cross-sectional observational study.

SUBJECTS: Ninety-six participants from the Multimodal Assessment of Visual Function in Intermediate AMD study, including 49 controls, 14 participants with eAMD, and 33 with iAMD.

METHODS: Contrast sensitivity was assessed using the quick contrast sensitivity function method at six spatial frequencies from 1 to 18 cycles per degree, with derivation of contrast acuity and area under the log contrast sensitivity function (AULCSF). Additional visual function measures included microperimetry mean sensitivity, best-corrected visual acuity, and low-luminance visual acuity. Linear mixed-effects models evaluated associations between AMD stage, spatial frequency, and contrast sensitivity after adjustment for age- and lens-related covariates. Secondary analyses assessed the discriminative performance of visual function metrics using receiver operating characteristic analyses.

MAIN OUTCOME MEASURES: Contrast sensitivity across spatial frequencies and discriminative performance of visual function metrics.

RESULTS: In age- and lens-adjusted mixed-effects models, contrast sensitivity differed significantly by AMD stage (P < 0.001), with a significant AMD stage × spatial frequency interaction (P = 0.035). Compared with controls, iAMD showed lower adjusted contrast sensitivity across most spatial frequencies, whereas eAMD differences were most pronounced at intermediate spatial frequencies. Discriminative analyses showed stronger separation of controls from iAMD than from eAMD. Microperimetry mean sensitivity provided the highest numerical discrimination for control versus iAMD and eAMD versus iAMD, whereas high-frequency contrast sensitivity and AULCSF performed best for control versus eAMD. Incremental gains beyond age- and lens-related covariates were modest for eAMD but larger for iAMD and for distinguishing eAMD from iAMD.

CONCLUSIONS: Contrast sensitivity differences in AMD are spatial-frequency-dependent and vary by disease stage after adjustment for age and lens-related covariates. Quick contrast sensitivity function-derived metrics showed modest incremental discrimination for eAMD, whereas microperimetry mean sensitivity and selected low-frequency contrast sensitivity measures better distinguished iAMD from controls and eAMD. These findings support spatial-frequency-resolved functional testing as an exploratory measure for AMD characterization; larger, age- and lens-balanced longitudinal cohorts are needed to determine prognostic utility.

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

@article {pmid42775100,
year = {2026},
author = {Basile, M and Valentini, I and Calosci, EM and Sciomenta, I and Di Brino, E and Rumi, F and Barca, F and De Angelis, L and Savastano, A and Francione, G and Sasso, P and Toro Mario, D and Giglio, R and Rizzo, S},
title = {Cost-Effectiveness of the Smaller-Incision New Generation Implantable Miniature Telescope for Late-Stage Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101357},
pmid = {42775100},
issn = {2666-9145},
abstract = {OBJECTIVE: To assess the cost-effectiveness of the smaller-incision new-generation implantable miniature telescope (SING IMT) versus conventional standard care (CSC) from the Italian National Health Service (NHS) and societal perspectives.

DESIGN: Model-based cost-utility analysis.

SUBJECTS: A simulated cohort of patients with bilateral late-/end-stage age-related macular degeneration (AMD), based on a prospective multicenter study population (mean age, 76 years) eligible for SING IMT, compared with a clinically comparable cohort receiving CSC.

METHODS: A cohort Markov model with quarterly cycles and a lifetime horizon evaluated monocular SING IMT implantation, structured 6-month postoperative low-vision rehabilitation, and scheduled ophthalmologic follow-up. Costs included device acquisition, surgery, rehabilitation, follow-up, wet AMD treatment and monitoring, visual impairment and blindness, and adverse-event management. Costs and outcomes were discounted at 3% annually. Deterministic and probabilistic sensitivity analyses assessed uncertainty.

MAIN OUTCOME MEASURES: Incremental costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-utility ratio, and net monetary benefit (NMB) at a €40,000/QALY willingness-to-pay threshold.

RESULTS: In the deterministic base case, SING IMT provided 1.59 additional LYs and 1.27 additional QALYs versus CSC. From the NHS perspective, its incremental cost was €21,760.60, yielding incremental cost-effectiveness ratios of €13,712.33 per LY and €17,137.15 per QALY gained; incremental NMB was €29,031.05. Including societal blindness-related costs, SING IMT reduced total per-patient costs (€35,446.33 vs €74,035.45; difference, -€38,589.12), primarily through lower lifetime blindness costs. Thus, from the combined NHS and societal perspective, SING IMT was dominant, with an incremental NMB of €89,380.77. Results were robust in sensitivity analyses; baseline age was the main source of variability, whereas surgical time, visit frequency, and unit costs had marginal effects.

CONCLUSIONS: For appropriately selected Italian patients with late-stage AMD, SING IMT is expected to be cost-effective versus CSC, providing clinically meaningful gains in quality-adjusted survival. It is cost-effective but not cost-saving from the NHS perspective alone and becomes dominant when societal costs are included, owing mainly to avoided blindness-related expenditure. Findings are specific to the Italian health care context.

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

@article {pmid42775202,
year = {2026},
author = {Chen, X and Ji, J and Yao, J and Chen, P and Zhang, J and Liu, L and Wen, X},
title = {The CD39-CD73-adenosine axis: a pivotal regulator of retinal homeostasis and diseases.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1893953},
pmid = {42775202},
issn = {2296-634X},
abstract = {Extracellular purinergic signaling, mediated by nucleotides such as adenosine triphosphate (ATP) and adenosine, is a critical regulator of retinal homeostasis. Within the retina, this signaling pathway is indispensable for maintaining physiological functions. Dysregulation of extracellular purine balance is a key driver of retinal pathophysiology, contributing to inflammation, pathological angiogenesis, and neurodegeneration in diseases like diabetic retinopathy (DR), age-related macular degeneration (AMD), glaucoma, and retinopathy of prematurity (ROP). The hydrolysis of extracellular ATP to adenosine, primarily orchestrated by the sequential actions of NTPDase1/ENTPD1 (CD39) and ecto-5'-nucleotidase/NT5E (CD73), represents a fundamental mechanism for calibrating purinergic signals and shifting the microenvironment from pro-inflammatory to anti-inflammatory and protective. CD39 and CD73 are pivotal enzymes in regulating retinal purinergic equilibrium. Despite their well-characterized roles in tumor biology and cerebral pathophysiology, the expression, physiological functions, and pathological implications of CD39/CD73 in the retina remain understudied and lack systematic synthesis. This review synthesizes current understanding of the roles of CD39 and CD73 in retinal physiology and pathology, with a focus on their implications in DR, AMD, glaucoma, and ROP. Critically, this review provides the first systematic integration of their layer-specific spatial compartmentalization, context-dependent functional duality, and emerging metabolic roles in photoreceptor homeostasis. We also discuss emerging therapeutic strategies that target this pathway, addressing the growing need for translational research to preserve vision.},
}

@article {pmid42763047,
year = {2026},
author = {Yang, L and Li, Z},
title = {A New Omics View of Retinal Aging: Cell-Type Vulnerability, Spatial Niches, and Disease Susceptibility.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111243},
doi = {10.1016/j.exer.2026.111243},
pmid = {42763047},
issn = {1096-0007},
abstract = {Classical accounts of retinal aging emphasize oxidative, mitochondrial, inflammatory, vascular, proteostatic, and retinal pigment epithelium (RPE)-centered mechanisms. Omics studies now confirm and refine this non-uniformity, showing that aging-associated signals vary by cell type, anatomical niche, molecular layer, and functional reserve. Direct evidence from single-cell and single-nucleus transcriptomics is strong for lineage- and subtype-specific aging programs in neural retina, RPE, glia, vascular cells, and choroidal immune populations. Spatial omics can generate and test localization hypotheses across anatomically defined foveolar/foveal, parafoveal, perifoveal, peripheral, vascular, glial, optic nerve head, and RPE-Bruch's membrane-choroid niches, but direct spatial-omics evidence for normal human retinal aging remains sparse. Proteomic, metabolic, lipidomic, epigenomic, and imaging mass spectrometry data help determine whether transcriptional aging states translate into altered protein turnover, metabolic reserve, lipid handling, chromatin state, and inflammatory memory. AI-derived retinal age clocks provide population-scale imaging phenotypes, but color fundus photography alone is poorly depth-resolved; biological interpretation requires optical coherence tomography (OCT), visual function, biomarkers, destructive cell-type-resolved or spatially resolved tissue data, and longitudinal imaging or functional data. We integrate these findings into a multi-scale model in which normal retinal aging may lower resilience thresholds in defined cells and niches, thereby contributing to susceptibility to age-related macular degeneration, glaucoma, diabetic retinopathy, and inherited retinal degeneration. We also outline minimum standards for retinal aging omics, including anatomically specified sampling, donor metadata, evidence-source class interpretation, spatial validation, perturbation or rescue testing, and measurable endpoints of retinal resilience and visual function.},
}

@article {pmid42763542,
year = {2026},
author = {Aljied, R and Saggu, S and Chaudhary, V and Pigeyre, M and Griffith, LE and Raina, P},
title = {Multivariable Prognostic Models for Age-Related Macular Degeneration: A Systematic Review.},
journal = {Journal of ophthalmology},
volume = {2026},
number = {},
pages = {9231744},
pmid = {42763542},
issn = {2090-004X},
abstract = {BACKGROUND: Prognostic prediction models for age-related macular degeneration (AMD) are proliferating, driven by machine learning applied to retinal imaging. Although the methodological limitations of clinical prediction models are well recognized in general, AMD-specific multivariable prognostic models, as distinct from diagnostic or image-classification models, have not been appraised against contemporary prediction-model standards, with integrated assessment of outcome definitions, prediction horizons, calibration, validation design, and risk of bias.

