@article {pmid41535412,
year = {2026},
author = {García Cruz, MC and Flores Márquez, A and Morilla Ortega, A and Moreno Gutiérrez, JÁ and Barranco Rodríguez, M and Escarramán Reyes, J and García Casares, N and Chinchurreta Capote, A},
title = {Resilience and vision-related quality of life in advanced age-related macular degeneration: a brief clinical report.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41535412},
issn = {1476-5454},
}

@article {pmid41535097,
year = {2026},
author = {Carlà, MM and Crincoli, E and Catania, F and De Luca, L and Giannuzzi, F and Boselli, F and Gambini, G and Mateo, C and Rizzo, S},
title = {Advanced analysis of leading large language models for diagnostic accuracy in retinal imaging.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327634},
pmid = {41535097},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: To evaluate and compare the diagnostic capabilities of advanced large language models (LLMs) in interpreting ophthalmological fundus images across diverse pathologies.

METHODS: We evaluated eight leading multimodal LLMs (GPT-4.5, Claude 3.7 Sonnet, Grok-2, Deepseek Cognition V2, Qwen2 72B, Gemini 2.0 Pro, Llama 3 405B and Mixtral 8×22B) on their ability to interpret 100 fundus images representing various ophthalmological conditions. Performance was assessed using validated charts for diagnostic accuracy, specificity, sensitivity, consistency, relevance and explanation quality.

RESULTS: GPT-4.5 achieved the highest overall diagnostic accuracy (65.0%), followed by Gemini 2.0 Pro (63.0%). All models showed varied performance across pathology categories, with rhegmatogenous pathologies being most accurately identified (Gemini 2.0 Pro: 81.3%, GPT-4.5: 75.0%) and myopic maculopathy (mean accuracy 21.8%) being particularly challenging. The remaining models performed significantly worse: Deepseek Cognition V2 (52.0%), Claude 3.7 Sonnet (52.0%), Qwen2 72B (49.0%), Llama 3 405B (48.0%), Grok-2 (47.0%) and Mixtral 8×22B (46.0%). Lower-performing models frequently declined to provide diagnoses, with refusal rates from 8.0% (Claude 3.7 Sonnet) to 19.0% (Mixtral 8×22B).

CONCLUSION: Current LLMs show promising but limited capabilities in ophthalmological image interpretation. While performance on common conditions like retinal detachments and age-related macular degeneration is moderately good, significant challenges remain with rare conditions, myopic pathologies and complex vascular disorders. The competitive performance between GPT-4.5 and Gemini 2.0 Pro, with each excelling in different pathology categories, suggests that leveraging their complementary strengths might offer improved diagnostic support.},
}

@article {pmid41534822,
year = {2026},
author = {Zahran, L and Elnabawy, RH},
title = {Key optogenetic advances in retinal prostheses: A comparative narrative review.},
journal = {Brain research},
volume = {1874},
number = {},
pages = {150166},
doi = {10.1016/j.brainres.2026.150166},
pmid = {41534822},
issn = {1872-6240},
abstract = {This narrative review examines optogenetic strategies for retinal prostheses, which represent an advanced step in vision restoration, particularly for patients with retinitis pigmentosa and age-related macular degeneration. This review highlights the use of optogenetic stimulation to target high-density retinal ganglion cells (RGCs), focusing on developments like the FlexLED device. Opsins such as ChR2, ReaChR, and ChrimsonR, engineered for light sensitivity and faster responses, are critical for enhancing vision restoration. Combining optogenetic and electrical stimulation improves the reproducibility and specificity of RGC responses. Neuroimaging techniques like adaptive optics scanning laser ophthalmoscopy (AOSLO) help monitor cell activity, aiding in the development of visual repair methods. However, challenges remain in improving opsin sensitivity, gene delivery techniques, and ensuring long-term efficacy of retinal responses in patients. This review emphasizes the potential of optogenetic retinal prostheses to offer lasting, effective vision rehabilitation, significantly improving the quality of life for patients. This narrative review emphasizes that further research is needed to overcome current obstacles, such as improving opsin sensitivity and gene delivery techniques, to ensure long-term, effective vision restoration in patients.},
}

@article {pmid41533943,
year = {2025},
author = {Kramer, A and Rinsky, B and Elbaz-Hayoun, S and Khateb, S and Jaouni, T and Jaskoll, S and Tiosano, L and Durst, R and Chowers, I},
title = {Altered High-Density Lipoprotein Expression Pattern in the Aqueous Humor From Eyes With Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {73},
doi = {10.1167/iovs.66.15.73},
pmid = {41533943},
issn = {1552-5783},
mesh = {Humans ; *Aqueous Humor/metabolism ; Male ; Female ; Aged ; *Lipoproteins, HDL/metabolism ; Proteomics/methods ; Chromatography, Liquid ; Aged, 80 and over ; Tandem Mass Spectrometry ; *Wet Macular Degeneration/metabolism ; Middle Aged ; *Macular Degeneration/metabolism ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is associated with altered protein expression in the aqueous humor (AH). We aim to perform an unbiased proteomic analysis of the AH to identify proteomic signatures characterizing the disease's neovascular AMD (nAMD) and non-neovascular AMD (nnAMD) stages.

METHODS: AH samples were collected from eyes with nAMD (n = 39), nnAMD (n = 30), and healthy control eyes (n = 36). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze the AH proteome; differentially expressed proteins underwent functional analysis. Serum high-density lipoprotein cholesterol (HDL-C) levels were correlated with AH high-density lipoprotein (HDL) pathway proteins.

RESULTS: Seventeen proteins were upregulated and five were downregulated in nAMD eyes compared with healthy controls. Enriched pathways include the fibrinogen complex, the complement alternate, the spherical HDL particle, and the serine protease inhibitor. Forty-six proteins were upregulated in nAMD versus nnAMD, whereas nine were downregulated. Enriched pathways included the spherical HDL particle, peptidase S1A, membrane attack complex, Sushi domain, and complement alternate pathway. No differentially expressed proteins were found between nnAMD and control eyes. Upregulated proteins associated with the spherical HDL particle pathway in nAMD, including apolipoprotein A-I, apolipoprotein A-II, and paraoxonase 1, exhibited a negative correlation with serum HDL-C levels (r = -0.43, P = 0.012; r = -0.37, P = 0.031; and r = -0.52, P = 0.002, respectively).

CONCLUSIONS: HDL-associated proteins exhibit increased expression in AH of nAMD eyes, independent of serum HDL-C levels. These findings suggest that serum HDL-C may not accurately reflect ocular HDL particle levels, highlighting the role of retinal lipid dysregulation in nAMD.},
}

Humans
*Aqueous Humor/metabolism
Male
Female
Aged
*Lipoproteins, HDL/metabolism
Proteomics/methods
Chromatography, Liquid
Aged, 80 and over
Tandem Mass Spectrometry
*Wet Macular Degeneration/metabolism
Middle Aged
*Macular Degeneration/metabolism

@article {pmid41533930,
year = {2025},
author = {Kato, N and Haruta, M and Arai, R and Nagae, A and Sato, K and Furushima, K and Yoshida, S},
title = {Association of Molar Dose and Early Retinochoroidal Blood Flow Changes After Intravitreal Anti-Vascular Endothelial Growth Factor Therapy.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {56},
doi = {10.1167/iovs.66.15.56},
pmid = {41533930},
issn = {1552-5783},
mesh = {Humans ; Intravitreal Injections ; Retrospective Studies ; Recombinant Fusion Proteins/administration & dosage ; Receptors, Vascular Endothelial Growth Factor/administration & dosage ; Female ; Male ; *Choroid/blood supply ; *Angiogenesis Inhibitors/administration & dosage ; Aged ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Regional Blood Flow/physiology/drug effects ; Antibodies, Monoclonal, Humanized/administration & dosage ; Aged, 80 and over ; *Retinal Vessels/physiopathology/physiology ; Dose-Response Relationship, Drug ; Laser-Doppler Flowmetry ; *Wet Macular Degeneration/drug therapy/physiopathology ; Fluorescein Angiography ; Middle Aged ; Blood Flow Velocity ; Follow-Up Studies ; Visual Acuity ; Tomography, Optical Coherence ; },
abstract = {PURPOSE: The purpose of this study was to evaluate short-term intraocular blood flow changes post-intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection in patients with neovascular age-related macular degeneration (nAMD), compare reductions across 4 agents (brolucizumab, faricimab, aflibercept 2 mg, and aflibercept 8 mg), and examine correlations between each agent's molar dose and the magnitude of 30-minute blood flow change.

METHODS: This retrospective series included 61 eyes with nAMD (15 treated with brolucizumab, 15 with faricimab, 15 with aflibercept 2 mg, and 16 with aflibercept 8 mg). Laser speckle flowgraphy quantified mean blur rate (MBR) at the optic nerve head vessels (ONH MBR-vessel) and choroid (CHOR MBR) before and 30 minutes post-injection. Percent changes (%ONH MBR-vessel, %CHOR MBR) were compared among groups, and correlations with molar dose were assessed.

RESULTS: In the aflibercept 8 mg group, the mean percent changes were -11.2% ± 11.2% for ONH MBR-vessel (P = 0.001) and -13.7% ± 7.5% for CHOR MBR (P < 0.001). Pairwise comparisons showed no significant differences in %ONH MBR-vessel between aflibercept 8 mg and other agents. The reduction in %CHOR MBR was significantly greater with aflibercept 8 mg than with aflibercept 2 mg (P = 0.019). Molar dose was not significantly correlated with %ONH MBR-vessel, whereas %CHOR MBR showed a significant negative association with molar dose (Spearman ρ = -0.395, P = 0.002).

CONCLUSIONS: Aflibercept 8 mg produced a significant 30-minute reduction in ocular blood flow. Choroidal flow reduction was greater than with aflibercept 2 mg and negatively correlated with molar dose, suggesting a concentration-dependent hemodynamic effect.},
}

Humans
Intravitreal Injections
Retrospective Studies
Recombinant Fusion Proteins/administration & dosage
Receptors, Vascular Endothelial Growth Factor/administration & dosage
Female
Male
*Choroid/blood supply
*Angiogenesis Inhibitors/administration & dosage
Aged
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Regional Blood Flow/physiology/drug effects
Antibodies, Monoclonal, Humanized/administration & dosage
Aged, 80 and over
*Retinal Vessels/physiopathology/physiology
Dose-Response Relationship, Drug
Laser-Doppler Flowmetry
*Wet Macular Degeneration/drug therapy/physiopathology
Fluorescein Angiography
Middle Aged
Blood Flow Velocity
Follow-Up Studies
Visual Acuity
Tomography, Optical Coherence

@article {pmid41533927,
year = {2025},
author = {Li, Q and Liu, D and Zhang, M},
title = {Obstructive Sleep Apnea Accelerates Progression of Intermediate Age-Related Macular Degeneration: A Three-Year Prospective Cohort Study.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {59},
doi = {10.1167/iovs.66.15.59},
pmid = {41533927},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Disease Progression ; *Sleep Apnea, Obstructive/complications/physiopathology/diagnosis ; Prospective Studies ; Aged ; Middle Aged ; Visual Acuity/physiology ; Follow-Up Studies ; Polysomnography ; *Macular Degeneration/diagnosis/physiopathology ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/diagnosis/physiopathology ; Risk Factors ; Geographic Atrophy/diagnosis ; Fluorescein Angiography ; },
abstract = {PURPOSE: Obstructive sleep apnea (OSA) and age-related macular degeneration (AMD) share pathophysiological mechanisms involving oxidative stress and inflammation. We investigated whether OSA accelerates AMD progression in patients with intermediate AMD.

METHODS: This prospective cohort study enrolled 470 patients aged ≥50 years with intermediate AMD and age-matched healthy controls. After baseline polysomnography and multimodal retinal imaging, 470 participants were enrolled and stratified into AMD+OSA (n = 185), AMD-noOSA (n = 185), and healthy controls (n = 100). Of these, 391 completed the 36-month follow-up (AMD+OSA n = 153; AMD-noOSA n = 158; controls n = 80). The primary endpoint was composite AMD progression (central geographic atrophy, neovascular AMD, or ≥15-letter vision loss) over 36 months. Secondary endpoints included changes in visual acuity, drusen volume, and geographic atrophy area.

RESULTS: Of 391 participants completing follow-up (83.2% retention), the AMD+OSA group showed significantly higher progression rates. The primary endpoint occurred in 31.4% (48/153) of AMD+OSA versus 15.2% (24/158) of AMD-noOSA patients (P = 0.002). Visual acuity worsened by 0.15 versus 0.06 logarithm of the minimum angle of resolution (P < 0.001), and drusen volume increased by 0.05 versus 0.02 mm3 (P < 0.001), respectively. Cox regression revealed a dose-dependent relationship: mild OSA (hazard ratio [HR] = 1.45; 95% confidence interval [CI], 0.95-2.20; P = 0.08), moderate OSA (HR = 2.10; 95% CI, 1.35-3.28; P = 0.001), and severe OSA (HR = 2.80; 95% CI, 1.75-4.47; P < 0.001) versus no OSA.

CONCLUSIONS: OSA is an independent, dose-dependent risk factor for accelerated AMD progression. Screening and treating OSA in patients with intermediate AMD may represent a novel strategy to preserve vision.},
}

Humans
Female
Male
Disease Progression
*Sleep Apnea, Obstructive/complications/physiopathology/diagnosis
Prospective Studies
Aged
Middle Aged
Visual Acuity/physiology
Follow-Up Studies
Polysomnography
*Macular Degeneration/diagnosis/physiopathology
Tomography, Optical Coherence/methods
*Wet Macular Degeneration/diagnosis/physiopathology
Risk Factors
Geographic Atrophy/diagnosis
Fluorescein Angiography

@article {pmid41533916,
year = {2026},
author = {Lyu, A and Mungalsingh, MA and Silva, AE and Khan, S and Labreche, T and Leat, SJ and Woo, GC and Woo, S and Thompson, B and Cheong, AMY},
title = {Transcranial Direct Current Stimulation Does Not Enhance Perceptual Learning of Chinese Character Reading in Adults With Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {1},
pages = {16},
doi = {10.1167/iovs.67.1.16},
pmid = {41533916},
issn = {1552-5783},
mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Contrast Sensitivity/physiology ; *Learning/physiology ; *Macular Degeneration/physiopathology/therapy ; *Reading ; *Transcranial Direct Current Stimulation/methods ; Visual Acuity/physiology ; Visual Cortex/physiology ; *Visual Perception/physiology ; Language ; },
abstract = {PURPOSE: Macular degeneration impairs central vision, compelling patients to use their peripheral vision for reading, which is difficult due to reduced spatial resolution and crowding. Although perceptual learning improves reading, single-session anodal transcranial direct current stimulation (a-tDCS) over the visual cortex has shown inconsistent outcomes, with transient improvements observed in English reading but no benefit for Chinese reading in macular degeneration patients. This randomized controlled trial investigated whether combining multi-session a-tDCS with perceptual learning enhances Chinese reading performance in these patients compared to sham stimulation.

METHODS: Twenty Chinese-reading patients with macular degeneration (39-90 years old) were randomized to receive either active (n = 10) or sham (n = 10) a-tDCS during six sessions of rapid serial visual presentation (RSVP) reading training. Trained outcomes (RSVP reading) and untrained functions (sentence reading, crowding, contrast sensitivity, and visual acuity) were compared at baseline, 1 day, and 1 month post-training.

RESULTS: Perceptual learning significantly improved RSVP reading speed (P < 0.001) in both groups, with effects lasting at least a month. No additive effect of active versus sham a-tDCS was observed (group × time P = 0.99). Transfer effects to untrained functions were limited to visual acuity and critical print size for sentence reading.

CONCLUSIONS: Perceptual learning enhances Chinese reading performance in individuals with macular degeneration, but a-tDCS confers no additional benefit. This contrasts with previous results where non-invasive brain stimulation enhanced English reading in macular degeneration. The results emphasize the need for more refined neuromodulation strategies for improving logographic reading.},
}

Adult
Aged
Aged, 80 and over
Female
Humans
Male
Middle Aged
Contrast Sensitivity/physiology
*Learning/physiology
*Macular Degeneration/physiopathology/therapy
*Reading
*Transcranial Direct Current Stimulation/methods
Visual Acuity/physiology
Visual Cortex/physiology
*Visual Perception/physiology
Language

@article {pmid41533907,
year = {2026},
author = {Veernala, I and Cuamatzi-Castelan, AS and Rajesh, A and Gong, J and D'Souza, GJ and Lavine, JA},
title = {Levodopa Suppresses Choroidal Neovascularization Through a Tyrosinase-Dependent Dual Mechanism.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {1},
pages = {8},
doi = {10.1167/iovs.67.1.8},
pmid = {41533907},
issn = {1552-5783},
mesh = {Animals ; *Levodopa/pharmacology/therapeutic use ; *Choroidal Neovascularization/drug therapy/metabolism/prevention & control/pathology ; Mice ; *Monophenol Monooxygenase/metabolism ; Disease Models, Animal ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Dopamine D2/agonists/metabolism ; Choroid/drug effects ; Dopamine Agonists/pharmacology ; Signal Transduction ; },
abstract = {PURPOSE: Levodopa (L-DOPA), a precursor for melanin and dopamine, has been linked to reduced intravitreal injection burden and delayed onset of neovascular age-related macular degeneration (AMD). Further, L-DOPA and dopamine receptor D2 (DRD2) agonists inhibit laser-induced choroidal neovascularization (CNV). However, the contributions of endogenous versus exogenous L-DOPA signaling, their effects in alternative CNV models, and the contributions of DRD2 versus GPR143, the receptor for L-DOPA, signaling remain unresolved.

METHODS: Choroidal sprouting assays (CSA) were performed using wild-type (WT) and tyrosinase-mutant (Tyr-/-) mice with and without dopamine pathway agonists and antagonists. CNV number and area were measured in pigmented Vldlr-/- and albino Vldlr-/-Tyr-/- mice with and without L-DOPA or the DRD2 agonist quinpirole.

RESULTS: Endogenous L-DOPA deficiency (Tyr-/-) did not affect CSA sprouting or CNV in Vldlr-/- mice. Exogenous L-DOPA suppressed angiogenesis ex vivo in both WT and Tyr-/- choroidal explants in a dose-dependent manner. In vivo, L-DOPA reduced CNV lesion number, lesion area, and macrophage infiltration in albino but not pigmented Vldlr-/- mice. Dopamine and quinpirole produced modest anti-angiogenic effects, and eticlopride partially reversed L-DOPA inhibition in choroidal explants. Quinpirole suppressed CNV lesion number, lesion area, and macrophage infiltration in pigmented Vldlr-/- mice.

CONCLUSIONS: Our findings show that L-DOPA's anti-angiogenic effects are exogenous, more effective in tyrosinase-mutant mice, and mediated by both the DRD2 and non-DRD2 pathways, potentially GPR143. The saturation of GPR143 signaling in pigmented eyes provides a mechanistic basis for reduced responsiveness, highlighting the importance of pigmentation biology in the development of L-DOPA-based therapeutics.},
}

Animals
*Levodopa/pharmacology/therapeutic use
*Choroidal Neovascularization/drug therapy/metabolism/prevention & control/pathology
Mice
*Monophenol Monooxygenase/metabolism
Disease Models, Animal
Mice, Inbred C57BL
Mice, Knockout
Receptors, Dopamine D2/agonists/metabolism
Choroid/drug effects
Dopamine Agonists/pharmacology
Signal Transduction

@article {pmid41533899,
year = {2026},
author = {Yasuda, H and Nakamura, S and Shirakawa, A and Kuse, Y and Shimazawa, M},
title = {Inhibition of Pathological Mitochondrial Fission in Retinal Pigment Epithelium Mitigates Choroidal Neovascularization.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {1},
pages = {4},
doi = {10.1167/iovs.67.1.4},
pmid = {41533899},
issn = {1552-5783},
mesh = {Animals ; *Choroidal Neovascularization/metabolism/pathology/prevention & control/drug therapy ; *Mitochondrial Dynamics/drug effects/physiology ; Mice, Inbred C57BL ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Mice ; *Quinazolinones/pharmacology ; Disease Models, Animal ; Blotting, Western ; Fluorescein Angiography ; *Mitochondria/metabolism ; Cells, Cultured ; Dynamins/metabolism ; Male ; Vascular Endothelial Growth Factor A/metabolism ; },
abstract = {PURPOSE: Mitochondria are highly dynamic organelles that continuously undergo fission and fusion, and their dysfunction is associated with various age-related disorders. This study aimed to elucidate the role of mitochondrial fission in the development of choroidal neovascularization (CNV), a hallmark of neovascular age-related macular degeneration (AMD), and to evaluate the therapeutic potential of its pharmacological inhibition.

METHODS: The murine CNV model was created by laser photocoagulation using C57BL/6J mice. Expression changes of mitochondrial fission-related protein during CNV development were examined using western blotting and immunofluorescence. To assess the effectiveness of pharmacological inhibition of mitochondrial fission, the effects of mitochondrial division inhibitor-1 (Mdivi-1) and mitochondrial fusion promoter (M1) were evaluated by CNV area measurement, fluorescein angiography, and western blot analysis. The pro-angiogenic mechanisms associated with mitochondrial fission were further investigated in RPE cells cultured under hypoxic condition.

RESULTS: In a murine laser-induced CNV model, mitochondrial fission-related proteins increased in the retinal pigment epithelium (RPE)-choroid complex, and the high expression of phosphorylated dynamin-related protein 1 (DRP1) was observed in RPE cells surrounding the CNV lesion. Additionally, intravitreal injection of Mdivi-1 or M1 suppressed CNV formation, vascular leakage, and pro-angiogenic factor production. In RPE cells exposed to hypoxia, DRP1-mediated mitochondrial fission was rapidly activated, accompanied by increased mitochondrial reactive oxygen species production. Moreover, inhibition of mitochondrial fission suppressed mitochondrial bioenergetic dysfunction and the upregulation of vascular endothelial growth factor.

CONCLUSIONS: These findings support that pharmacological inhibition of activated mitochondrial fission could serve as a potential therapeutic approach for neovascular AMD.},
}

Animals
*Choroidal Neovascularization/metabolism/pathology/prevention & control/drug therapy
*Mitochondrial Dynamics/drug effects/physiology
Mice, Inbred C57BL
*Retinal Pigment Epithelium/metabolism/pathology/drug effects
Mice
*Quinazolinones/pharmacology
Disease Models, Animal
Blotting, Western
Fluorescein Angiography
*Mitochondria/metabolism
Cells, Cultured
Dynamins/metabolism
Male
Vascular Endothelial Growth Factor A/metabolism

@article {pmid41533868,
year = {2025},
author = {Guo, S and Gao, L and Cao, D and Huang, H and Ye, D and Lin, J and Meng, J and Xue, J and Li, Z and Li, J and Cheng, H},
title = {The Prevalence of Malnutrition and Early-Stage Age-Related Macular Degeneration: Using Three Nutritional Scoring Systems.},
journal = {Translational vision science & technology},
volume = {14},
number = {12},
pages = {25},
doi = {10.1167/tvst.14.12.25},
pmid = {41533868},
issn = {2164-2591},
mesh = {Humans ; *Macular Degeneration/epidemiology/diagnosis ; Female ; Male ; Aged ; *Malnutrition/epidemiology/diagnosis/complications ; Prevalence ; *Nutritional Status ; Middle Aged ; *Nutrition Assessment ; Aged, 80 and over ; Choroid/pathology/blood supply/diagnostic imaging ; },
abstract = {PURPOSE: To investigate the interrelationships among malnutrition, choroidal parameters, and early-stage age-related macular degeneration (AMD), particularly the reticular pseudodrusen (RPD) phenotype, and to assess the predictive value of three nutritional scores.

METHODS: A total of 177 eyes were included in the study, categorized into control (n = 54), AMD (n = 55), and AMD-RPD (n = 68) groups based on fundus features. Nutritional status was assessed using the Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI). Choroidal vascular index (CVI) and choroidal thickness (ChT) were measured.

RESULTS: Nutritional scores indicated a progressive decline in nutritional status from control to AMD to AMD-RPD. Compared with the control group, both AMD and AMD-RPD individuals had significantly worse CONUT, GNRI, and PNI scores (all P ≤ 0.01). Compared with the AMD group, AMD-RPD had significantly lower GNRI and PNI scores (both P < 0.001). CVI was positively correlated with GNRI (r = 0.308, P < 0.001) and PNI (r = 0.284, P < 0.001). The predictive value of all three nutritional scores for both AMD and AMD-RPD was demonstrated, with GNRI and PNI showing utility in differentiating RPD from AMD.

CONCLUSIONS: Malnutrition is associated with early-stage AMD phenotypes and choroidal vascular abnormalities may underlie this link. GNRI and PNI may help identify high-risk RPD individuals and support early nutritional assessment and intervention.

TRANSLATIONAL RELEVANCE: Integrating these nutritional scores may enhance collaboration between ophthalmologists and dietitians, enabling better detection and management of AMD and RPD in clinical practice.},
}

Humans
*Macular Degeneration/epidemiology/diagnosis
Female
Male
Aged
*Malnutrition/epidemiology/diagnosis/complications
Prevalence
*Nutritional Status
Middle Aged
*Nutrition Assessment
Aged, 80 and over
Choroid/pathology/blood supply/diagnostic imaging

@article {pmid41533856,
year = {2026},
author = {Owsley, C and McGwin, G and Gao, L and Clark, ME and Gooden, L and Thomas, TN and Goerdt, L and Curcio, CA},
title = {Natural History of Visual Function Changes Over Three Years in Normal Aging and in Early and Intermediate Age-Related Macular Degeneration: ALSTAR2.},
journal = {Translational vision science & technology},
volume = {15},
number = {1},
pages = {16},
doi = {10.1167/tvst.15.1.16},
pmid = {41533856},
issn = {2164-2591},
mesh = {Humans ; *Macular Degeneration/physiopathology ; Aged ; *Visual Acuity/physiology ; Female ; Male ; Contrast Sensitivity/physiology ; *Aging/physiology ; Middle Aged ; Dark Adaptation/physiology ; Aged, 80 and over ; },
abstract = {PURPOSE: The purpose of this study was to evaluate change in visual functions over 3 years in normal macular health, and early and intermediate age-related macular degeneration (AMD) including tests of rod-, cone-, and mixed rod-cone-mediated visions; and to evaluate whether visual function change over 3 years meets the minimal clinically important difference (MCID), defined as meaningful to patients in everyday life.

METHODS: Eight visual functions were evaluated at baseline and 3-year follow-up (acuity, low luminance acuity, photopic and mesopic contrast sensitivity, mesopic and scotopic light sensitivity, and rod-mediated dark adaptation [RMDA] at 5 degrees and 12 degrees). The Age-Related Eye Disease Study (AREDS) 9-step classification system defined AMD severity.