OBJECTIVE: To systematically identify and critically appraise multivariable prognostic models predicting progression from non-late to late AMD and to determine whether quantitative synthesis was appropriate, with emphasis on model design, predictors, performance reporting, validation, and risk of bias.

METHODS: We searched PubMed/MEDLINE, and Embase from inception to April 2022, updated to December 2024, for studies developing, validating, or evaluating multivariable prognostic models for progression to late AMD. We extracted study population, outcomes, prediction horizons, predictors, modeling methods, performance measures, and validation approach and assessed risk of bias with PROBAST. Given substantial heterogeneity, findings were synthesized narratively in accordance with a prespecified conditional analysis plan (PROSPERO CRD42022323522).

RESULTS: Twenty studies were included. Models were derived from a small number of recurring cohorts, notably AREDS and HARBOR, of predominantly European ancestry; this limited population diversity was one of several constraints, alongside heterogeneous outcome definitions, infrequent calibration, and uncommon external validation. Approaches ranged from regression-based risk scores to deep learning applied to fundus photography, optical coherence tomography, or multimodal data. Because outcome definitions varied (composite late AMD, neovascular or exudative conversion, geographic atrophy or other atrophic endpoints, and treatment-initiation proxies), the observed AUC/c-statistic range (∼0.65-0.97) reflects differing prediction tasks rather than directly comparable performance. Calibration was addressed in six studies (30%), and fewer still met our definition of quantitative calibration. Imaging features and age were the most consistently retained predictors, and measures beyond discrimination were rare. Overfitting could not be excluded in several studies, as event counts, candidate-predictor numbers, use of shrinkage, and internal-validation procedures were incompletely reported. Ten of 20 studies were at low overall risk of bias, but calibration and external validation were uncommon across the evidence base as a whole.

CONCLUSIONS: Prognostic models for AMD progression are methodologically diverse but are drawn from few, homogeneous cohorts, with limited calibration and external validation, features that constrain interpretation of reported performance and transportability to routine, more diverse practice. Progress will depend less on new algorithms than on staged, feasible validation: prespecified outcomes and horizons, robust internal validation, routine calibration, and temporal or geographic validation with recalibration before clinical use. Until then, existing models should be regarded as exploratory rather than clinically actionable.},
}

@article {pmid42763736,
year = {2026},
author = {Chakraborty, D and Sinha, TK and Biswas, RK and Maiti, A and Barman, MJ and Bhattacharya, R and Boral, S and Das, A},
title = {Real-World Analysis of Switching Between Ranibizumab Biosimilars: Safety and Results - a Multicenter Retrospective Observational Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {624886},
pmid = {42763736},
issn = {1177-5467},
abstract = {PURPOSE: To describe disease-specific visual, anatomical, treatment-exposure, and documented safety outcomes over 24 weeks among eyes undergoing availability-driven switching between ranibizumab biosimilars in routine retinal practice in India.

METHODS: This multicenter retrospective observational cohort study reviewed records from January to December 2024. Baseline was the index-switch visit, before administration of the substituted ranibizumab biosimilar. Only one eye per patient was included; when both eyes were eligible, the right eye was selected by convention. Eligible eyes had at least one documented availability-driven biosimilar-to-biosimilar switch and complete 24-week follow-up. Outcomes were summarized descriptively because there was no non-switch comparator group.

RESULTS: Of 742 screened eyes, 595 eyes from 595 patients met the inclusion criteria and received 1625 intravitreal ranibizumab biosimilar injections over 24 weeks (mean, 2.73 injections per eye). One switch was recorded in 466 eyes (78.3%) and two switches in 129 eyes (21.7%). Mean BCVA improved from 0.57 logMAR at baseline to 0.26 at 12 weeks and 0.32 at 24 weeks; the early visual improvement therefore attenuated modestly by week 24 but remained better than baseline. Mean central macular thickness decreased from 490.4 micrometers at baseline to 273.6 micrometers at 24 weeks. At final follow-up, 369 eyes (62.0%) gained at least two lines and 488 eyes (82.0%) maintained or improved vision. No endophthalmitis, retinal detachment, or treatment-related systemic adverse event was documented in the available clinical records.

CONCLUSION: Eyes exposed to availability-driven switching between ranibizumab biosimilars showed favorable short-term visual and anatomical outcomes over 24 weeks. Because this retrospective study lacked a non-switch comparator and protocol-mandated safety or immunogenicity surveillance, it cannot establish an effect attributable to switching, comparative safety, equivalence, or formal interchangeability.},
}

@article {pmid42765048,
year = {2026},
author = {Kang, MJ and LaBarre, N and Karo, M and Soong, R and Vida, TA},
title = {Illuminating Risk: An Ecological Analysis of Artificial Light at Night and Childhood Myopia Using State-Level US Data.},
journal = {Risk management and healthcare policy},
volume = {19},
number = {},
pages = {628850},
pmid = {42765048},
issn = {1179-1594},
abstract = {PURPOSE: Childhood myopia is a growing global health concern, associated with serious vision complications later in life, including retinal detachment and myopic macular degeneration. While behavioral factors such as screen time and reduced outdoor exposure have been studied, the potential contribution of environmental light pollution, particularly artificial light at night (ALAN), remains underexplored at the population level.

METHODS: We analyzed 2019 data from 46 US states to examine the association between ALAN and the prevalence of childhood myopia (ages 0-17). VIIRS satellite-derived nighttime radiance was used as a proxy for outdoor ambient lighting. Using generalized additive modeling (GAM), we examined nonlinear associations while adjusting for behavioral (screen time, insufficient sleep) and structural (Medicaid coverage, uninsured children, vision screening, optometrist density, urbanization) factors. Multicollinearity was assessed using Spearman correlation and variance inflation factors.

RESULTS: The final GAM explained 65.3% of the deviance in childhood myopia prevalence (adjusted R[2] = 0.509). Higher ALAN was significantly associated with higher myopia prevalence (F = 8.39, p = 0.0068). Screen time showed a nonlinear relationship, whereas sleep deprivation showed an unexpected inverse association, potentially reflecting detection disparities. Medicaid coverage showed a U-shaped association, with both low and high coverage associated with higher prevalence. Vision screening rates were positively associated with myopia prevalence, likely reflecting improved detection. Urbanization, optometrist density, and the number of Asian children were not statistically significant.

CONCLUSION: ALAN is a population-level correlate of childhood myopia in the US. Although not indicative of individual-level risk, its association warrants further ecological investigation and may merit consideration in environmental health and urban planning discussions. These findings highlight the multifactorial nature of pediatric refractive error and the value of integrating environmental exposure data into public health vision surveillance. Further individual-level research is needed to assess causal mechanisms.},
}

@article {pmid42765882,
year = {2026},
author = {Tsukui, L and Miyata, M and Hata, M and Ooto, S and Tamura, H and Otsuka, A and Shirakami, M and Ueda-Arakawa, N and Miyake, M and Takahashi, A and Kadomoto, S and Muraoka, Y and Tsujikawa, A},
title = {ACUTE NEUROSENSORY RETINAL THINNING AND SHORT-TERM VISUAL OUTCOMES IN MASSIVE SUBMACULAR HEMORRHAGE: A LONGITUDINAL ANALYSIS FROM PRE-ONSET TO POST-DISPLACEMENT WITH SUBRETINAL TISSUE PLASMINOGEN ACTIVATOR.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000005014},
pmid = {42765882},
issn = {1539-2864},
abstract = {PURPOSE: To investigate longitudinal visual and structural changes from pre-onset to 1 month postoperatively in eyes with massive submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (nAMD) treated with subretinal tissue plasminogen activator (tPA) injection and to identify prognostic factors for visual outcomes.