RESULTS: In normal aging and intermediate AMD, 6 of 8 visual functions had statistically significant worsening over 3 years; mesopic contrast sensitivity and mesopic light sensitivity, respectively, showed no change. In early AMD, five of eight visual functions showed worsening over time, with photopic and mesopic contrast sensitivity and scotopic sensitivity unchanged. The largest percentage of eyes in each group meeting MCID was RMDA at 5 degrees or 12 degrees (38%-55%). The lowest percentage of eyes meeting MCID was visual acuity and photopic contrast sensitivity (0%-10%).

CONCLUSIONS: Whereas most visual functions evaluated have statistically significant worsening over 3 years in normal aging to intermediate eyes, the percentage of eyes reaching MCID was low for most visual functions except RMDA, which met MCID for almost half the eyes.

TRANSLATIONAL RELEVANCE: The natural history of change in visual function over time in normal aging to intermediate AMD should be characterized in terms of MCID, not only statistical significance.},
}

Humans
*Macular Degeneration/physiopathology
Aged
*Visual Acuity/physiology
Female
Male
Contrast Sensitivity/physiology
*Aging/physiology
Middle Aged
Dark Adaptation/physiology
Aged, 80 and over

@article {pmid41533847,
year = {2026},
author = {Miladinovic, A and Biscontin, A and Ajcevic, M and Kresevic, S and Accardo, A and Tognetto, D and Inferrera, L},
title = {Neurosymbolic AI Framework for Explainable Retinal Disease Classification From OCT Images.},
journal = {Translational vision science & technology},
volume = {15},
number = {1},
pages = {6},
doi = {10.1167/tvst.15.1.6},
pmid = {41533847},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/classification/diagnostic imaging/diagnosis ; *Neural Networks, Computer ; Retrospective Studies ; Deep Learning ; },
abstract = {PURPOSE: Accurate classification of retinal diseases such as dry age-related macular degeneration, wet AMD, epiretinal membrane, full-thickness macular hole (MH), lamellar MH, and central serous chorioretinopathy (CSC) is essential for effective treatment and clinical decision-making. Traditional deep learning models, however, often struggle with imbalanced datasets and lack interpretability, limiting their translational applicability in ophthalmology.

METHODS: We propose a neurosymbolic framework that integrates a convolutional neural network (CNN) with a symbolic reasoning layer based on expert-defined clinical rules. A total of 10,846 optical coherence tomography images were retrospectively collected and categorized into seven diagnostic classes: dry AMD, wet AMD, epiretinal membrane, full-thickness MH, lamellar MH, central serous chorioretinopathy, and healthy retinas.

RESULTS: Our neurosymbolic model achieved macro-precision 0.83, recall 0.82, and F1 0.81, on internal dataset, having slightly better performance than the CNN (0.64/0.83/0.68). On the external dataset, it retained superior performance, macro-precision 0.85, recall 0.79, F1 0.78, versus the CNN (0.73/0.64/0.59).

CONCLUSIONS: Our hybrid neurosymbolic framework introduces a unified paradigm that couples symbolic reasoning with a conventional CNN, improving diagnostic performance while delivering transparent, clinically interpretable decisions. It is particularly effective for rare and complex conditions that often challenge end-to-end deep learning models.

TRANSLATIONAL RELEVANCE: By integrating symbolic clinical logic with visual pattern recognition, the neurosymbolic model fosters trust in artificial intelligence-assisted diagnostics and supports precise, explainable decision-making in retinal care.},
}

Humans
*Tomography, Optical Coherence/methods
*Retinal Diseases/classification/diagnostic imaging/diagnosis
*Neural Networks, Computer
Retrospective Studies
Deep Learning

@article {pmid41533007,
year = {2026},
author = {Li, J and Wang, T and Lu, W and Jishkariani, D and Tsourkas, A and Kaja, S and Vining, KH and Thussananutiyakul, J and Spence, A and Nair, RM and Dunaief, JL and Mitchell, CH},
title = {PLGA Nanoparticles Restore Acidic pH and Degradative Function to Compromised Lysosomes with Cy3-Labeling Providing Enhanced Tracking to Lysosomes.},
journal = {American journal of physiology. Cell physiology},
volume = {},
number = {},
pages = {},
doi = {10.1152/ajpcell.00494.2025},
pmid = {41533007},
issn = {1522-1563},
support = {EY013434//HHS | NIH | National Eye Institute (NEI)/ ; EY015537//HHS | NIH | National Eye Institute (NEI)/ ; EY001538//HHS | NIH | National Eye Institute (NEI)/ ; //Illinois Society for the Prevention of Blindness (ISPB)/ ; //Research to Protect Blindness/ ; //Penn Undergraduate Research Mentoring Program (PURM)/ ; //Eversight/ ; //Richard A Perritt MD Charitable Foundation/ ; //Dr. John P. and Therese E. Mulcahy Endowed Professorship in Ophthalmology/ ; //This work was partially supported by the Collaborative Research Grant (KV) from the Institute of Regenerative Medicine at the University of Pennsylvania& and the REgeneration and ReSToration of Function/ ; },
abstract = {Lysosomal dysfunction and elevated lysosomal pH are hallmark features of age-related neurodegenerative diseases including Age-related Macular Degeneration (AMD), Alzheimer's Disease (AD), and Parkinson's Disease (PD). Restoring lysosomal acidity is important for maintaining enzymatic degradation, preventing protein aggregation, and reducing cellular waste accumulation in degenerating tissues. Acidic nanoparticles represent a promising therapeutic strategy to normalize lysosomal pH; however, accurate monitoring of their delivery, retention, and dosage is critical for rigorous evaluation. To address this, we developed fluorescently labeled poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles conjugated with Cyanine3 amine (Cy3). Nanoparticle uptake was systematically optimized, achieving over 90% delivery to lysosomes of induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells. Uptake rates varied among adjacent cells. Once internalized, nanoparticles demonstrated remarkable stability, with no detectable change in concentration, distribution, or size for at least 28 days. iPS-RPE cells exhibited higher nanoparticle internalization compared to the ARPE-19 cell line and optic nerve head astrocytes. The capacity of the nanoparticles to restore function to stressed lysosomes was confirmed by their ability to reacidify lysosomes, restore cathepsin B activity and increase levels of active cathepsin D. The nanoparticles also reduced levels of LC3II in astrocytes treated with chloroquine, indicating they can also restore autophagy rates. In summary, this study demonstrates the value of Cy3 labeling for enhanced nanoparticle tracking to lysosomes. The findings also identify PLGA nanoparticles as powerful tools for restoring degradative lysosomal function and autophagy in cells undergoing lysosomal stress.},
}

@article {pmid41532690,
year = {2026},
author = {Wagner, M and Leutloff, CJ and Rauscher, FG},
title = {A Simulation Procedure for Stereological Correction of Early AMD Lesion Sizes Observed in Single OCT-B-Scans.},
journal = {Translational vision science & technology},
volume = {15},
number = {1},
pages = {21},
doi = {10.1167/tvst.15.1.21},
pmid = {41532690},
issn = {2164-2591},
mesh = {*Tomography, Optical Coherence/methods ; Humans ; *Macular Degeneration/diagnostic imaging/pathology ; Aged ; Female ; Male ; Computer Simulation ; Aged, 80 and over ; Middle Aged ; },
abstract = {PURPOSE: Early lesions caused by age-related macular degeneration (AMD) are imaged by optical coherence tomography (OCT) in unprecedented detail. Most probably, however, the sampling plane of an OCT scan meets a given lesion noncentrally, and the observed sizes of its diameter, cross-sectional area, and volume must be stereologically corrected.

METHODS: Stereological corrections are obtained by a simulation procedure, which is applied to the leading scans in a consecutive sample of 100 early AMD participants.

RESULTS: Mean corrections for lesion diameter, cross-sectional area and volume amount to +9.1%, +32.0%, and +46.6%, respectively. After correction, AMD stage classifications with respect to the 125-µm diameter cutpoint had to be changed for seven participants.

CONCLUSIONS: Simulation results confirm that for lesions pictured and measured in OCT scans - regardless of the accuracy of OCT imaging - stereological correction of observed sizes is compelling and unavoidable.

TRANSLATIONAL RELEVANCE: Categorial AMD classifications based on observed OCT data must be reexaminated after stereological correction.},
}

*Tomography, Optical Coherence/methods
Humans
*Macular Degeneration/diagnostic imaging/pathology
Aged
Female
Male
Computer Simulation
Aged, 80 and over
Middle Aged

@article {pmid41531643,
year = {2025},
author = {Das, D and Chawla, B and Lomi, N and Grover, S and Narayan, A},
title = {AI in the Shadows: Unveiling the Strengths and Blind Spots of Medios AI Retinal Screening in Cancer Care.},
journal = {Cureus},
volume = {17},
number = {12},
pages = {e99002},
doi = {10.7759/cureus.99002},
pmid = {41531643},
issn = {2168-8184},
abstract = {Introduction Artificial intelligence (AI) is increasingly being integrated into ophthalmic diagnostics, offering potential for efficient screening of common retinal diseases. The Medios AI system by Remidio (Singapore, Singapore), designed for use with a smartphone-based fundus camera, claims to detect diabetic retinopathy (DR), age-related macular degeneration (ARMD), and glaucoma. However, its performance in complex clinical settings such as ocular oncology remains underexplored. This study aims to evaluate both the diagnostic capabilities and limitations of the Medios AI system when applied to a diverse cohort of oncology patients. Materials and methods An observational study was conducted over three months in an ocular oncology clinic. Ninety-eight cancer patients (196 eyes) underwent fundus photography using the Remidio smartphone-based fundus imaging system. The images were analyzed using the Medios AI algorithm. AI-generated findings were compared with clinical evaluations by an experienced ophthalmologist to identify diagnostic concordance and discrepancies. Additional attention was paid to the system's imaging capabilities, including its ability to capture wide-field or montage images. Result The AI system accurately identified glaucomatous cupping in three patients, flagged two cases of DR, and detected signs of ARMD in two patients-all consistent with clinical examination. However, eight patients with leukemic retinopathy were incorrectly flagged as having DR, revealing a lack of specificity in distinguishing vascular retinal pathologies. The system also failed to detect optic atrophy, a critical neuro-ophthalmic finding in oncology patients. A technical limitation was also noted: the inability of the Remidio system to generate montage or wide-field images, restricting visualization of the peripheral retina. Conclusion While the Medios AI system demonstrates promise in identifying common retinal pathologies such as DR, ARMD, and glaucoma, its limitations are significant in the oncology context. The inability to distinguish similar hemorrhagic retinopathies, failure to detect optic nerve atrophy, and lack of wide-field imaging capabilities underscore the need for cautious implementation. Integration of AI tools must be accompanied by expert clinical oversight, especially in specialized settings where retinal presentations are complex and atypical.},
}

@article {pmid41529750,
year = {2026},
author = {Arokia Vijaya Anand, M and Yang, CJ and Wang, WL and Yao, CH and Lai, JY},
title = {Marine-derived polysaccharides enhance the drug delivery mechanism in the management of ocular diseases: A review.},
journal = {International journal of biological macromolecules},
volume = {340},
number = {Pt 2},
pages = {150199},
doi = {10.1016/j.ijbiomac.2026.150199},
pmid = {41529750},
issn = {1879-0003},
abstract = {Ocular drug delivery remains significantly challenging due to complex anatomical and physiological barriers, poor bioavailability, and inefficient drug absorption. These limitations highlight the requirement for advanced delivery systems to overcome the ocular barrier and enable efficacious therapeutic outcomes. This review explores the potential of marine-derived polysaccharides as innovative carriers for ocular applications, emphasizing their potential as drug-delivery mechanisms to enhance drug retention, permeation, and bioavailability through advanced nanoplatforms. Polysaccharides such as κ-carrageenan, agarose, alginate, chitosan, hyaluronic acid, heparan sulfate, and chondroitin sulfate possess physicochemical, biocompatible, biodegradable, and mucoadhesive properties, making them ideal materials for ocular drug delivery. Notably, marine-derived polysaccharides have been reported to significantly improve ocular delivery performance, achieving up to a 3-fold increase in corneal permeability, higher drug accumulation in the aqueous humor (>47% vs. ∼20%), and approximately 3.6-3.8-fold enhancement in precorneal retention, while also enabling intelligent systems such as pH- and light-responsive drug release. These polymers have been engineered into various delivery platforms, including nanoparticles, micelles, dendrimers, nanosuspensions, hydrogels, and implants. Such systems promote sustained (long-acting), targeted (site-specific), and intelligent (stimuli-responsive) drug release, thereby significantly enhancing precorneal retention and therapeutic efficacy. These approaches are particularly relevant for treating various corneal diseases, including glaucoma, diabetic retinopathy, ocular inflammation, and age-related macular degeneration. The article also emphasizes the potential of emerging strategies to transform ocular drug delivery by offering customizable, stimuli-responsive, and patient-friendly therapeutic options. However, further in-depth research is crucial to optimize formulations, evaluate long-term safety, and address regulatory challenges for successful clinical translation.},
}

@article {pmid41529093,
year = {2026},
author = {Maatouk, CM and Hyman, MJ and Shah, A and Smith, SR and Yehia, M and Moir, J and Gonnah, R and Flores, A and Hariprasad, S and Skondra, D},
title = {Association Between Metformin and Other Diabetic Medications and Five-year Onset of New Neovascular Age-related Macular Degeneration Diagnosis.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-10},
doi = {10.3928/23258160-20251110-01},
pmid = {41529093},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: Neovascular age-related macular degeneration (nAMD) is a sight-threatening condition with growing prevalence, but few therapies exist to prevent its development. This study investigates whether metformin reduces the odds of new nAMD diagnosis.

PATIENTS AND METHODS: This was a case-control study using a nationwide insurance claims database of patients ages 55 and older with newly diagnosed nAMD from January 2008 to December 2019. Multivariable conditional logistic regression was utilized to determine how various exposures impacted the odds of new nAMD diagnosis.

RESULTS: Among 55,080 cases with new nAMD diagnosis and 55,066 matched controls, any metformin exposure reduced 5-year odds of new nAMD diagnosis compared to individuals not on metformin (odds ratio [OR]: 0.94; 95% CI: 0.90 to 0.99). Insulin and sulfonylurea exposures were also protective. These findings were consistent in subgroup analyses of patients with diabetes without diabetic retinopathy.

CONCLUSION: Metformin may reduce the 5-year odds of developing nAMD, particularly in diabetic patients without diabetic retinopathy.},
}

@article {pmid41529041,
year = {2026},
author = {Helmy, YA and Rahman, NK and Rahman, KT and Groppe, M and Bindra, MS and Latasiewicz, M},
title = {Comparison of intravitreal and subretinal tPA for acute submacular haemorrhage: A retrospective study.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251413662},
doi = {10.1177/11206721251413662},
pmid = {41529041},
issn = {1724-6016},
abstract = {PurposeThis study compares the anatomical and functional outcomes of two treatments for acute submacular haemorrhage (SMH): pars plana vitrectomy with subretinal recombinant tissue plasminogen activator (tPA) and gas tamponade versus intravitreal tPA and gas injection.MethodsA retrospective single-centre study was conducted of patients treated for acute SMH at Buckinghamshire Healthcare NHS Trust between January 2016 and December 2022. Patients received either intravitreal tPA and gas ± anti-VEGF (Group A) or pars plana vitrectomy with subretinal tPA and gas tamponade ± anti-VEGF (Group B). The primary outcome was anatomical success, defined as displacement of haemorrhage from the fovea. Secondary outcomes were visual acuity (VA) improvement, central foveal thickness (CFT) reduction, and complication rates.ResultsEighty eyes from 73 patients (mean age: 79.8 ± 11.5 years; 57.5% female) were analysed, with 53 eyes in Group A and 27 in Group B. Anatomical success was achieved in 71.6% of Group A and 77.8% of Group B. VA improved in 66% of Group A and 63% of Group B. CFT decreased by over 50% in both groups. No statistically significant differences were found between the two treatment groups and in anatomical or functional improvement.ConclusionIn this real-world study, both approaches effectively displaced SMH and improved vision with comparable outcomes, suggesting that treatment selection may be best determined by patient-specific and logistical factors.},
}

@article {pmid41528844,
year = {2026},
author = {Wang, SK and Li, J and Nair, S and Kosaraju, R and Chen, Y and Zhang, Y and Kundaje, A and Liu, Y and Wang, N and Chang, HY},
title = {Single-cell multiome and enhancer connectome of human retinal pigment epithelium and choroid nominate causal variants in macular degeneration.},
journal = {Cell reports},
volume = {45},
number = {1},
pages = {116814},
doi = {10.1016/j.celrep.2025.116814},
pmid = {41528844},
issn = {2211-1247},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide. Genome-wide association studies (GWASs) of AMD have identified dozens of risk loci that may house disease targets. However, variants at these loci are largely noncoding, making it difficult to assess their function and whether they are causal. Here, we present a single-cell gene expression and chromatin accessibility atlas of human retinal pigment epithelium (RPE) and choroid to systematically analyze both coding and noncoding variants implicated in AMD. We employ HiChIP and activity-by-contact modeling to map enhancers in these tissues and predict cell and gene targets of risk variants. We further perform allele-specific self-transcribing active regulatory region sequencing (STARR-seq) to functionally test variant activity in RPE cells, including in the context of complement activation. Our work nominates pathogenic variants and mechanisms in AMD and offers a rich and accessible resource for studying diseases of the RPE and choroid.},
}

@article {pmid41475683,
year = {2025},
author = {Bianchi, MJ and Sunness, JS and Applegate, CA},
title = {Reading Speed Patterns in Eyes with Geographic Atrophy and Good Visual Acuity.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.12.020},
pmid = {41475683},
issn = {2468-6530},
}

@article {pmid41527550,
year = {2026},
author = {Wu, P and Lin, M and Chen, Q and Chew, EY and Lu, Z and Peng, Y and Dong, H},
title = {AMD-Mamba: A Phenotype-Aware Multi-modal Framework for Robust AMD Prognosis.},
journal = {Machine learning in medical imaging. MLMI (Workshop)},
volume = {16241},
number = {},
pages = {150-160},
pmid = {41527550},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, making effective prognosis crucial for timely intervention. In this work, we propose AMD-Mamba, a novel multi-modal framework for AMD prognosis, and further develop a new AMD biomarker. This framework integrates color fundus images with genetic variants and socio-demographic variables. At its core, AMD-Mamba introduces an innovative metric learning strategy that leverages AMD severity scale score as prior knowledge. This strategy allows the model to learn richer feature representations by aligning learned features with clinical phenotypes, thereby improving the capability of conventional prognosis methods in capturing disease progression patterns. In addition, unlike existing models that use traditional CNN backbones and focus primarily on local information, such as the presence of drusen, AMD-Mamba applies Vision Mamba and simultaneously fuses local and long-range global information, such as vascular changes. Furthermore, we enhance prediction performance through multi-scale fusion, combining image information with clinical variables at different resolutions. We evaluate AMD-Mamba on the AREDS dataset, which includes 45,818 color fundus photographs, 52 genetic variants, and 3 socio-demographic variables from 2,741 subjects. Our experimental results demonstrate that our proposed biomarker is one of the most significant biomarkers for the progression of AMD. Notably, combining this biomarker with other existing variables yields promising improvements in detecting high-risk AMD patients at early stages. These findings highlight the potential of our multi-modal framework to facilitate more precise and proactive management of AMD.},
}

@article {pmid41526441,
year = {2026},
author = {Agarwal, D and Bhargava, A and Alsharif, MH and Saeed, S and Alsharif, NHM},
title = {Automatic diagnosis of age-related macular degeneration using machine learning and image processing techniques.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-35428-2},
pmid = {41526441},
issn = {2045-2322},
}

@article {pmid41525679,
year = {2026},
author = {Bindi, J and Choi, R},
title = {Novel Surgical Approach to Submacular Hemorrhage in the Setting of Extensive Pan-retinal Photocoagulation.},
journal = {Retinal cases & brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001865},
pmid = {41525679},
issn = {1937-1578},
abstract = {PURPOSE: To describe a novel surgical approach for managing submacular hemorrhage (SMH) in the setting of extensive panretinal photocoagulation (PRP) where conventional displacement techniques are limited by chorioretinal adhesions.

METHODS: We report the case of a 73-year-old monocular woman with neovascular age-related macular degeneration (AMD) and dense PRP scars who presented with an acute, fovea-involving SMH. A modified pars plana vitrectomy (PPV) was performed using submacular tissue plasminogen activator (tPA), perfluorocarbon liquid (PFCL) tamponade to direct blood toward three small retinotomies, active aspiration, and silicone oil placement.

RESULTS: This strategy achieved substantial clot evacuation and anatomic resolution. The patient's final visual acuity improved to 20/200.

CONCLUSION: Multiple small retinotomies with PFCL-assisted drainage may serve as a viable alternative surgical technique for SMH in eyes with extensive PRP scarring, where retinal adhesions preclude conventional displacement methods.},
}

@article {pmid41524889,
year = {2026},
author = {Chen, S and Wang, G and Guan, X and Wang, C and Xiao, Y and Li, X and Hong, S and Zhou, Y and You, Y and Fu, Y and Wang, Y and Zhang, Y and Zhao, H and Zhang, Y and Cheng, Y and Guo, H and Xie, H},
title = {Air pollutants, genetic susceptibility, and the risk of age-related macular degeneration: a large prospective cohort study.},
journal = {European journal of epidemiology},
volume = {},
number = {},
pages = {},
pmid = {41524889},
issn = {1573-7284},
support = {82373667//National Natural Science Foundation of China/ ; 82171025//National Natural Science Foundation of China/ ; 2018YFC2000203//National Key Research and Development Program of China/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide. However, evidence regarding the relationship between air pollution and AMD is limited, and the modifying effect of genetic susceptibility on this association remains unknown. A total of 445,237 participants without AMD at baseline were included from the UK Biobank. The concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), particulate matter (PM2.5, PM10, PM2.5-10) were collected by using land-use regression models. Air pollution score (APS) was constructed through summing each pollutant weighted by the regression coefficients with AMD from single-pollutant model. Cox proportional hazard models were used to evaluate hazard rations (HRs) and 95% confidence intervals (95%CIs) of associations between air pollutants and polygenic risk score (PRS) with incident AMD. During a median follow-up of 13.83 years, we observed 9,635 incident AMD events. The HR (95%CI) of incident AMD for each standard deviation increase in NO2, NOx, PM2.5, PM10, and APS were 1.04(1.02, 1.06), 1.03(1.01, 1.05). 1.04(1.02, 1.07), 1.02(1.00, 1.04), and 1.04(1.02, 1.06), respectively. Significant additive interaction effects of NO2, NOx, PM2.5-10, APS and PRS with incident risk of AMD were observed, with the relative excess risk due to the interaction (RERI), attributable proportion (AP), and their 95% CIs of 0.10(0.01, 0.18) and 0.05(0.01, 0.11) for NO2, 0.11(0.01, 0.19) and 0.05(0.02, 0.10) for NOx, 0.15(0.06, 0.23) and 0.08(0.03, 0.13) for PM2.5-10, and 0.12(0.03, 0.20) and 0.06(0.01, 0.11) for APS, respectively. Compared with participants exposed to low level of above air pollutants and low PRS, those exposed to high air pollution and high PRS had almost double incident risk of AMD [HR(95%CI) ranged from 1.83(1.68, 1.99) to 2.03(1.86, 2.21)]. Long-term exposure to air pollutants NO2, NOx, PM2.5, and PM10 showed positive associations with increased risk of AMD, which could be further enhanced by genetic susceptibility.},
}

@article {pmid41524752,
year = {2026},
author = {Kilani, A and Vogt, D and Moysidi, V and Assaf, A and Wolf, A and Vounotrypidis, E},
title = {VEGF-inhibitor switch trial in poor-responsive neovascular age-related macular degeneration: assessing brolucizumab vs. faricimab: VISTA study.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41524752},
issn = {1435-702X},
abstract = {PURPOSE: To compare short-term (12 weeks) and long-term (48 weeks) anatomical and functional outcomes after switching to brolucizumab (BRZ) or faricimab (FAR) under a treat-and-extend (TAE) regimen without an initial loading phase in eyes with poor-responsive neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective, single-center study included eyes with poor-responsive nAMD previously treated with anti-VEGF agents that were switched to BRZ or FAR between 2022 and 2025. Functional outcomes (best-corrected visual acuity [BCVA]) and anatomical parameters (central subfield thickness [CST], fibrovascular pigment epithelial detachment [fvPED] height, intraretinal/subretinal fluid [IRF/SRF], subretinal hyperreflective material [SHRM]) were assessed at baseline, week 12, and week 48. Injection frequency, interval extension, and safety were recorded.

RESULTS: Sixty-six eyes (41 BRZ, 25 FAR) were included. At 12 weeks, BCVA remained stable (BRZ 0.49 logMAR, FAR 0.40; p = 0.10). CST decreased significantly in both groups, greater with BRZ (243 μm vs. 280 μm; p = 0.04). Mean injections (2.95 vs. 3.2; p = 0.12) and intervals (5.9 vs. 5.6 weeks; p = 0.90) were comparable; no intraocular inflammation (IOI) occurred. At 48 weeks, BCVA was numerically better with FAR (0.20 vs. 0.49 logMAR; p = 0.08). CST reduction was sustained andcomparable (259 µm vs. 260 µm; p = 0.50). FAR achieved greater fvPED reduction (110 µm vs. 160 µm; p = 0.022). BRZ required fewer injections (6.3 vs. 7.2; p = 0.009) with similar intervals (9.4 vs. 9.9 weeks; p = 0.80). Mild IOI occurred in two BRZ eyes (4.9%) and none with FAR.

CONCLUSIONS: In poor-responsive nAMD, switching to BRZ or FAR under a TAE regimen without upload achieved stable vision, sustained CST reduction, and comparable treatment burden over one year. FAR showed greater fvPED regression and a slight functional trend, while BRZ achieved faster fluid resolution with fewer injections.},
}

@article {pmid41524233,
year = {2026},
author = {Li, Y and Zhang, Y and Wong, G and Kam, KW and Ho, M and Au, S and Zhang, XJ and Ng, MP and Ip, P and Young, AL and Pang, CP and Tham, CC and Chen, LJ and Yam, JC},
title = {Associations between the Mediterranean lifestyle and incident age-related eye diseases: a longitudinal analysis from the UK Biobank.},
journal = {Journal of global health},
volume = {16},
number = {},
pages = {04015},
doi = {10.7189/jogh.16.04015},
pmid = {41524233},
issn = {2047-2986},
mesh = {Humans ; Female ; Male ; Aged ; United Kingdom/epidemiology ; Middle Aged ; Longitudinal Studies ; *Macular Degeneration/epidemiology ; *Glaucoma/epidemiology ; *Cataract/epidemiology ; Incidence ; *Diet, Mediterranean/statistics & numerical data ; Prospective Studies ; Biological Specimen Banks ; Risk Factors ; Life Style ; UK Biobank ; },
abstract = {BACKGROUND: The Mediterranean lifestyle (MEDLIFE) is generally considered to have a positive effect on several health outcomes. However, little is known about its impact on age-related eye diseases. We aimed to assess the effect of MEDLIFE on the risk of three such diseases: cataract, glaucoma, and age-related macular degeneration (AMD).