METHODS: This retrospective observational study reviewed the medical records of consecutive eyes with massive SMH secondary to nAMD treated with pars plana vitrectomy with subretinal tPA injection and pneumatic displacement. We assessed best-corrected visual acuity (BCVA) and foveal sensory retinal thickness (FSRT) at pre-onset, preoperative, and 1-month postoperative time points.

RESULTS: Among 74 consecutive eyes treated with subretinal tPA injection for massive SMH, we analyzed 20 eyes with available pre-onset data. FSRT decreased significantly from 193.5 ± 101.4 μm at pre-onset to 107.0 ± 59.0 μm at 1 month postoperatively (P < 0.001). BCVA change negatively correlated with FSRT change (r = -0.56, P = 0.01). Univariable analysis showed that pre-onset BCVA significantly correlated with 1-month BCVA (r = 0.45, P = 0.049). At pre-onset, persistent fluid and pigment epithelial detachment were present in 65% and 15%, respectively.

CONCLUSIONS: Massive SMH causes acute and profound neurosensory retinal thinning, and pre-onset neuronal integrity may be a key determinant of visual outcomes. Because surgery cannot reverse this immediate damage, preventing hemorrhage by maintaining a strictly fluid-free macula may be an important proactive strategy.},
}

@article {pmid42767442,
year = {2026},
author = {Luthert, PJ and Faes, L and Foss, AJ and Fu, DJ and Hill, LJ and Huang, R and Kiel, C and Lee, WH and Matei, and Mirams, GR and Misson, G and Montesano, G and Niederer, S and Paraoan, L and Roberts, PA and Sivaprasad, S and Whitmore, SS and Zouache, MA and , and Bloomfield, PS},
title = {The Virtual Eye: An Integrative Multiscale Framework for Mechanistic Modelling of Ocular Physiology and Disease.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101529},
doi = {10.1016/j.preteyeres.2026.101529},
pmid = {42767442},
issn = {1873-1635},
abstract = {The Virtual Eye initiative described here seeks to build a versatile and integrative in silico platform, 'The Virtual Eye' that can capture and simulate the biology, physiology and function of the human eye, from molecular interactions to organ-level behaviour, in both healthy and diseased states. This effort has the potential to substantially deepen our understanding of the visual process, clarify the mechanistic basis of ocular diseases across multiple spatial and temporal scales, and support the development of therapeutic strategies for both common and rare eye conditions. A coordinated undertaking among biologists, biophysicists, clinicians, mathematicians and engineers has led to the development of a shared roadmap and collaborative investigations into foundational challenges, including for instance retinal vascular flow and the progression of geographic atrophy lesions in age-related macular degeneration (AMD). Here, we present an initial framework for advancing the Virtual Eye and define core models required to ensure its coherent development and expansion. This framework is rooted in current knowledge of biological mechanisms and integrated with mathematical representation, with the initial ambition of simulating a defined period of healthy function using a range of stimuli and experiments representing the natural world. We identify nine core modelling tasks that capture the healthy physiology of the eye and outline seven disease processes representing perturbations of normal function. Together, these components could form the first iteration of the Virtual Eye conceptual framework and roadmap for building it, enabling controlled experimental manipulation of a simulated system designed to generate realistic and biologically meaningful behaviours.},
}

@article {pmid42767615,
year = {2026},
author = {Balas, M and Mihalache, A and Jhaveri, A and Kaleem, S and Popovic, MM and Kertes, PJ and Muni, RH},
title = {Congestive heart failure and other cardiac adverse events after intravitreal anti-VEGF therapy: a systematic review and meta-analysis.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2026.08.033},
pmid = {42767615},
issn = {1715-3360},
abstract = {OBJECTIVE: To evaluate congestive heart failure (CHF) and other cardiac adverse events (AEs) after intravitreal anti-vascular endothelial growth factor (VEGF) therapy for retinal vascular disease and compare risks across agents.

DESIGN: A systematic review and meta-analysis.

METHODS: Registered review (PROSPERO CRD42022302658) searched Ovid MEDLINE, Embase, and the Cochrane Library from January 2005 to February 2024 for randomized controlled trials (RCTs) of intravitreal anti-VEGF therapy for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion. Eligible trials compared an anti-VEGF agent with sham or another anti-VEGF agent and reported CHF (primary outcome) or other cardiac AEs (secondary outcomes: arrhythmias, heart failure/cardiomyopathy, inflammatory heart disease, ischemic heart disease, or valvular heart disease). Risk of bias was assessed with RoB 2, certainty with GRADE, and random-effects models generated risk ratios (RRs) with 95% confidence intervals (CIs).

RESULTS: Fourteen reports describing 20 trials (11,803 eyes; mean age 71 ± 12 years; 53% female) were included. CHF was uncommon overall: aflibercept 2.0% (84/4172), ranibizumab 2.2% (25/1158), faricimab 2.3% (44/1926), brolucizumab 2.5% (40/1612), and sham 3.8% (20/524). Ranibizumab did not differ from sham for CHF (RR = 1.53, 95% CI 0.46-5.06), whereas aflibercept was associated with higher CHF risk versus sham in 2 trials (RR = 2.08, 95% CI: 1.03-4.23). No significant CHF differences were detected between aflibercept and brolucizumab, faricimab, or ranibizumab. Other cardiac events were similar across agents.

CONCLUSIONS: CHF and other AEs after intravitreal anti-VEGF therapy were uncommon in RCTs and comparable across agents. The aflibercept-sham CHF signal was based on limited evidence and should be interpreted cautiously.},
}

@article {pmid42767752,
year = {2026},
author = {Miao, H and Tang, L and Lyu, X and Wu, L},
title = {Treatment burden and adherence in adults receiving long-term anti-VEGF intravitreal injections for retinal disease: a qualitative evidence synthesis protocol.},
journal = {BMJ open},
volume = {16},
number = {9},
pages = {e125908},
doi = {10.1136/bmjopen-2026-125908},
pmid = {42767752},
issn = {2044-6055},
mesh = {Humans ; Intravitreal Injections ; Systematic Reviews as Topic ; Qualitative Research ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Research Design ; *Retinal Diseases/drug therapy ; Macular Degeneration/drug therapy ; *Medication Adherence/psychology ; Cost of Illness ; Adult ; },
abstract = {INTRODUCTION: Retinal diseases such as neovascular age-related macular degeneration and diabetic macular oedema are leading causes of irreversible vision loss and require intravitreal anti-vascular endothelial growth factor (VEGF) injections over many years. Repeated treatment imposes physical, psychological, social and financial burdens and is associated with reduced adherence and poorer real-world outcomes. Existing research is largely quantitative and does not explain, from patients' perspectives, why people persist with, struggle against or discontinue burdensome treatment. This review will identify, appraise and synthesise qualitative studies to understand the burden of long-term anti-VEGF therapy, how it shapes adherence and the implications for patient-centred nursing care, shared decision-making and injection-service design.

METHODS AND ANALYSIS: This protocol is reported in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P); the completed synthesis will be reported following Enhancing Transparency in Reporting the Synthesis of Qualitative Research. We will use Thomas and Harden's three-stage thematic synthesis and the Population, Phenomenon of Interest, Context and Study design framework. Eligible studies are primary qualitative studies and independently extractable qualitative components of mixed-methods studies involving adults (≥18 years) receiving long-term anti-VEGF therapy for retinal disease, irrespective of publication language. Initial searches of nine databases (PubMed, Embase, CINAHL, PsycINFO, Web of Science, Scopus, CNKI, Wanfang Data and SinoMed) were conducted from inception between 31 May and 2 June 2026 and will be updated before completion of the review. Citation tracking and thesis-repository searches will supplement the database searches. Two reviewers will independently screen records, extract data and appraise quality using the Joanna Briggs Institute checklist, with disagreements resolved by a third reviewer. Confidence in each finding will be assessed using Grading of Recommendations Assessment, Development and Evaluation-Confidence in the Evidence from Reviews of Qualitative research.

ETHICS AND DISSEMINATION: Ethical approval is not required because the review uses published data. Six to eight patients, with up to two family advisers, will help interpret preliminary themes and develop a plain-language summary. Findings will be disseminated through peer-reviewed publication and conference presentation.

PROSPERO REGISTRATION NUMBER: CRD420261405614.},
}

Humans
Intravitreal Injections
Systematic Reviews as Topic
Qualitative Research
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
Research Design
*Retinal Diseases/drug therapy
Macular Degeneration/drug therapy
*Medication Adherence/psychology
Cost of Illness
Adult

@article {pmid42768077,
year = {2026},
author = {Bilbao-Malavé, V and de la Puente, M and Ochoa-Tejada, L and Irigoyen Bañegil, C and Anduaga-Beramendi, A and Fraga de la Viesca, M and Llorente-González, S and Sáenz de Viteri, M and Hernández, M and Heras-Mulero, H and Arias-Barquet, L and García-Layana, A and Recalde, S and González-Zamora, J},
title = {Association between choroidal structure and retinal fluid location in type 1 neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42768077},
issn = {1476-5454},
abstract = {OBJECTIVES: To correlate choroidal structure parameters with the presence and amount of subretinal fluid (SRF) and intraretinal fluid (IRF) in treatment-naïve neovascular age-related macular degeneration (nAMD) patients with type 1 macular neovascularisation (MNV).

METHODS: A retrospective study reviewed clinical records of 96 patients diagnosed with nAMD between 2015 and 2022. Optical coherence tomography (OCT) scans were analysed for choroidal thickness, choroidal vascularity index (CVI), and large choroidal vessel index (LCVI) using ImageJ software with automated binarisation. SRF was manually quantified using embedded OCT tools, and IRF volume was measured using an artificial intelligence-based platform. Patients with type 1 MNV (n = 56) were included for fluid-choroidal correlations. Statistical analyses included t-tests, Mann-Whitney U tests, and Spearman correlations (p < 0.05).

RESULTS: In type 1 MNV eyes, SRF presence was associated with greater choroidal thickness (p = 0.03), and SRF area correlated positively with choroidal thickness (p = 0.02) and foveal LCVI (p = 0.004). Maximum SRF height correlated with foveal LCVI (p = 0.007). IRF presence was linked to reduced choroidal thickness (p = 0.0008), and IRF volume inversely correlated with choroidal thickness (p = 0.01) and macular LCVI (p = 0.002). No significant choroidal changes were observed pre-MNV or compared to fellow eyes.

CONCLUSIONS: In treatment-naïve type 1 MNV, choroidal thickness and LCVI exhibit opposite associations with subretinal and intraretinal fluid, emphasising distinct pathophysiological mechanisms: choroidal venous overload may be associated with SRF accumulation, while choroidal thinning may be implicated in IRF formation. These findings may help generate hypothesis regarding variability in anti-VEGF treatment response and suggest that choroidal characteristics warrant further investigation as potential biomarkers for future individualised management strategies.},
}

@article {pmid42768326,
year = {2026},
author = {Karasu, B and Yılmaz Tuğan, B and Kesim, E and Özen, S},
title = {Rapid choroidal neovascularization after non-flap internal limiting membrane peeling for macular hole in a patient with AMD: a case report and literature review.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42768326},
issn = {1471-2415},
mesh = {Humans ; *Retinal Perforations/surgery/diagnosis/complications ; Female ; Aged ; *Choroidal Neovascularization/etiology/diagnosis ; *Vitrectomy/adverse effects ; Visual Acuity ; Tomography, Optical Coherence ; *Macular Degeneration/complications ; *Basement Membrane/surgery ; *Epiretinal Membrane/surgery ; *Postoperative Complications ; Fluorescein Angiography ; },
abstract = {BACKGROUND: Choroidal neovascularization (CNV) following macular hole (MH) surgery is a rare complication. While the exact pathogenesis remains unclear, previous reports in the literature suggest that it can occur in patients with pre-existing age-related macular degeneration (AMD) or macular drusen. In this report, we present a case that highlights the potential biomechanical triggers of this complication in an eye with AMD.

CASE PRESENTATION: We report the case of a 70-year-old female patient with AMD who presented with a full-thickness macular hole (FTMH). She underwent an uncomplicated 25-gauge pars plana vitrectomy with brilliant blue G-assisted internal limiting membrane (ILM) peeling and perfluoropropane gas tamponade. Notably, the ILM flap technique was not utilized; only standard, non-flap peeling without intraoperative complications was performed. Just 6 weeks postoperatively, the patient experienced a sudden decline in visual acuity due to the rapid development of CNV at the border of the ILM peeled-off area. Intravitreal aflibercept treatment was subsequently planned.

CONCLUSIONS: This case suggests that, in eyes with underlying AMD, CNV may develop rapidly after standard ILM peeling even without an ILM flap technique. Biomechanical stress related to ILM removal, potentially involving macular displacement and mechanical stress on Müller cells, may be a possible contributing factor, but causality cannot be established from a single case. Physicians should maintain high vigilance for this vision-threatening complication during the early postoperative period after MH surgery.},
}

Humans
*Retinal Perforations/surgery/diagnosis/complications
Female
Aged
*Choroidal Neovascularization/etiology/diagnosis
*Vitrectomy/adverse effects
Visual Acuity
Tomography, Optical Coherence
*Macular Degeneration/complications
*Basement Membrane/surgery
*Epiretinal Membrane/surgery
*Postoperative Complications
Fluorescein Angiography

@article {pmid42757636,
year = {2026},
author = {Goodrich, Z and Schneider, J},
title = {Zinc-associated Copper Deficiency Myelopathy: A Case Report.},
journal = {Clinical neuropharmacology},
volume = {},
number = {},
pages = {},
doi = {10.1097/WNF.0000000000000701},
pmid = {42757636},
issn = {1537-162X},
abstract = {OBJECTIVE: Copper deficiency myelopathy is an uncommon but potentially reversible neurologic disorder characterized by sensory ataxia, gait impairment, and dorsal column dysfunction. Acquired copper deficiency most commonly results from malabsorption, prior gastrointestinal surgery, or excess zinc exposure. Zinc induces intestinal metallothionein, which preferentially binds copper and reduces its systemic absorption, potentially leading to hypocupremia and neurologic dysfunction. Although zinc-containing nutritional supplements are widely used, clinically significant neurologic complications remain rare.

METHODS: A retrospective review of the patient's medical history was performed in addition to a comprehensive literature review.

RESULTS: A 70-year-old woman receiving long-term zinc-containing PreserVision AREDS 2 supplementation for age-related macular degeneration presented with 6 months of progressive paresthesia, gait instability, and frequent falls. Neurologic examination demonstrated bilateral sensory deficits and weakness, while magnetic resonance imaging revealed dorsal column T2 hyperintensity. Laboratory evaluation showed undetectable serum copper, mildly elevated serum zinc, normocytic anemia, hypokalemia, and concurrent thiamine deficiency. Zinc-containing supplementation was discontinued, and the patient received copper and thiamine replacement. Over the following two months, serum copper normalized, and she experienced substantial neurologic recovery with restoration of independent ambulation.

CONCLUSIONS: This report describes a case of copper deficiency myelopathy in a patient receiving long-term high-dose zinc supplementation in the setting of multiple nutritional abnormalities. It highlights the importance of including copper deficiency in the differential diagnosis of patients receiving zinc-containing supplements who present with progressive myelopathy. It is intended to be hypothesis-generating and suggests that individual susceptibility and concurrent nutritional factors may contribute to the development of zinc-associated copper deficiency.},
}

@article {pmid42757924,
year = {2026},
author = {Borchert, GA and Ferreira, LAF and Raji, S and Yu, J and Segovia, M and MacLaren, RE and Downes, SM and Cehajic-Kapetanovic, J and Xue, K and De Silva, SR},
title = {Apolipoprotein E2/2 (APOE2/2) Genotype Is Associated With Reduced Choroidal Thickness.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {11},
pages = {38},
doi = {10.1167/iovs.67.11.38},
pmid = {42757924},
issn = {1552-5783},
mesh = {Humans ; Female ; *Apolipoprotein E2/genetics ; Male ; Genotype ; Middle Aged ; *Choroid/pathology ; Tomography, Optical Coherence/methods ; Prospective Studies ; *Macular Degeneration/genetics ; Visual Acuity/physiology ; Aged ; Apolipoprotein E3/genetics ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a leading cause of visual impairment in individuals >50 years. The APOE2 allele has been associated with increased AMD risk compared to the common APOE3 allele. However, the retinal phenotype of APOE2/2 individuals has not been characterized. This study aimed to compare the macular structure and function of APOE2/2 versus APOE3/3 homozygous individuals.

METHODS: Age- and sex-matched participants with APOE2/2 and APOE3/3 genotypes were prospectively recruited from the Oxford Biobank. Phenotyping included best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), microperimetry, refractive error, multimodal retinal imaging, fasting lipid profile, and EPIC-Norfolk food frequency questionnaires. A linear mixed model of paired eye measurements with a subject-specific random intercept was applied, including age, sex, smoking status and refractive error as covariates. Findings were compared to similar UK Biobank cohorts.