METHODS: We included 113 829 participants from the UK Biobank who were free of age-related eye diseases at baseline and followed them up prospectively for disease occurrence. Adherence to MEDLIFE was assessed using 25 items, categorised under three blocks: 'Mediterranean food consumption' (block 1), 'Mediterranean dietary habits' (block 2), and 'physical activity, rest, social habits' (block 3). We used a Cox proportional hazard model to examine the associations of the MEDLIFE index and each of its blocks with incident age-related eye diseases.

RESULTS: During a median follow-up of 10.5 years, 9954 cases of cataract, 1956 cases of glaucoma, and 1736 cases of AMD were identified. We noted an inverse association between the MEDLIFE index and new-onset cataract (P-value for trend = 0.005). A one-point increment in the MEDLIFE score was associated with a 1.5% (95% confidence interval (CI) = 0.7-2.3) reduction in the risk of cataract, and with a 2.4% (95% CI = 0.5-4.3) reduction in AMD incidence. Analysis of MEDLIFE blocks indicated that block 2 (hazard ratio (HR) = 0.97; 95% CI = 0.95-0.99) and block 3 (HR = 0.97; 95% CI = 0.95-0.99) were associated with lower risk of cataract. Block 2 was further related to reduced risk of AMD (HR = 0.95; 95% CI = 0.91-0.99). Although we found no association between the MEDLIFE index and incident glaucoma, block 3 was associated with lower glaucoma risk (HR = 0.94; 95% CI = 0.90-0.98).

CONCLUSIONS: Higher adherence to MEDLIFE was associated with decreased incidence of cataract and AMD, while the 'physical activity, rest, and social interactions' block was related to a lower risk of glaucoma. Our findings suggest that MEDLIFE may serve as a potential behavioural intervention for preventing age-related eye diseases.},
}

Humans
Female
Male
Aged
United Kingdom/epidemiology
Middle Aged
Longitudinal Studies
*Macular Degeneration/epidemiology
*Glaucoma/epidemiology
*Cataract/epidemiology
Incidence
*Diet, Mediterranean/statistics & numerical data
Prospective Studies
Biological Specimen Banks
Risk Factors
Life Style
UK Biobank

@article {pmid41524223,
year = {2026},
author = {Kong, L and Han, X and Qi, S and Li, D and Zhang, J and Zhang, L and Zhang, S and Jiang, Q and Yan, B and Zhao, C},
title = {MSC-Derived Exosomal lnc-AGT-3: A Novel Anti-Angiogenic Target in Age-Related Macular Degeneration Through p53 Signaling Pathway.},
journal = {Aging cell},
volume = {25},
number = {2},
pages = {e70377},
doi = {10.1111/acel.70377},
pmid = {41524223},
issn = {1474-9726},
support = {82530031//National Natural Science Foundation of China/ ; 82020108006//National Natural Science Foundation of China/ ; 82501299//National Natural Science Foundation of China/ ; //Open Research Funds of the State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University./ ; },
mesh = {Humans ; *Exosomes/metabolism ; *RNA, Long Noncoding/metabolism/genetics ; *Tumor Suppressor Protein p53/metabolism ; *Mesenchymal Stem Cells/metabolism ; Signal Transduction ; *Macular Degeneration/genetics/metabolism/pathology ; Animals ; Mice ; *Angiogenesis Inhibitors/pharmacology ; Choroidal Neovascularization/genetics/pathology ; Male ; Female ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a major cause of irreversible vision impairment in elderly populations, characterized by pathological angiogenesis beneath the macula. Although anti-VEGF therapies have demonstrated clinical effectiveness, significant challenges including drug resistance and the need for frequent intravitreal injections persist. As natural nanovesicles, exosomes derived from mesenchymal stem cell (MSC) can mediate intercellular communication, making them an attractive alternative for modulating cellular processes. This study explored the anti-angiogenic effects of MSC-derived exosomes in nAMD, with particular emphasis on the role of a specific exosomal lncRNA lnc-AGT-3. Our results showed that lnc-AGT-3 expression was reduced in both nAMD patients and choroidal neovascularization (CNV) models, and its overexpression effectively inhibited pathological angiogenesis in vitro and in vivo. Mechanistically, lnc-AGT-3 enhanced the p53 signaling pathway by blocking the ubiquitination and degradation of p53 and ultimately inhibited neovascularization, a process potentially linked to its direct interaction with heterogeneous nuclear ribonucleoprotein K (hnRNP K). Our findings position MSC-derived exosomes enriched with lnc-AGT-3 as an innovative therapeutic paradigm for nAMD, acting through p53 pathway modulation to potentially overcome current treatment limitations.},
}

Humans
*Exosomes/metabolism
*RNA, Long Noncoding/metabolism/genetics
*Tumor Suppressor Protein p53/metabolism
*Mesenchymal Stem Cells/metabolism
Signal Transduction
*Macular Degeneration/genetics/metabolism/pathology
Animals
Mice
*Angiogenesis Inhibitors/pharmacology
Choroidal Neovascularization/genetics/pathology
Male
Female

@article {pmid41524032,
year = {2026},
author = {Chu, J and Haddadin, RI and Gill, M},
title = {Successful Cataract Surgery in a Patient with a Port Delivery System Implant for Diabetic Macular Edema.},
journal = {Case reports in ophthalmology},
volume = {17},
number = {1},
pages = {26-31},
pmid = {41524032},
issn = {1663-2699},
abstract = {INTRODUCTION: The Port Delivery Platform (PDS) with ranibizumab is a novel, surgically implanted device designed for continuous intraocular anti-VEGF delivery, approved for neovascular age-related macular degeneration and other retinal vascular diseases, including diabetic macular edema (DME) and diabetic retinopathy. While it can reduce treatment burden, the PDS implant introduces unique surgical considerations, particularly during subsequent ocular procedures.

CASE PRESENTATION: We report a case of successful cataract extraction and intraocular lens implantation in a 72-year-old female with a PDS implant for DME, enrolled in the Pagoda trial. Cataract surgery was performed via clear corneal incisions while carefully avoiding manipulation of the conjunctiva or implant. The procedure was uneventful, and the implant remained stable intraoperatively and postoperatively. The patient experienced improved visual acuity and underwent an uncomplicated implant refill after 15 days with confirmation of adequate implant coverage at the 6-month follow-up.

CONCLUSION: This case highlights key surgical considerations to preserve implant integrity and conjunctival health during cataract surgery in eyes with PDS implants. To our knowledge, this is the first report of cataract surgery in a PDS-implanted eye outside a clinical trial, emphasizing that standard phacoemulsification techniques can be safely adapted with proper precautions in this context.},
}

@article {pmid41524001,
year = {2026},
author = {Lischke, R and Krause, SM and Rauchegger, T and Haas, G and Koubek, M and Nowosielski, Y and Rehak, M},
title = {Intraocular inflammation after intravitreal injection of faricimab-a case series including one case of bilateral choroidal involvement.},
journal = {International journal of ophthalmology},
volume = {19},
number = {1},
pages = {185-192},
pmid = {41524001},
issn = {2222-3959},
abstract = {AIM: To report and analyze cases of sterile intraocular inflammation (IOI) following intravitreal faricimab injections in patients treated for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

METHODS: This double-center case series included nine eyes of six patients who developed uveitis after faricimab therapy. Comprehensive clinical evaluation was performed, including slit-lamp examination, intraocular pressure (IOP) measurement, fluorescein and indocyanine green angiography (ICGA), and laboratory tests. Inflammatory responses were treated with topical or systemic corticosteroids, and patients were monitored for visual acuity and inflammatory activity.

RESULTS: The incidence of IOI was 0.8% per patient (Innsbruck) and 0.23% (Czechia), with inflammation typically occurring between the third and sixth injection (mean interval: 10d post-injection). Inflammatory presentations ranged from anterior uveitis to posterior segment involvement. One notable case demonstrated novel choroidal hypofluorescent lesions on angiography, suggesting deeper ocular involvement. The mean patient age was 76y; five of six affected patients were female. All cases responded to local and systemic corticosteroids, with full recovery of initial visual acuity.

CONCLUSION: Sterile IOI after faricimab appears to be a rare but relevant adverse event. Although the incidence falls within expected ranges for anti-vascular endothelial growth factor (anti-VEGF) agents, the observed choroidal involvement represents a potentially new safety signal. Prompt diagnosis and corticosteroid therapy are effective in all cases. Our findings support the need for vigilant post-marketing surveillance and further studies to better understand the underlying mechanisms and risk factors of faricimab-associated inflammation.},
}

@article {pmid41520727,
year = {2026},
author = {Zhu, S and Zhang, J and Jiang, X and Peng, C and Liu, H and Qian, F},
title = {Biologics-device combinations: Enabling prolonged therapies in the posterior segment ocular disease.},
journal = {Advanced drug delivery reviews},
volume = {},
number = {},
pages = {115773},
doi = {10.1016/j.addr.2026.115773},
pmid = {41520727},
issn = {1872-8294},
abstract = {Posterior segment ocular diseases (e.g., age-related macular degeneration and diabetic retinopathy, etc.) often necessitate frequent intravitreal (IVT) injections of biologics, due to the rapid drug clearance and formidable ocular barriers. While molecular engineering strategies and high-concentration protein formulations could extend the administration intervals to a certain extent, they are confronted with critical challenges, protein aggregation, high viscosity, and limited duration. This has spurred the development of innovative biologics-device combination products, which represent a paradigm shift towards prolonged therapy. This comprehensive review examines the latest advancements of these combination platforms, including refillable implants (e.g., SUSVIMO®), encapsulated cell technology (e.g., ENCELTO™), and recombinant adeno-associated virus (rAAV) vectors (e.g., LUXTURNA®). The progress in biologics - device combination technologies has significantly reduced the frequency of ocular injections. However, substantial hurdles, such as instability caused by material-biologics interactions, potential risks during the sterilization and manufacturing processes, safety risks, and the evolving regulatory landscape, still need to be addressed. Achieving a balance between the stability of biologics and advanced device design, enhancing long-term safety, and developing responsive smart systems with real-time monitoring and feedback capabilities remain crucial for the advancement of next-generation ophthalmic therapies.},
}

@article {pmid41520064,
year = {2026},
author = {Hanson, RLW and Airody, A and Sivaprasad, S and McKibbin, M and Morland, AB and Peto, T and Chakravarthy, U and Gale, RP and , },
title = {Early detection of neovascular age-related macular degeneration in the second eye reduces intravitreal treatment burden: FASBAT report 2.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41520064},
issn = {1476-5454},
support = {OAP030A2401T//Novartis | Novartis Pharmaceuticals UK Limited (Novartis UK)/ ; },
abstract = {BACKGROUND/OBJECTIVES: To investigate if early detection of neovascular age-related macular degeneration (nAMD) in the second eye is associated with a reduced number of intravitreal treatments compared with the first eye using data from the EDNA/FASBAT trial.

SUBJECTS/METHODS: Post-hoc analysis of 117 participants receiving standard clinical care during the FASBAT study. Assessments were at enrolment and at an average of 18.9 (SD = 10.2) and 30.5 (SD = 9.7) months in the first eye. Assessment of the second eye was made at the onset of nAMD (as participants were monitored for conversion) and at 12- and 24-months. The annualised injection rate for first eyes and the actual rate for second eyes are reported alongside visual acuity (VA) and optical coherence tomography (OCT) characteristics.

RESULTS: In second eyes the annualised number of treatments was lower both in year 1 (second eyes mean = 6.4, SD = 3.4 vs mean = 7.2, SD = 1.9 in first eyes) and in year 2 (second eyes mean = 5.8, SD = 2.9; versus mean = 6.2, SD = 2.7 in first eyes). Second eyes had better VA at the point of conversion to nAMD (mean = 74.1, SD = 9.9) compared with the first eyes at baseline (mean = 55.6, SD = 15.3) which was maintained until 24 months (second eye: mean = 73.6, SD = 9.9; first eye: mean = 53.2, SD = 19.3). Highly reflective material was detected less frequently in second eyes compared to first eyes at clinical visits.

CONCLUSIONS: Compared to first eyes, early detection of nAMD in the second eye is beneficial in terms of better maintenance of visual acuity, reduced intravitreal treatment burden, and improved anatomical findings after 2 years of treatment.},
}

@article {pmid41519739,
year = {2026},
author = {Thomsen, AK and Steffensen, MA and Gotfredsen, K and Vorum, H and Honoré, B and Nissen, MH and Sørensen, TL},
title = {CD8+ T cell aging is associated with macular neovascularization area change in neovascular age-related macular degeneration: a prospective cohort study.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-025-04570-2},
pmid = {41519739},
issn = {1471-2415},
}

@article {pmid41519611,
year = {2026},
author = {Cornejo-Uixeda, S and Borrás-Blasco, J and Valcuende-Rosique, A and Gil, LP and Monteagudo-Martinez, N and Merino, V},
title = {Dosing interval optimization and persistence with faricimab in age-related macular degeneration: An observational study in real-world clinical practice.},
journal = {Farmacia hospitalaria : organo oficial de expresion cientifica de la Sociedad Espanola de Farmacia Hospitalaria},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.farma.2025.12.002},
pmid = {41519611},
issn = {2171-8695},
abstract = {OBJECTIVE: To evaluate treatment persistence and dosing interval extension with faricimab in neovascular age-related macular degeneration (nAMD) in real-world practice.