RESULTS: 24 participants were recruited: 12 APOE2/2 and 12 APOE3/3 (mean age 60.5 ± 5.7 (standard deviation) years, female/male 1:1; 87.5% non-smokers). Serum triglycerides were significantly higher in APOE2/2 participants (1.8 vs. 1.03 mM, P = 0.010). A novel finding of reduced choroidal thickness was found in APOE2/2 compared to APOE3/3 participants after multivariate analysis controlling for age, sex, smoking status and refractive error (estimated difference 57.8 µm, P = 0.02). Optical coherence tomography segmentation showed a trend toward reduced retinal thickness in APOE2/2 compared to APOE3/3 participants, but did not reach statistical significance. No differences in BCVA, LLVA, or retinal sensitivity were detected. Diet and background AMD genetic risk were comparable.

CONCLUSIONS: We report a novel genotype-phenotype association of reduced choroidal thickness in individuals homozygous for APOE2/2 compared with normative APOE3/3 controls.},
}

Humans
Female
*Apolipoprotein E2/genetics
Male
Genotype
Middle Aged
*Choroid/pathology
Tomography, Optical Coherence/methods
Prospective Studies
*Macular Degeneration/genetics
Visual Acuity/physiology
Aged
Apolipoprotein E3/genetics

@article {pmid42759221,
year = {2026},
author = {Neau, J and Turpin, A and Rajendrabose, D and Haneef, R and Soltani, O and Dilange, L and Couasnard, A and Bodaghi, B and Baudouin, C and Tubach, F and Guillo, S and Dechartres, A},
title = {Algorithms for the identification of ophthalmic diseases in medico-administrative databases: A systematic review.},
journal = {Journal of epidemiology and population health},
volume = {74},
number = {5},
pages = {203788},
doi = {10.1016/j.jeph.2026.203788},
pmid = {42759221},
issn = {2950-4333},
abstract = {CONTEXT: Medico-administrative databases (MADs) are increasingly used in comparative effectiveness research.

OBJECTIVE: To conduct a systematic review of algorithms used for the identification of key ophthalmic diseases in MADs: age-related macular degeneration (AMD), diabetic retinopathy (DR)/ diabetic macular edema (DME), glaucoma, cataract and uveitis.

METHODS: We searched PubMed between June 30, 2016, and August 6, 2024, using keywords related to MADs and the ophthalmic diseases of interest. Two reviewers independently selected studies and extracted data.

RESULTS: From the 1719 references identified, 315 were selected describing a total of 523 algorithms. Approximately half of the study objectives were related to the identification of factors associated with the onset of ophthalmic diseases, exacerbation, or hospitalization (48%, n = 151). Only 2% (n = 6) focused exclusively on the development and/or validation of algorithms. Most studies were from Taiwan (36%, n = 113), Korea (27%, n = 84) and the United States (20%, n = 64). From the 523 algorithms, a validation was mentioned for 47 (9%). After regrouping close algorithms, 433 different algorithms were identified concerning glaucoma (34%, n = 146), DR/DME (26%, n = 114), AMD (18%, n = 80), cataract (11%, n = 47) and uveitis (11%, n = 46). About half of these algorithms used diagnosis codes only (58%, n = 251), while others combined diagnosis codes and procedures (16%, n = 69), or diagnosis codes and drugs (12%, n = 50).

CONCLUSION: This systematic review showed heterogeneity between algorithms used to identify the same pathology, raising the question of which ones are more appropriate to use in a particular context. Moreover, most algorithms were not validated despite the potential impact on study results.},
}

@article {pmid42759378,
year = {2026},
author = {Piloni-Parreira, R and Barbosa, MS and Neves, LL and Santana, HL and Rodrigues, JMRDS and Tavares, RS and Isaac, DLC and Pereira de Ávila, M},
title = {Ophthalmological and epidemiological profiles of Brazilian patients with philadelphia-negative Myeloproliferative neoplasms.},
journal = {Hematology, transfusion and cell therapy},
volume = {48},
number = {4},
pages = {106536},
doi = {10.1016/j.htct.2026.106536},
pmid = {42759378},
issn = {2531-1387},
abstract = {INTRODUCTION: Philadelphia-negative myeloproliferative neoplasms comprise a rare and biologically heterogeneous spectrum of hematopoietic stem cell malignancies. According to established clinicopathological criteria, these entities are principally categorized as polycythemia vera, essential thrombocythemia, or primary myelofibrosis. Ophthalmic manifestations are common in hematological diseases, yet they remain under-researched in this patient population.

METHODS: The purpose of this study is to analyze the ophthalmological and epidemiological profile of patients, describing ocular findings of Philadelphia-negative Myeloproliferative Neoplasms. Twenty-one individuals (forty-two eyes) with a Philadelphia-negative myeloproliferative neoplasm had their medical records selected, analyzed and relevant data collected. They were subsequently subjected to a complete ophthalmological evaluation, with assessment of visual acuity, biomicroscopy and fundoscopy employing wide-field color retinography and wide-field fundus autofluorescence examinations.

RESULTS: The mean age of participants was approximately 60 years, with a white demographic predominance and no sex bias. Most patients achieved early clinical diagnosis and effective disease control, with a high frequency harboring the JAK2 V617F mutation. Patients reported no subjective complaints of low visual acuity, and posterior segment involvement was sparse. Retinal hemorrhages were uncommon, occurring predominantly in polycythemia vera due to hyperviscosity or microvascular thrombosis in the absence of confounding ocular or systemic conditions. Fundoscopic lesions were mostly driven by comorbid diagnoses, specifically age-related macular degeneration (19.4%) and hypertensive retinopathy (9.5%).

CONCLUSION: Brazilian patients with well-controlled Ph-NMPs and early diagnosis rarely exhibit primary retinal complications or subjective low visual acuity. Retinal manifestations, particularly hemorrhages, are infrequent despite high rates of the JAK2 V617F mutation. Ocular findings in this population are more commonly driven by concurrent systemic or degenerative conditions, notably age-related macular degeneration.},
}

@article {pmid42759656,
year = {2026},
author = {Jeong, YD and Jeon, S and Shin, W and Park, S and Park, T and Kim, TH and Smith, L and Rahmati, M and Yang, JM and Yon, DK},
title = {Global burden of age-related macular degeneration, with forecast up to 2050: a modelling study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.09.019},
pmid = {42759656},
issn = {2468-6530},
abstract = {TOPIC: We aimed to estimate the prevalence of age-related macular degeneration (AMD) using a single standardized classification and provide comparable global, regional, and national burden estimates from 1990 to 2050.

CLINICAL RELEVANCE: Owing to the marked heterogeneity in AMD classification criteria across the included studies, there remains a need to delineate the burden of AMD using a unified and standardized classification system.

METHODS: Following registration (CRD420251067039), a search was conducted in PubMed/MEDLINE, Embase, CINAHL, and Google Scholar. Eligible epidemiological studies reporting AMD prevalence were included, and extracted prevalence data were harmonized according to the Beckman classification. An expectation-maximization algorithm was applied to disaggregate data into early, intermediate, geographic atrophy (GA), and neovascular AMD (nAMD). Prevalence was modeled for 204 countries and territories using DisMod-MR, with projections to 2050 using a hybrid machine learning approach, including scenario analyses of tobacco reduction and increased physical activity. Estimates were stratified by clinical stage and ethnicity with 95% uncertainty intervals (UIs). Prevalence of AMD stratified by clinical stage (early, intermediate, geographic atrophy [GA], and neovascular AMD [nAMD]), age, sex, and ethnicity across 204 countries from 1990 to 2021, with projections and risk-reduction scenarios through 2050.

RESULTS: In 2021, the global prevalence of AMD across all stages was 10.03% (95% UI, 8.30-12.06); early AMD, 5.40% (4.72-6.14); intermediate AMD, 4.01% (3.41-4.66); GA, 0.32% (0.26-0.39); and nAMD, 0.31% (0.26-0.36). Prevalence increased from 1990 to 2021, whereas age-standardized rates declined. AMD prevalence rose sharply with age, with no significant sex differences in early or intermediate AMD. GA prevalence was highest among Hispanic populations, and nAMD among European populations. Projections indicate continued increases through 2050, with reductions under tobacco reduction and increased physical activity scenarios.

CONCLUSIONS: This study provides the first global, regional, and national prevalence estimates of AMD stratified by the Beckman classification, offering evidence to inform clinical practice and health policy.},
}

@article {pmid42755766,
year = {2026},
author = {Guo, W and Wan, J and Zhang, F and Wu, X and Hong, Y and Wang, Z and Bian, W},
title = {Effect of a mobile application-based whole-course nutrition management intervention in patients with age-related macular degeneration: a randomized controlled trial.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1855870},
pmid = {42755766},
issn = {2296-2565},
mesh = {Humans ; *Macular Degeneration/diet therapy ; Female ; Male ; Aged ; *Mobile Applications ; Quality of Life ; Aged, 80 and over ; Nutritional Status ; Middle Aged ; Visual Acuity ; *Nutrition Therapy/methods ; },
abstract = {AIMS AND OBJECTIVES: Evaluate the effect of the application (APP)-based AIM-AMD (Assessment, Introduction, Management, and App-based Maintenance Dynamically) nutrition management model in patients with age-related macular degeneration (AMD).

BACKGROUND: Nutritional intervention are one of the only ways to prevent the development of AMD and slow its progression. However, poor compliance with patient nutritional management leads to ineffective nutritional supplementation outcomes.

DESIGN: A randomised controlled trial was conducted from October 2023-January 2024 and performed according to the CONSORT guidelines.

METHODS: A total of 140 participants were randomly assigned to the intervention or control group. The intervention was administered three times per week for a period of 3 months. The intervention group was adopted with APP-based AIM-AMD nutrition management + routine nursing, while the control group was adopted with routine nursing. Comparison was conducted on the effects of different programs on AMD patient nutrient intake, nutrition knowledge, vision-related quality of life, self-efficacy and best-corrected visual acuity (BCVA) at the beginning and at the end of the intervention (Clinical Trials.gov: ChiCTR2200063978).

RESULTS: The results indicated that the intake of energy, zinc, copper, calcium, vitamin C, vitamin E and lutein was significantly higher in the intervention group than in the control group (p < 0.001). The intake of protein was significantly higher in the intervention group than in the control group (p < 0.01), whereas the intake of fat was significantly lower in the intervention group (p < 0.001). However, there were no significant differences in the intakes of iron, vitamin A, vitamin D, or folic acid between the intervention and control group. Vision-related quality of life, nutritional knowledge and self-efficacy scores of intervention group were higher than that of control group (p < 0.001). The BCVA of the intervention group did not differ significantly from that of the control group (p > 0.05).

CONCLUSION: Our research demonstrates that the APP-based AIM-AMD nutrition management model offers patients comprehensive, accurate, and personalized guidance on dietary management.

The results of this study demonstrate that the AIM-AMD nutritional management model holds demonstrable clinical value in the nutritional management process of patients with AMD.

CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=175931, Identifier ChiCTR2200063978.},
}

Humans
*Macular Degeneration/diet therapy
Female
Male
Aged
*Mobile Applications
Quality of Life
Aged, 80 and over
Nutritional Status
Middle Aged
Visual Acuity
*Nutrition Therapy/methods

@article {pmid42756394,
year = {2026},
author = {Li, Z and Zhao, T and Ye, L and Li, R and Tian, H and Liao, R and Huang, L},
title = {Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate NaIO3-Induced Dry AMD by Delivering miR-486-3p to Inhibit Lipocalin-2-Mediated Ferroptosis.},
journal = {MedComm},
volume = {7},
number = {10},
pages = {e71000},
pmid = {42756394},
issn = {2688-2663},
abstract = {Dry age-related macular degeneration (AMD), affecting over 196 million people globally, represents the leading cause of irreversible blindness with limited disease-modifying therapies. The disease is characterized by progressive retinal pigment epithelium (RPE) degeneration driven by ferroptosis, an iron-dependent form of regulated cell death. While mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) show therapeutic promise, their mechanisms in counteracting RPE ferroptosis remain unexplored. Here, we prove that human umbilical cord MSC-derived EVs (hucMSC-EVs) significantly attenuate NaIO3-induced retinal degeneration, preserving retinal structure and improving visual function in mice. Transcriptomic profiling identified Lipocalin-2 (Lcn2) as a key ferroptosis-related target. MSC-EVs administration markedly downregulated Lcn2 and upregulated Gpx4 in NaIO3-induced models, demonstrating potent ferroptosis suppression. Furthermore, AAV-mediated Lcn2 overexpression induced AMD-like retinal pathology, which was effectively attenuated by subsequent MSC-EVs treatment. Small RNA sequencing reveals miR-486-3p as the key factor in the MSC-EVs, and dual-luciferase reporter assays confirm its direct binding to the Lcn2 3'UTR. Functional validation demonstrates that miR-486-3p agomir recapitulates the effects of MSC-EVs, including preservation of retinal structure and improvement of electrophysiological responses. Our findings establish a novel strategy where hucMSC-EVs deliver miR-486-3p to suppress Lcn2-mediated ferroptosis, offering a potential treatment for dry AMD.},
}

@article {pmid42754690,
year = {2026},
author = {Faes, L and Kubravi, S and Spooner, K and Thottarath, S and Sivaprasad, S and Fu, DJ and , },
title = {Macular neovascularisation subtype determines visual consequences of early fibro-atrophic remodelling in neovascular AMD: PRECISE study report 11.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42754690},
issn = {1476-5454},
abstract = {PURPOSE: To evaluate whether baseline well-delineated hyperreflective material (wdHRM) is associated with short-term visual outcome in treatment-naïve neovascular age-related macular degeneration (nAMD), whether this association differs by macular neovascularisation (MNV) subtype, and how wdHRM relates to atrophy-related OCT biomarkers.

METHODS: Multicentre observational analysis of 2036 treatment-naïve eyes (PRECISE cohort) completing three monthly aflibercept 2 mg injections. Best-corrected visual acuity (BCVA) at Visit 4 (V4) was modelled against baseline wdHRM using adjusted multivariable linear regression. Secondary analyses assessed subtype interaction and eye-level association with atrophy-related OCT biomarkers.

RESULTS: Mean BCVA improved from 58.0 to 62.6 letters by V4. Baseline wdHRM was present in 14.6% of eyes, and foveal-involving wdHRM independently predicted lower V4 BCVA (β =-6.60 letters, 95%confidence interval [CI]-8.18 to -5.02; p < 0.001). Foveal-involving baseline choroidal hypertransmission (HTM) showed a stronger adverse association (β =-8.98, 95%CI-10.97 to -6.98; p < 0.001). The wdHRM association differed by subtype (interaction p = 0.016), with adjusted BCVA reductions of -10.6 letters in Type 3 MNV, -4.8 in Type 2/mixed MNV, -4.1 in Type 1 MNV, and -1.0 in polypoidal choroidal vasculopathy. By V4, wdHRM increased to 21.0% and was associated with HTM and greater outer retinal disruption.

CONCLUSIONS: In treatment-naïve nAMD, baseline wdHRM is independently associated with poorer short-term visual outcome, particularly in Type 3 MNV. Short-term visual outcome should be interpreted in relation to both fibrosis-related and atrophy-related OCT biomarkers.},
}

@article {pmid42747171,
year = {2026},
author = {Bikbov, MM and Kazakbaeva, GM and Gilemzianova, LI and Panda-Jonas, S and Holz, FG and Jonas, JB},
title = {Safety of intravitreally applied epidermal growth factor receptor antibody panitumumab.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70235},
pmid = {42747171},
issn = {1755-3768},
abstract = {PURPOSE: To examine the safety of the epidermal growth factor (EGF) receptor antibody panitumumab intravitreally applied in patients with myopic macular degeneration (MMD) or neovascular age-related macular degeneration (AMD).

METHODS: Patients with MMD stage 4 underwent repeated intravitreal panitumumab injections in escalating doses, and patients with neovascular AMD received combined intravitreal ranibizumab/panitumumab injections, with single ranibizumab injections applied in between.

RESULTS: The study included 28 patients. In the first cohort, 11 highly myopic patients with MMD stage 4 (age: 66.8 ± 6.3 years) received intravitreal panitumumab injections in doses of 0.6 mg (4 eyes; 1 × 1 injection, 3 × 2 Injections), 1.2 mg (4 eyes; 1 × 1 injection; 2 × 2 injections; 1 × 3 injections) and 1.8 mg (3 eyes; 1 × 1 injection, 2 × 2 injections), respectively, in intervals of 3.6 ± 1.8 months (first to second injection), and 4.7 months (second to third injection). At 3.7 ± 0.4 years (median: 3.6 years; range: 3.5-4.7 years) after the first injection, ten patients were re-examined, with no change in axial length (30.6 ± 1.0 vs. 30.7 ± 1.3; p = 0.66). A second cohort included 17 eyes with neovascular AMD and receiving bimonthly combined panitumumab/ranibizumab (1.2 mg/0.5 mg) injections (mean: 2.4 ± 0.5 injections). The mean follow-up period was 11.0 ± 1.0 months (median: 11 months; range: 6-14 months). In none of the eyes of the first and second cohort, treatment-related systemic or intraocular adverse events were noted. Ocular side effects were hyposphagmata at the injection sites. Signs of intraocular inflammation were not detected in any eye. The morphology of the optic nerve head did not change significantly, nor did the IOP (14.5 ± 4.3 mmHg vs. 13.5 ± 1.5 mmHg; p = 0.30).