METHODS: Retrospective observational study conducted in a tertiary hospital (March 2024-March 2025). Patients receiving faricimab (treatment-naïve or pre-treated with anti-VEGF therapy), with ≥1 post-loading dose, were included. Dosing intervals were analyzed at baseline, 6 and 12 months, Adherence was assessed with the medication possession ratio (MPR), with >80% considered adherent. Persistence was defined as the time from treatment initiation to discontinuation or end of follow-up. Persistence was estimated using Kaplan-Meier survival analysis.

RESULTS: We included 129 patients (148 eyes), mean age 74.5 ± 8.85 years; 55% were female. A total of 39 patients (30.2%) were treatment-naïve and 90 (69.8%) were pretreated. At 12 months, 48.8% of naïve and 55.5% of pretreated patients achieved 8-12 weeks intervals. Mean persistence was 12.2 months (SD 0.2; 95% CI: 11.8-12.6). The median was not reached by the end of the study. Persistence rate was 93% at 6 and 12 months. Only one patient discontinued due to inefficacy. No serious adverse events or endophthalmitis occurred.

CONCLUSIONS: Faricimab showed excellent persistence and extended dosing intervals in real-world practice. This is the first study specifically evaluating faricimab real-world persistence in nAMD.},
}

@article {pmid41519383,
year = {2026},
author = {Chang, A and Sun, X and Iida, T and Lai, TYY and Wong, TY and Cheung, CMG and Lee, WK and Zhang, X and Schulze, A and Schmidt-Ott, UM and Zhao, M and Hasanbasic, Z and Leal, S and Chen, SJ and , },
title = {Intravitreal aflibercept 8 mg versus 2 mg in Asian patients with neovascular age-related macular degeneration: 48-week analysis of the Phase 3 PULSAR trial.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100278},
doi = {10.1016/j.apjo.2026.100278},
pmid = {41519383},
issn = {2162-0989},
abstract = {PURPOSE: To evaluate 1-year efficacy and safety of aflibercept 8mg in Asian patients with neovascular age-related macular degeneration (nAMD) in the PULSAR (NCT04423718) trial.

DESIGN: Subgroup analysis of the Phase 3 PULSAR trial.

METHODS: Patients aged ≥50 years with nAMD were randomized to receive intravitreal aflibercept 8 mg every 12 (8q12) or 16 (8q16) weeks, or aflibercept 2 mg every 8 weeks (2q8), following 3 initial monthly injections. Outcomes included change from baseline in best-corrected visual acuity (BCVA) and central subfield retinal thickness (CRT), durability, and safety at week (W) 48.

FINDINGS: Overall, 234 Asian patients participated and received study treatment (8q12 [n = 74], 8q16 [n = 77], and 2q8 [n = 83]). At W48, the least squares (LS) mean (95% CI) BCVA change from baseline was +9.9 (6.9, 12.9), +9.2 (7.1, 11.2), and +7.6 (4.7, 10.5) letters in the 8q12, 8q16, and 2q8 groups, respectively. The LS mean (95% CI) change in CRT from baseline to W48 for the 8q12, 8q16, and 2q8 groups was -141 (-152, -129), -156 (-167, -146), and -142 (-155, -129) µm, respectively. Most patients receiving 8q12 (85%) or 8q16 (87%), maintained their randomized dosing interval, through W48. The safety profile of aflibercept 8mg was comparable to aflibercept 2mg.

CONCLUSIONS: Aflibercept 8mg was effective and well tolerated in Asian patients with nAMD, with demonstrated improvements in functional and anatomic outcomes comparable to aflibercept 2mg at W48. Aflibercept 8mg outcomes were achieved with fewer injections than with aflibercept 2mg, consistent with overall PULSAR results.},
}

@article {pmid41519378,
year = {2026},
author = {Jeong, H and Eppel, PS and Kaelber, DC and Singh, RP and Talcott, KE},
title = {Malabsorption Syndromes and Risk of Age-Related Macular Degeneration: Evidence from Real-World Data.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.01.002},
pmid = {41519378},
issn = {2468-6530},
abstract = {PURPOSE: Despite mechanistic links connecting malnutrition and gut microbiome with retinal health, clinical research exploring the relationship between malabsorption syndromes and age-related macular degeneration (AMD) remains limited. This study compared the risks of AMD diagnosis in patients with and without various malabsorption syndrome diagnoses.

DESIGN: Retrospective cohort study of aggregated, de-identified patient data from multiple healthcare organizations across the United States using the TriNetX U.S. Collaborative Research Network in 11/2025.

PARTICIPANTS: Adults with a cataract-related International Classification of Diseases (ICD) encounter diagnosis codes and no baseline AMD ICD encounter diagnosis codes were divided into groups based on the presence of ICD encounter diagnosis codes for celiac disease (CeD), ulcerative colitis (UC), Crohn's disease (CrD), chronic pancreatitis (CP), and short bowel syndrome (SBS). Within the CP cohort, patients with pancreatic enzyme replacement therapy (PERT) prescription orders were subanalysis. For each cohort, a corresponding control cohort of patients without the respective ICD encounter diagnosis codes was created.

METHODS: The study and control cohorts were propensity-matched 1:1 on demographic factors, comorbidities, and disease-related conditions and prescription orders. The matched cohorts were compared on the risk of having AMD ICD encounter diagnoses.

MAIN OUTCOME MEASURE: Risk ratios (RR) and 95% confidence intervals (CI) of having an AMD ICD encounter diagnosis code with an accompanying retinal optical coherence tomography Common Procedural Terminology code. Significance was defined as CI ≤0.9 or ≥1.1.

RESULTS: Compared to controls without IBD, the CrD cohort (n=9,537, RR=1.42, CI=1.16-1.74), but not the UC cohort (n=15,039, RR=1.28, CI=1.09-1.51), had a higher risk of having early/intermediate AMD. CP was associated with an increased risk of AMD (n=12,856, RR=1.82, CI=1.53-2.16), even in the PERT subset (n=3,812, RR=1.83, CI=1.35-2.48). SBS (n=3,747) was associated with an increased risk of advanced/exudative AMD (RR=1.98, CI=1.31-2.98), but not early/intermediate AMD (RR=1.28, CI=0.96-1.71). CeD was not associated with increased AMD risk (n=9,315, RR=1.09, CI=0.88-1.35).

CONCLUSIONS: Chronic non-infectious causes of malabsorption syndromes-CrD, CP, and SBS-may represent underrecognized risk factors of AMD. This explorative study adds clinical evidence for a potential role of the gut-retina axis in the pathogenesis of AMD.},
}

@article {pmid41519100,
year = {2026},
author = {Naux, G and Bellot, L and Le Pabic, E and Mouriaux, F and Maucourant, Y},
title = {[Efficacy and safety of switching from Eylea® and Lucentis® to Ranivisio® in exudative age-related macular degeneration and its impact on treatment costs].},
journal = {Journal francais d'ophtalmologie},
volume = {49},
number = {2},
pages = {104757},
doi = {10.1016/j.jfo.2025.104757},
pmid = {41519100},
issn = {1773-0597},
abstract = {INTRODUCTION: The goal of this study was to investigate the efficacy and safety of therapeutic switch of intravitreal injections (IVT) from ranibizumab 10mg/mL (Lucentis®) and aflibercept 40mg/mL (Eylea®) to FYB201 (Ranivisio®) in exudative age-related macular degeneration (AMD). This study includes an analysis of the direct medical cost of managing exudative AMD. The data studied included the mean injection interval in the year preceding the switch and the 9 months following, the longest dry interval over this period, the change in central retinal thickness, tolerance data, the sum of visit costs, treatment costs and an estimate of transportation costs.

MATERIALS AND METHODS: Fifty-nine eyes of 46 patients treated for exudative AMD were included. Twenty-one eyes were treated with Lucentis® and 38 eyes with Eylea® before being switched to Ranivisio® between February 2023 and May 2024. The primary endpoint was the change in mean inter-injection interval in the pre-switch year versus the mean inter-injection interval in the 3 to 9 months post-switch.

RESULTS: Patients received a mean of 7.5 IVT of anti-VEGF per eye in the pre-switch year, with a mean inter-injection interval of 6.2 weeks in Treat-and-Extend (TaE) schedule. The switch resulted in an extension of the mean inter-injection interval to 7.1 weeks (P=0.0004) and an extension of the longest dry interval (7.5 versus 6.39, P=0.0057) in the following 3 to 9 months. A reduction in central retinal thickness was observed at 3 months (247μm versus 261μm, P=0.0067), and no adverse effects were noted. In the year prior to switch, total medical costs per patient amounted to €9,397, with €6,542.00 (70%) in medication costs, €2,035.50 (21%) in ophthalmologic follow-up costs and €819.60 (9%) in transportation costs. After the switch, with a mean Ranivisio® inter-injection interval of 7.1 weeks, the annual treatment cost per eye was estimated at €2,388.00 for 7.33 annual IVTs.

DISCUSSION: This study is consistent with data in the literature demonstrating the benefits of therapeutic switches in extending inter-injection intervals and improving retinal dryness, probably due to this method being a work-around for tachyphylaxis.

CONCLUSION: Switching from Eylea® and Lucentis® to Ranivisio® is effective in exudative AMD, with a good safety profile, and could help to reduce treatment costs.},
}

@article {pmid41518383,
year = {2026},
author = {Tanaka, F and Mino, T and Moriguchi, Y and Nagahama, H and Sakai, H and Tamura, M and Akiba, M and Enaida, H},
title = {Exploratory investigation of OCTA-VISTA for longitudinal monitoring of neovascular age-related macular degeneration treatment.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41518383},
issn = {1435-702X},
support = {22K09792//KAKENHI/ ; },
}

@article {pmid41518379,
year = {2026},
author = {Mhmud, H and Vermeulen, JP and Adanc, B and Klevering, JBJ and Groenink-Lindenhovius, C and Tigchelaar, OAM and Ponsioen, TL and Klaver, CCW and Witmer, AN},
title = {Real-world treatment outcomes of aflibercept versus bevacizumab for neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41518379},
issn = {1435-702X},
}

@article {pmid41517415,
year = {2025},
author = {Rodriguez-Vidal, C and Galletero Pandelo, L and Martínez-Alday, N and Bande, M and Blanco Teijeiro, MJ},
title = {Ultrasound-Enhanced Assessment of Vitreous Status in Exudative AMD: Associations with Neovascular Phenotypes, Treatment Burden, and Functional Outcomes.},
journal = {Journal of clinical medicine},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/jcm15010167},
pmid = {41517415},
issn = {2077-0383},
abstract = {Background/Objectives: The influence of the vitreoretinal interface on neovascular age-related macular degeneration (nAMD) remains poorly characterized. Most previous studies relied solely on macular optical coherence tomography (OCT), which provides limited information about global posterior vitreous detachment (PVD). This study evaluated (1) whether ultrasonography-defined PVD status differs between nAMD eyes and healthy controls, and (2) whether baseline PVD influences macular neovascularization (MNV) phenotype and functional outcomes following anti-vascular endothelial growth factor (anti-VEGF) therapy. Methods: In this prospective longitudinal study, treatment-naïve nAMD eyes and population-based healthy controls underwent dynamic B-scan ultrasonography and spectral-domain OCT. PVD was categorized as absent, partial, or complete. nAMD eyes received intravitreal aflibercept according to a treat-and-extend protocol and were followed for 12 months. Structural parameters-including subretinal fluid (SRF), intraretinal fluid (IRF), and central foveal thickness-along with best-corrected visual acuity (BCVA) were recorded. A multivariable linear regression model was performed to assess whether PVD independently predicted BCVA gain after adjusting for age, baseline BCVA, MNV subtype, SRF, atrophy, and number of injections. Results: Absence of PVD was significantly more frequent in nAMD eyes than in controls (p < 0.001), whereas complete PVD prevalence was comparable. In nAMD, absence of PVD was associated with a higher prevalence of MNV type 2 (p = 0.032), while partial/complete PVD correlated with type 1 lesions. After 12 months, eyes without PVD achieved the greatest visual improvement (mean BCVA gain +0.34 ± 0.26), outperforming eyes with complete PVD (p = 0.026). A multivariable model confirmed that absence of PVD was an independent predictor of greater BCVA gain (β = -0.27; 95% CI -0.42 to -0.12; p = 0.0008). Eyes with complete PVD required more injections (p = 0.046). SRF and foveal-thickness reductions occurred across groups, whereas IRF changes were similar. Conclusions: Ultrasonography-defined PVD status differs markedly between nAMD and healthy eyes and independently influences neovascular phenotype and functional response to anti-VEGF therapy. These findings underscore the physiological importance of the vitreoretinal interface and support the use of ocular ultrasonography as an adjunct tool for assessing global vitreous status in selected nAMD settings.},
}