CONCLUSIONS: Repeated intravitreal panitumumab applications in various doses, single or combined with ranibizumab, were not associated with severe ocular or systemic side effects.},
}

@article {pmid42749023,
year = {2026},
author = {Sakai, D and Hirami, Y and Takagi, S and Yamamoto, M and Totani, K and Yamanari, M and Fujihara, M and Sugita, S and Maeda, T and Takahashi, M and Mandai, M and Kurimoto, Y},
title = {Ten-Year Survival of First-in-Human Autologous Induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Sheet Transplantation.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.09.005},
pmid = {42749023},
issn = {2468-6530},
abstract = {PURPOSE: This study aimed to report the 10-year follow-up results of the first-in-human study of induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) sheet transplantation, with a focus on long-term graft persistence assessed using multimodal imaging, including polarization-sensitive optical coherence tomography (PS-OCT)-based melanin evaluation.

DESIGN: Follow-up of a single patient PARTICIPANT: A patient with neovascular age-related macular degeneration METHODS: Autologous iPSC-derived RPE sheets were transplanted into the subretinal space in 2014.

MAIN OUTCOME MEASURES: Engraftment of the transplanted RPE sheet and preservation of the host retinal structure were evaluated using multimodal imaging, including color fundus photography, spectral-domain (SD)-OCT and PS-OCT, and near-infrared autofluorescence (NIRAF), throughout the post-transplantation period.

RESULTS: The patient was aged 88 years at the 10-year post-transplantation follow-up. There was stable anatomic appearance of the persistent subretinal pigmentation on color fundus photography. SD-OCT revealed the preservation of the outer nuclear layer over the graft. Choroidal thickness analysis indicated sustained structural preservation beneath the graft. PS-OCT demonstrated persistent depolarization signals of the RPE layer, which were separated from the overlying retina and corresponded to the pigmented area observed on color fundus photography. The combination of high polarimetric entropy on PS-OCT and low-to-iso-autofluorescence on NIRAF further delineated the grafted area, distinguishing it from healthy and atrophic regions.

CONCLUSIONS: Sustained preservation of the overlying neurosensory retina and underlying choroid, in conjunction with long-term pigment persistence, provides important evidence of the safety and structural stability of iPSC-based cell therapy. These findings support the potential of this approach for broader clinical application in regenerative medicine.},
}

@article {pmid42749828,
year = {2026},
author = {Lim, AY and Fox, S and Mahendra, S and Nugawela, M and Seeberan, R and Barnes, A and Amalfitano, F and Sivaprasad, S and Mahroo, OA},
title = {Visual impairment certifications in England over 16 years: annual numbers attributable to age-related macular degeneration, glaucoma, diabetes and hereditary eye disease.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42749828},
issn = {1476-5454},
}

@article {pmid42749868,
year = {2026},
author = {Cagini, C and Messina, M and Fiore, T and Chiruzzi, ML and Frenguelli, M and Crescenzi, L and Poddi, M},
title = {Short-term adjunctive use of a liposomal tear substitute after repeated intravitreal therapy: a randomized pilot study.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42749868},
issn = {1573-2630},
mesh = {Humans ; Pilot Projects ; Female ; Male ; Intravitreal Injections ; Liposomes ; Middle Aged ; *Dry Eye Syndromes/drug therapy/diagnosis/prevention & control/etiology ; Angiogenesis Inhibitors/administration & dosage ; Ophthalmic Solutions/administration & dosage ; Aged ; Follow-Up Studies ; *Lubricant Eye Drops/administration & dosage ; *Macular Degeneration/drug therapy ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Time Factors ; Aged, 80 and over ; Prospective Studies ; Tears ; },
abstract = {PURPOSE: This pilot study investigates the efficacy of a liposomal ophthalmic solution containing cross-linked hyaluronic acid, trehalose, and stearylamine in reducing the occurrence of dry eye-like signs and symptoms in patients undergoing repeated intravitreal treatment.

METHODS: Participants aged over 50 years old were randomly assigned to receive either standard therapy alone (Group 1) or standard therapy with additional eye drops (Group 2). Examinations included TBUT, Schirmer's test, fluorescein staining, the Ocular Surface Disease Index (OSDI), and the 5-item Dry Eye Questionnaire (DEQ-5) at baseline and day 15, with a 30-day telephone follow-up for OSDI reassessment.

RESULTS: Ninety patients with age-related macular degeneration or other retinal diseases requiring anti-VEGF (vascular endothelial growth factor) treatment were enrolled in the study. In Group 1, which comprised 20 males and 25 females, DEQ-5 scores did not exhibit any significant change between V0 and V1 (10.89 ± 2.71 to 10.57 ± 2.60, p = 0.173), while Group 2, composed of 18 males and 27 females, demonstrated a considerable reduction in DEQ-5 values (9.28 ± 3.24 to 8.00 ± 3.64, p < 0.0001). OSDI scores in Group 1 showed no relevant change between V0 and V1 (p = 0.497), whereas in Group 2 they improved significantly (p < 0.0001). Additionally, Group 2 had notable enhancements in TBUT and Schirmer tests (p < 0.0001), while Group 1 experienced a significant decrease in TBUT values alone (p = 0.026).

CONCLUSION: Chronic intravitreal therapy contributes to significant ocular surface impairment, which can be effectively mitigated by the administration of a tear substitute alongside the standard treatment.},
}

Humans
Pilot Projects
Female
Male
Intravitreal Injections
Liposomes
Middle Aged
*Dry Eye Syndromes/drug therapy/diagnosis/prevention & control/etiology
Angiogenesis Inhibitors/administration & dosage
Ophthalmic Solutions/administration & dosage
Aged
Follow-Up Studies
*Lubricant Eye Drops/administration & dosage
*Macular Degeneration/drug therapy
Treatment Outcome
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Time Factors
Aged, 80 and over
Prospective Studies
Tears

@article {pmid42751623,
year = {2026},
author = {Makhdoum, H and Alharbi, A and Alhazmi, S and Alrehaili, A and Afandi, R and Aljohani, G and Alharbi, K},
title = {Understanding anti-vascular endothelial growth factor medications: chemical properties, costs, and side effects.},
journal = {Journal of medicine and life},
volume = {19},
number = {7},
pages = {503-510},
pmid = {42751623},
issn = {1844-3117},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Angiogenesis Inhibitors/adverse effects/therapeutic use/economics/pharmacology ; Macular Degeneration/drug therapy ; Recombinant Fusion Proteins/therapeutic use/adverse effects ; Ranibizumab/therapeutic use ; Receptors, Vascular Endothelial Growth Factor ; },
abstract = {Vascular endothelial growth factor (VEGF) is an important driver of abnormal retinal neovascularization and increased vascular permeability. VEGF overexpression is associated with a number of retinal conditions, such as diabetic macular edema (DME), and neovascular age-related macular degeneration (nAMD). Anti-VEGF treatments have been the most common for these conditions and have improved vision by reducing abnormal blood vessel formation and leakage. This narrative review addressed the fact that the pharmacological properties, safety profiles, and cost-effectiveness of the currently marketed anti-VEGF intravitreal agents (i.e. bevacizumab, ranibizumab, aflibercept, brolucizumab, pegaptanib, and recently faricimab) differ and therefore, each of these agents, have their own unique molecular structure, target specificity, duration of action in the eye, and systemic circulation, each of which will affect the dosing intervals and treatment burden as well as the safety and adverse events associated with each drug. Aflibercept is a high-binding-affinity decoy receptor and is therefore distinct from faricimab, which is a dual-action (VEGF-A and angiopoietin-2) inhibitor. By contrast, ranibizumab, bevacizumab, brolucizumab, and pegaptanib are anti-angiogenic agents with different VEGF blockade profiles, which ultimately lead to distinct clinical outcomes and pharmacokinetic profiles. While anti-VEGF therapies are highly effective, the outcomes regarding safety, efficacy, and cost depend heavily on the study design and reflect the actual treatment paradigm and continuum of care within the healthcare system. The various attributes of agents should help personalize a patient's treatment approach while also addressing potential challenges related to the safety, efficacy, and longevity of treatment for retinal diseases.},
}

Humans
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Angiogenesis Inhibitors/adverse effects/therapeutic use/economics/pharmacology
Macular Degeneration/drug therapy
Recombinant Fusion Proteins/therapeutic use/adverse effects
Ranibizumab/therapeutic use
Receptors, Vascular Endothelial Growth Factor

@article {pmid42752553,
year = {2026},
author = {Osorio, DL and Kumar, A and Choi, A and Sodhi, I and Guo, C and Montaner, S},
title = {Angiopoietin-Like 4 Induces Upregulation of VEGF and sVCAM1 Through JNK/c-Jun and JAK2/STAT5 Signaling Pathways.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {11},
pages = {36},
doi = {10.1167/iovs.67.11.36},
pmid = {42752553},
issn = {1552-5783},
mesh = {Animals ; *Vascular Endothelial Growth Factor A/genetics/biosynthesis/metabolism ; *Angiopoietin-Like Protein 4 ; Mice ; Up-Regulation ; *Janus Kinase 2/metabolism ; Mice, Inbred C57BL ; Signal Transduction ; *Vascular Cell Adhesion Molecule-1/genetics/biosynthesis/metabolism ; *STAT5 Transcription Factor/metabolism ; Blotting, Western ; Cells, Cultured ; Disease Models, Animal ; *Angiopoietins/pharmacology ; },
abstract = {PURPOSE: Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine regulating angiogenesis, vascular permeability, and inflammation that is elevated, along with vascular endothelial growth factor (VEGF), in multiple ocular neovascular disorders, including ischemic retinopathies and neovascular age-related macular degeneration. However, the downstream signaling pathways that contribute to the effects of ANGPTL4 in ocular disease remain unclear.

METHODS: A phospho-kinase Proteome Profiler array was used to map pathways activated by recombinant ANGPTL4 in immortalized murine retinal endothelial cells (iRECs). Candidate signaling routes were assessed using pharmacologic inhibition and siRNA-mediated knockdown to define their roles in ANGPTL4-driven angiogenesis and effector upregulation. Findings were validated following intraocular ANGPTL4 delivery in C57BL/6J mice.

RESULTS: ANGPTL4 robustly activated the c-Jun N-terminal kinase (JNK)/c-Jun and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 5 (STAT5) axes in iRECs, a signature recapitulated in neurosensory retina in vivo. Inhibition of either pathway significantly reduced ANGPTL4-induced angiogenesis, identifying these pathways as critical effectors of ANGPTL4 signaling. ANGPTL4 induced secretion of VEGF, soluble vascular cell adhesion molecule 1 (sVCAM1), T-cell immunoglobulin and mucin domain 1 (TIM-1), and proliferin; however, only VEGF and sVCAM1 depended on JNK/c-Jun and JAK2/STAT5.

CONCLUSIONS: ANGPTL4 functions as a signaling hub that integrates different cues to activate JNK/c-Jun and JAK2/STAT5 and upregulate the expression of key pathogenic proteins including VEGF and sVCAM1. This work establishes these cascades as previously unrecognized effectors of ANGPTL4 signaling in the retina and brings important insight into the critical role that ANGPTL4 plays in neovascular retinal disease.},
}

Animals
*Vascular Endothelial Growth Factor A/genetics/biosynthesis/metabolism
*Angiopoietin-Like Protein 4
Mice
Up-Regulation
*Janus Kinase 2/metabolism
Mice, Inbred C57BL
Signal Transduction
*Vascular Cell Adhesion Molecule-1/genetics/biosynthesis/metabolism
*STAT5 Transcription Factor/metabolism
Blotting, Western
Cells, Cultured
Disease Models, Animal
*Angiopoietins/pharmacology

@article {pmid42753030,
year = {2026},
author = {Jang, B and Oh, R and Lee, TH and Yoon, CK and Choi, HJ and Choi, J and Kim, YG and Bae, K},
title = {Deep learning-derived retinal age gap and its associations with lifestyle, systemic, and ocular health in a health screening cohort.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42753030},
issn = {2509-2723},
abstract = {Individuals of the same chronological age differ in biological aging, and scalable, noninvasive markers are needed. The deep learning-derived retinal age gap (RAG) is a promising measure of retinal aging, but its associations with real-world health determinants remain unclear. We developed a multi-task model to predict retinal age using 29,530 fundus images from 7535 participants in a health screening cohort and evaluated RAG in cohort A for lifestyle, socioeconomic, and systemic factors (n = 5606) and cohort B for ocular diseases (n = 1810). The bias-corrected multi-task model trained on mixed data achieved the best performance, with a mean absolute error of 2.656 years and a Pearson correlation of 0.921 in cohort A and 2.529 years and 0.938 in cohort B. Higher RAG was significantly associated with smoking (ex-smokers, β = +0.46 years; current smokers, β = +0.50 years) and with clinical diabetes (+2.52 years); both survived false discovery rate (FDR) and Bonferroni correction, and the diabetes association persisted across all sequential covariate-adjustment sets. Married participants had lower RAG (β = -0.46 years), significant after FDR correction only. Hypertension and hyperlipidemia were not associated with RAG. In cohort B, RAG was significantly higher in eyes with age-related macular degeneration (β = +0.60 years) and cataract (β = +1.86 years) than in normal controls, both surviving corrections. RAG, an imaging-derived age-prediction residual, is therefore associated with lifestyle, systemic, and ocular health. Whether it reflects biological aging requires longitudinal validation against established aging biomarkers; at present, RAG suits population-level characterization better than individual-level risk stratification.},
}

@article {pmid42753946,
year = {2026},
author = {Ong, AY and Struvyen, RR and Merle, DA and Mendez, K and Ashourizadeh, H and Mukherjee, S and Lima-Cabrita, A and Chang, J and Wu, D and Pundlik, S and Vavvas, DG and Kim, IK and Miller, JW and Wu, Z and Keane, PA and Miller, JB and Husain, D and Lains, I},
title = {Association of reticular pseudodrusen burden and dark adaptation in non-advanced age-related macular degeneration: a cross-sectional and longitudinal study.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.09.003},
pmid = {42753946},
issn = {2468-6530},
abstract = {PURPOSE: Dark adaptation (DA) has emerged as a potential functional outcome for assessing age-related macular degeneration (AMD). While reticular pseudodrusen (RPD) have been linked to poorer DA, most studies to date have focused on qualitative RPD presence/absence or comprised small cross-sectional cohorts. This work aimed to assess how automated quantification of RPD area and volume relates to rod-mediated DA and its longitudinal decline in non-advanced AMD.

DESIGN: Prospective cross-sectional and longitudinal study.

PARTICIPANTS: Patients with non-advanced AMD and controls, all aged above 50, from the Massachusetts Eye and Ear AMD Biomarkers Study.

METHODS: All subjects underwent baseline multimodal retinal imaging and DA testing with a 20-minute extended protocol (AdaptDx, MacuLogix). Rod intercept time (RIT) and area under the dark adaptation curve (AUDAC) were calculated. A deep learning algorithm was employed to quantify RPD en face area (mm[2]) and volume (mm[3]), which were square- and cube-root transformed respectively for analysis. RPD extent within the DA testing locus was also measured. Linear mixed-effect models evaluated the relationship of RPD burden with DA metrics, accounting for age, sex, smoking, classic drusen volume and inter-eye correlation.

MAIN OUTCOME MEASURES: Association between RPD burden and dark adaptation (RIT and AUDAC) on a cross-sectional and longitudinal basis RESULTS: We included 545 eyes (52 early AMD, 285 intermediate AMD, 208 controls) from 310 patients (mean 69.6±7.4 years). 128 (23.5%) had RPD. Greater RPD en-face area and volume were associated with prolonged RIT (β 1.59, p=0.002 and β 9.29, p=9.78 x 10[-5] respectively) and higher AUDAC (β 0.032, p=2.15 x 10[-4] and β 0.166, p=5.88x10[-5] respectively). Overall macular RPD burden, rather than local density at the DA testing locus, was independently associated with worse AUDAC (β 0.005, p=0.001). In longitudinal analyses (n=204 eyes, mean 2.8±1.8 years), RPD presence (β 0.011, p=0.0067), en face area (β 0.012, p=4.48 x 10[-4]), and volume (β 0.054, p=2.11 x 10[-4]) were all significantly associated with a faster rate of AUDAC decline over time, and were predictive of AUDAC at any subsequent visit (β 0.048, p=6.72 x 10[-5] and β 0.198, p=2.02 x 10[-4]).

CONCLUSIONS: Quantitative RPD burden is independently associated with impaired rod-mediated DA and with subsequent functional decline, supporting its value as a prognostic structural biomarker for risk stratification and progression monitoring in non-advanced AMD.},
}