@article {pmid41516080,
year = {2025},
author = {Bhandari, SK and Lee, S and Kim, HJ},
title = {Integrative Landscape of Dry AMD Pathogenesis, Models, and Emerging Therapeutic Strategies.},
journal = {International journal of molecular sciences},
volume = {27},
number = {1},
pages = {},
doi = {10.3390/ijms27010202},
pmid = {41516080},
issn = {1422-0067},
support = {20230632//the Bisa Research Grant of Keimyung University/ ; },
mesh = {Humans ; Animals ; *Geographic Atrophy/pathology/metabolism/drug therapy/etiology/therapy ; Disease Models, Animal ; *Macular Degeneration/pathology/metabolism/etiology/drug therapy ; Oxidative Stress ; Mitochondria/metabolism ; },
abstract = {Dry age-related macular degeneration (AMD) is the leading cause of central vision loss among the elderly, yet no curative treatment exists. While exudative AMD can be managed with anti-vascular endothelial growth factor (VEGF) therapy, dry AMD-accounting for more than 85% of cases-progresses insidiously from drusen accumulation to geographic atrophy (GA). Although the recent U.S. Food and Drug Administration (FDA) approvals of pegcetacoplan and avacincaptad pegol represent major milestones, their therapeutic effects remain modest. This review provides an integrated overview of the molecular and cellular mechanisms underlying dry AMD, highlighting key pathogenic pathways involving oxidative stress, lipid dysregulation, complement activation, mitochondrial impairment, and RPE-specific bisretinoid lipofuscin accumulation. We further summarize mechanistic mouse models that replicate these pathological processes and discuss how each model contributes to understanding the disease. Finally, we review current and emerging therapeutic strategies-including complement inhibitors, visual cycle modulators, and mitochondrial-protective approaches-and outline future directions for translational research. Collectively, this review synthesizes mechanistic insights, disease models, and therapeutic innovation to support the development of targeted and stage-specific interventions for dry AMD.},
}

Humans
Animals
*Geographic Atrophy/pathology/metabolism/drug therapy/etiology/therapy
Disease Models, Animal
*Macular Degeneration/pathology/metabolism/etiology/drug therapy
Oxidative Stress
Mitochondria/metabolism

@article {pmid41515537,
year = {2025},
author = {Desmettre, T and Ledesma-Gil, G and Paques, M},
title = {Diagnostic Performance of Ring Aperture Retro Mode Imaging for Detecting Pigment Migration in Age-Related Macular Degeneration.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {1},
pages = {},
doi = {10.3390/diagnostics16010042},
pmid = {41515537},
issn = {2075-4418},
abstract = {Background/Objectives: Pigment migration is a key biomarker of progression in age-related macular degeneration (AMD). This study assessed the diagnostic performance of ring aperture Retro mode (RAR) imaging for detecting pigment migration and compared its performance with established multimodal imaging techniques. Methods: This retrospective study included 80 eyes from 61 consecutive patients with AMD who underwent multimodal imaging with color fundus images (CFIs), fundus autofluorescence (FAF), RAR imaging (Mirante, NIDEK), and en face optical coherence tomography (OCT) with B-scans (Cirrus HD-OCT 5000, Zeiss). Two independent retina specialists graded the AMD stage and the presence of pigment migration across modalities. Sensitivity and positive predictive value (PPV) of RAR were calculated using en face OCT as the reference standard. Results: RAR demonstrated high diagnostic performance, with a sensitivity of 94.7% and a PPV of 93.4% relative to en face OCT. RAR frequently identified pigment migration that was not visible on CFI or FAF, particularly in early AMD and in eyes with media opacity. Distinct morphologic patterns-including hyperreflective foci, thickened retinal pigment epithelium, refractile drusen, and cuticular drusen-were consistently identifiable on RAR. In four eyes with geographic atrophy, RAR detected perifoveal pigment redistribution at least six months before foveal involvement was confirmed by OCT and FAF. Conclusions: RAR imaging is a rapid, sensitive, and clinically practical technique for detecting pigment migration in AMD. By complementing en face OCT and enhancing visualization in cases where standard imaging is limited, RAR may strengthen early disease surveillance, support prognostic assessment, and improve multimodal diagnostic workflows in routine practice.},
}

@article {pmid41514281,
year = {2026},
author = {Almansa-García, AC and Armento, A and Cao, B and Petremann-Dumé, AS and Salmaso, S and Caliceti, P and Henes, C and Bolz, S and Kilger, E and Süsskind, D and Ueffing, M and Arango-Gonzalez, B},
title = {Safety and neuroprotective efficacy of the VCP inhibitor ML240 in large-animal and human retinal explants: a preclinical ex vivo study.},
journal = {BMC medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12916-025-04610-0},
pmid = {41514281},
issn = {1741-7015},
support = {AR1432/2-1//Deutsche Forschungsgemeinschaft/ ; },
abstract = {BACKGROUND: Retinal degenerative diseases represent a complex global health problem due to their significant impact on patients' daily lives and their highly heterogeneous pathogenesis, which challenges therapeutic development. Despite this complexity, many diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), share common features, including disrupted proteostasis, oxidative stress, and inflammatory responses, eventually leading to photoreceptor (PR) degeneration and vision loss. The inhibition of valosin-containing protein (VCP) has emerged as a promising mutation-independent therapeutic strategy for RP. However, clinical translation requires rigorous validation in models that closely reflect human retinal physiology.

METHODS: Organotypic retinal explants from porcine, macaque, and human donors were placed in an in vitro culture setup and treated with ML240, a selective VCP inhibitor, delivered either as a free compound or encapsulated in mPEG5kDa-cholane. Photoreceptor survival was assessed via TUNEL assay, outer nuclear layer (ONL) row quantification, and immunostaining. Retinal inflammation was evaluated by microglial staining. A dose-response study was performed to determine safety margins across species, and additional retinal markers were used to assess the preservation of non-photoreceptor retinal cell populations.

RESULTS: Porcine retinal explants exhibited progressive photoreceptor degeneration under ex vivo conditions. Treatment with ML240, particularly when formulated with mPEG5kDa-cholane, significantly reduced photoreceptor cell death and microglial activation. Macaque and human explants exhibited minimal to no signs of degeneration. Treatment did not affect morphological or histological features of the explant, demonstrating the safety of ML240 in the primate retina.

CONCLUSIONS: VCP inhibition via ML240 demonstrates an uncompromised safety profile in porcine, macaque, and human retinal explants. In addition, the neuroprotective activity of ML240 was evident in porcine tissue. Formulation with mPEG5kDa-cholane enhances the overall performance of the compound, supporting its use for future clinical application as a mutation-independent therapeutic approach for retinal degenerative diseases.},
}

@article {pmid41513975,
year = {2026},
author = {Cozzi, M and Airaldi, M and Barbieri, L and Sadda, SR and Staurenghi, G and Corvi, F},
title = {The impact of macular neovascularization development on geographic atrophy progression.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41513975},
issn = {1435-702X},
}

@article {pmid41513729,
year = {2026},
author = {Song, JR and Park, UC and Lee, CS and Cho, JJ and Kim, JY and Baek, SC and Jeong, A and Sharma, A and Kim, JH and Sagong, M and Woo, SJ and , },
title = {Real-world outcomes of ranibizumab biosimilars in various retinal diseases: a Korean multi-center experience-ROSE Korea Study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-34325-4},
pmid = {41513729},
issn = {2045-2322},
support = {RS-2024-00512384//Ministry of Health and Welfare/ ; },
abstract = {This study aims to investigate efficacy and safety of ranibizumab biosimilars (Amelivu[®] and LucenBS[®]) across retinal diseases in Korean clinical practice. This retrospective, multicenter study enrolled 1153 eyes from 1075 patients across five centers in South Korea between May 2022 and October 2024. Patients received intravitreal ranibizumab biosimilars for neovascular age-related macular degeneration, retinal vein occlusion with macular edema, diabetic macular edema, and other retinal diseases. Treatment-naïve eyes comprised 408 cases (35.4%), while 745 eyes (64.6%) had prior anti-VEGF treatment. Amelivu was administered to 1007 eyes with 3.1 ± 1.9 injections over 10.2 ± 6.1 months; LucenBS to 146 eyes with 3.1 ± 2.0 injections over 12.0 ± 4.9 months. Amelivu demonstrated significant BCVA(logMAR) improvements from baseline (0.63 ± 0.62) to 12 months (0.55 ± 0.61, P < 0.01). LucenBS maintained logMAR VA from 0.64 ± 0.63 to 0.63 ± 0.68 at 12 months (P = 0.40). Both biosimilars achieved significant CMT reductions through 12 months: Amelivu from 398.0 ± 169.4 μm to 323.0 ± 128.8 μm (P < 0.01); LucenBS from 368.7 ± 172.0 μm to 306.0 ± 144.1 μm (P < 0.01). Treatment-naïve eyes showed superior CMT reduction (111.8 μm) compared to previously treated eyes (53.5 μm). Only one injection-related adverse event occurred: asymptomatic anterior chamber cells in the Amelivu group, resolving with topical treatment. Ranibizumab biosimilars demonstrated visual stabilization and significant anatomical improvements across retinal diseases with excellent safety profiles.},
}

@article {pmid41513432,
year = {2026},
author = {Zhou, J and He, Y and Wang, J and Wu, H and Huang, X and Cao, J and Tham, YC and Zhang, C and Cheng, CY and Ye, J},
title = {Exposure-wide approaches identifying modifiable factors for age-related macular degeneration.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328446},
pmid = {41513432},
issn = {1468-2079},
abstract = {PURPOSE: The present study aimed to systematically investigate modifiable factors for age-related macular degeneration (AMD) using novel exposure-wide strategies in a large cohort, and then assess the preventability of AMD.

METHODS: Using data from the UK Biobank (UKB), a total of 331 modifiable factors from seven categories were included. Exposures were first screened using Cox proportional hazards models with each examined individually, and associated exposures were then tested in a mutually adjusted model for final validation. We calculated joint effect scores by combining validated exposures based on the category and tested the joint associations with AMD. We eventually estimated population attributable fraction to assess the overall preventability of AMD.

RESULTS: A total of 478 867 UKB participants were included. After a median of 13.63 years of follow-up, 10 903 (2.28%) were diagnosed with incident AMD. Among all 331 modifiable factors, 177 passed the exposure-wide association scan, with 34 exposures remaining statistically significant after mutual adjustment, distributed in 5 categories. Joint effects of these categories were significantly associated with AMD even among populations with higher AMD Polygenic Risk Score. Overall, we estimated that 30.4%-45.1% of AMD cases could be prevented by intervening in these factors.

CONCLUSIONS: Modifiable factors across multiple categories are associated with AMD, and active interventions targeting these factors can reduce AMD incidence by 30.4%-45.1%. This study also underscores the need for a systematic approach in uncovering modifiable factors and providing population-level knowledge basis for disease prevention.},
}

@article {pmid41517652,
year = {2022},
author = {Ledesma-Gil, G and Otero-Marquez, O and Alauddin, S and Tong, Y and Tai, K and Lloyd, H and Koci, M and Scolaro, M and Pillai, C and Ye, C and Govindaiah, A and Bhuiyan, A and Dhamoon, MS and Deobhakta, A and Lema, G and Narula, J and Rosen, RB and Yannuzzi, LA and Freund, KB and Smith, RT},
title = {Subretinal drusenoid deposits are strongly associated with coexistent high-risk vascular diseases.},
journal = {BMJ open ophthalmology},
volume = {7},
number = {1},
pages = {},
doi = {10.1136/bmjophth-2022-001154},
pmid = {41517652},
issn = {2397-3269},
abstract = {BACKGROUND/AIMS: Demonstrate that subretinal drusenoid deposits (SDDs) in age-related macular degeneration (AMD) are linked to coexistent high-risk vascular diseases (HRVDs).

METHODS: Cross-sectional study. Two hundred AMD subjects (aged 51-100 years; 121 women, 79 men) were recruited. Spectral domain optical coherence tomography, autofluorescence and near-infrared reflectance imaging, and lipid profiles were obtained. Subjects were assigned by health history questionnaires into those with or without HRVDs, defined as: cardiac valve defect (eg, aortic stenosis), myocardial defect (eg, myocardial infarction) and stroke/transient ischaemic attack. Masked readers assigned subjects into two groups: SDD (with or without drusen) and drusen (only). Univariate testing was performed by χ[2] test. We built multivariate regression models to test relationships of coexistent HRVD to SDD status, lipid levels and other covariates.

RESULTS: The prevalence of HRVD was 41.2% (40/97) and 6.8% (7/103) in the SDD and non-SDD groups, respectively (correlation of SDD with HRVD, p=9×10[-9], OR 9.62, 95% CI 4.04 to 22.91). Multivariate regressions: only SDDs and high-density lipoprotein (HDL) in the first two HDL quartiles remained significant for HRVD (p=9.8×10[-5], 0.021, respectively). Multivariate regression model: SDDs and an HDL in Q1 or Q2 identified the presence of HRVD with the accuracy of 78.5%, 95% CI 72.2% to 84.0%.

CONCLUSIONS: High-risk cardiovascular and neurovascular diseases were accurately identified in an AMD cohort from SDDs and HDL levels. The SDDs may be related to inadequate ocular perfusion resulting from the systemic vasculopathies. Further research with this paradigm is warranted and might reduce mortality and morbidity from vascular disease.},
}

@article {pmid41512983,
year = {2026},
author = {Lishinsky-Fischer, N and Gharra, S and Nitzan, I and Chowers, I and Levy, J},
title = {Reduced Risk of Non-Neovascular AMD in Cancer Patients Treated with Immune Checkpoint Inhibitors: A Propensity-Matched Cohort Study.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.12.035},
pmid = {41512983},
issn = {1879-1891},
abstract = {PURPOSE: To evaluate whether immune checkpoint inhibitors (ICIs), which modulate T-cell activity in cancer therapy, influence the risk of developing age-related macular degeneration (AMD).

DESIGN: Retrospective cohort study.

PARTICIPANTS: Adults aged ≥60 years with a history of cancer, identified from the TriNetX Global Collaborative Network. Only patients who remained alive throughout the follow-up period were included.

METHODS: Two cohorts were constructed: patients who received ICIs and those who did not. Sub-analyses were conducted for patients with melanoma and for those with metastatic disease. Propensity score matching (1:1) was performed using demographic and clinical covariates. Kaplan-Meier estimates and Cox proportional hazards models assessed the association between ICI exposure and AMD incidence over 5 years.

MAIN OUTCOME MEASURES: Incidence of non-neovascular and neovascular AMD after ICI therapy.

RESULTS: After matching, 36,037 patients were included in each cohort. ICI-treated patients had a significantly lower risk of developing non-neovascular AMD (hazard ratio [HR], 0.77; 95% CI, [0.63, 0.93]; log-rank P = 0.0084) over a 5-year follow-up. No significant association was observed between ICI exposure and neovascular AMD. The protective association persisted in melanoma and metastatic subgroups.

CONCLUSIONS: In this large, multicenter cohort, ICI therapy was associated with a reduced risk of non-neovascular AMD in older adults with cancer. These findings suggest a potential protective role of T-cell modulation in AMD pathogenesis and highlight the need for further research into the retinal effects of ICIs.},
}

@article {pmid41512710,
year = {2026},
author = {Shanidze, NM and Agathos, CP and Ellmers, TJ and Young, WR},
title = {Links between central visual field loss and movement processing during walking.},
journal = {Gait & posture},
volume = {125},
number = {},
pages = {110095},
doi = {10.1016/j.gaitpost.2026.110095},
pmid = {41512710},
issn = {1879-2219},
abstract = {BACKGROUND: Central visual field loss (CFL) is the most common irreversible visual impairment in aging and is associated with higher fall risk and concerns about falling. This study explored the links between CFL severity, functional balance, and walking-related attentional processing implicated in reduced gait performance.

METHODS: In Study 1, 29 individuals with CFL and 29 age-matched controls completed the Timed Up and Go (TUG) test. In Study 2, 10 CFL participants and 10 controls performed the TUG while acceleration data were collected from head and trunk IMUs. For both studies, we assessed visual impairment severity (contrast sensitivity) and participants' attentional processing during walking (Gait-Specific Attentional Profile, G-SAP).

RESULTS: Both groups showed positive correlations between TUG duration and G-SAP subscales. G-SAP scores were lower in CFL participants with worse contrast sensitivity indicating reduced cognitive processing during walking. Worse contrast sensitivity was also associated with greater head and trunk acceleration and acceleration variability during walking, suggesting reduced gait stability. Higher rumination and conscious movement processing scores also correlated with improved segmental control in CFL.

SIGNIFICANCE: Increased cognitive processing of gait is associated with impaired functional balance. This association appears to be reversed in CFL, with severe visual deficit diverting cognitive resources from movement control. This altered strategy may prioritise the acquisition and processing of visuospatial information in CFL. The observed postural instability with increasing CFL severity and a lack of excessive cognitive involvement in movement control suggest heightened gait-specific attention could be leveraged for balance and gait training in CFL.},
}

@article {pmid41511370,
year = {2026},
author = {Park, S and Song, YS and Feng, X and Sorenson, CM and Sheibani, N},
title = {Caffeine Mitigates Adenosine-Mediated Angiogenic Properties of Choroidal Endothelial Cells Through Antagonism of A1 Adenosine Receptor and PI3K-AKT Axis.},
journal = {Cells},
volume = {15},
number = {1},
pages = {},
doi = {10.3390/cells15010087},
pmid = {41511370},
issn = {2073-4409},
support = {Unrestricted award to the Department of Ophthalmology and Visual Science//Research to Prevent Blindness/ ; Endoument Fund//Retina Research Foundation/ ; Research Award//Arthur and Nancy Nesbit AMD fund/ ; AMD Research Award//The Edward N. & Della L. Thome Memorial Foundation/ ; AMD Research Award//Carl Marshall Reeves & Mildred Almen Reeves Foundation/ ; AMD Research Award//Pat and Jay Smith AMD Innovation Fund/ ; P30 EY016665/EY/NEI NIH HHS/United States ; EY034646/EY/NEI NIH HHS/United States ; EY030076/EY/NEI NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; },
mesh = {*Endothelial Cells/drug effects/metabolism/pathology ; *Caffeine/pharmacology ; Animals ; *Choroid/pathology/blood supply ; Humans ; *Phosphatidylinositol 3-Kinases/metabolism ; *Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/drug effects ; *Choroidal Neovascularization/drug therapy/pathology/metabolism ; *Adenosine/metabolism/pharmacology ; *Receptor, Adenosine A1/metabolism ; Mice ; },
abstract = {Aging reduces the tissue regenerative capacity, promotes chronic inflammation, and contributes to neurodegenerative diseases, including age-related macular degeneration (AMD). AMD is a leading cause of vision loss in older adults and manifests as dry (atrophic) or wet (neovascular) disease. Although dry AMD is more prevalent, neovascular AMD (nAMD) causes the most severe vision impairment and remains a major public health burden. Oxidative stress-mediated inflammation and dysfunction of retinal pigment epithelium (RPE) cells and choriocapillaris drive early AMD. Neovascular AMD is marked by pathologic choroidal neovascularization (CNV), driven largely by dysregulated VEGF signaling. Anti-VEGF therapies are the current standard of care for nAMD but require frequent intravitreal injections, carry procedure-related risks, and are ineffective in a substantial subset of patients, underscoring the need for new therapeutic approaches. Caffeine, a widely consumed and well-tolerated adenosine receptor antagonist, has emerging relevance in vascular regulation and inflammatory signaling. Extracellular ATP and its metabolites, including adenosine, accumulate under stress and act through purinergic receptors to influence angioinflammatory processes. We recently showed that systemic caffeine administration suppressed CNV in vivo, an effect partly reproduced by the adenosine receptor A2A antagonist Istradefylline. Here, we investigated the cell-autonomous effects of caffeine on mouse choroidal endothelial cells, focusing on its role as an adenosine receptor antagonist and its potential to inhibit pathological neovascularization.},
}

*Endothelial Cells/drug effects/metabolism/pathology
*Caffeine/pharmacology
Animals
*Choroid/pathology/blood supply
Humans
*Phosphatidylinositol 3-Kinases/metabolism
*Proto-Oncogene Proteins c-akt/metabolism
Signal Transduction/drug effects
*Choroidal Neovascularization/drug therapy/pathology/metabolism
*Adenosine/metabolism/pharmacology
*Receptor, Adenosine A1/metabolism
Mice

@article {pmid41510773,
year = {2026},
author = {Bazan, NG},
title = {Elovanoids: linking nutrition to neuroprotection.},
journal = {Current opinion in clinical nutrition and metabolic care},
volume = {},
number = {},
pages = {},
doi = {10.1097/MCO.0000000000001198},
pmid = {41510773},
issn = {1473-6519},
abstract = {PURPOSE OF REVIEW: Elovanoids are homeostatic lipid mediators derived from the very long-chain n-3 polyunsaturated fatty acids, which are in turn derived from docosahexaenoic acid (DHA). The aim of this review is to summarize the latest research on these lipid mediators.

RECENT FINDINGS: Elovanoids beneficially modulate thioredoxin reductase 1, a key component in the activation of the cellular glutathione antioxidant system. Elovanoids prevent oligomeric amyloid-beta-induced senescence and inflammaging in retinal pigment epithelium and other cells. Rod cells' ability to use DHA to produce elovanoid precursors is decreased in age-related macular degeneration, a disease that causes photoreceptor loss and blindness.

SUMMARY: Elovanoids are molecular guardians of nervous system integrity that introduce a new aspect of neuroprotective signaling by serving as an initial line of defense when neural cell homeostasis is jeopardized. Appropriate diet contributes to healthy aging by providing the precursor (DHA) that favors elovanoid-mediated neuroprotection in conditions including stroke, traumatic brain injury, macular degeneration, Alzheimer's, and Parkinson's.},
}

@article {pmid41510735,
year = {2026},
author = {Fnu, G and Bhatt, P and Gupta, SV and Sharma, P and Sutariya, V},
title = {Formulation Development and In vitro Characterization of Nanoparticles of Pazopanib for Wet Macular Degeneration.},
journal = {Current drug delivery},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115672018385478251124140833},
pmid = {41510735},
issn = {1875-5704},
abstract = {INTRODUCTION: One of the primary causes of severe vision loss globally is age-related macular degeneration (AMD), and the mainstay of therapies for neovascular diseases is intravenous administration of anti-VEGF (vascular endothelial growth factor) drugs. The goal of this research is to create an effective delivery of anti-VEGF drugs to overcome the challenges associated with current therapy and adverse effects arising from repetitive intravitreal injections.

METHODS: Pazopanib (PZ) nanoparticles (NPs) have been generated to deliver the anti-VEGF drug to the posterior segment of the eye over an extended period via intravitreal injection. They were subsequently investigated for physicochemical and in vitro studies.

RESULTS: The PZ NPs were found to be nano-sized with a particle size of 132.1 ± 1.4 nm and a PDI of 0.125 ± 0.023. The results showed that the zeta potential was -20.12 ± 2.7 mV and the entrapment efficiency was 33.9 ± 2.5%. Up to seven days of controlled drug release was observed in an in vitro drug release study. The PZ NPs were further assessed for cell cytotoxicity, cellular uptake, and anti- VEGF assays in in vitro cell culture investigations employing human retinal pigment epithelium cells (ARPE-19). In vitro cell culture tests revealed that, in comparison to the drug solution, the PZ NPs formulation was well taken up by the cells and less cytotoxic, as well as exhibited greater antiangiogenic efficacy by inhibiting VEGF expression for an extended period of time.

DISCUSSION: The NPs demonstrated sustained drug release, driven by their controlled degradation kinetics. Increased potential intensity enhanced electrostatic repulsion, thereby improving NP stability. The low entrapment efficiency of PZ in the NPs was likely due to drug diffusion during emulsification and poor compatibility with the hydrophilic polymer matrix. For in vitro studies, ARPE-19 cells were selected due to their retinal pigment epithelial (RPE)-like properties, making them suitable for AMD drug testing. Efficacy (ELISA) assessments revealed that NP formulations had a stronger inhibitory effect than free drug solutions.

CONCLUSION: The proposed PZ NPs were successfully developed, characterized, and demonstrated potential application in the treatment of AMD.},
}

@article {pmid41510605,
year = {2026},
author = {Ma, C and Su, J and Liu, J and Zhao, T and Li, X and Cai, S and Ji, X and Wu, J and Wang, L and Xu, D},
title = {Discovery of (3R,4R)-15: An Advanced Factor B Inhibitor Entering Phase 3 for Complement-Mediated Diseases.},
journal = {Journal of medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.1021/acs.jmedchem.5c03532},
pmid = {41510605},
issn = {1520-4804},
abstract = {The alternative pathway (AP) of the complement system plays a critical role in the pathogenesis of various human diseases, including age-related macular degeneration (AMD), paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and several glomerular diseases. Although the approved drug Iptacopan is available, it requires twice-daily oral dosing, resulting in suboptimal patient compliance. Using a scaffold-hopping strategy, we identified the clinical candidate (3R,4R)-15, which exhibits potent inhibitory activity against factor B (FB) and the AP, with IC50 values of 10.2 nM and 59.3 nM, respectively. Furthermore, this compound exhibits significantly improved pharmacokinetic properties, including an oral bioavailability of 69.2% in mice. Preliminary clinical studies indicate that (3R,4R)-15 has promising efficacy in patients with PNH. Its once-daily dosing regimen also offers the potential to markedly improve patient compliance. (3R,4R)-15 is currently in Phase 3 trials evaluating its efficacy for the treatment of PNH.},
}

@article {pmid41509480,
year = {2025},
author = {Alizadeh, AM and Lin, B and Seiler, M and Lyon, DC},
title = {Restoration of Higher-Order Cortical Processing in Rat V2 by Retinal Sheet Transplants in Degenerated Rats.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.21.690582},
pmid = {41509480},
issn = {2692-8205},
abstract = {Age-related macular degeneration (AMD) is a leading cause of central vision loss, and effective treatment options are limited once photoreceptors and the retinal pigment epithelium (RPE) are lost. In advanced stages, vision restoration requires strategies that replace or bypass degenerated retinal circuitry. Retinal sheet transplantation using fetal neural retinal tissue has emerged as a promising intervention, demonstrating long-term survival, integration with the host retina, and partial restoration of light-driven responses. We previously showed that such transplants can restore fundamental visual response properties in the primary visual cortex (V1) of rapidly degenerating rats. However, it remains unclear whether restored retinal input can support higher-order cortical computations that depend on the integration of classical and extra-classical receptive field mechanisms. In this study, we extend this investigation by evaluating whether fetal retinal sheet transplants can restore extra-classical surround modulation in neurons of higher visual areas (V2). Fetal retinal sheets (E18-E19) derived from donor rats were transplanted into one eye of Rho-S334ter line-3 rats at ages P41-P78, when rod degeneration is nearly complete and cones are largely nonfunctional. Animals were assessed 2.2-9.3 months post-surgery using in vivo extracellular single-unit recordings from V2, optokinetic testing, OCT imaging, and histology. Control groups included normal-vision rats, age-matched degenerated rats (AMC), and sham-operated line-3 rats. Transplants survived long term, developed laminated and rosetted photoreceptor structures, and integrated with the host retina. Optokinetic testing revealed significant improvement in spatial acuity in transplanted eyes compared with degenerated controls beginning at three months post-surgery. Transplanted rats exhibited a markedly higher proportion of visually responsive V2 neurons than degenerated animals (21.0% vs. 8.2%). They also showed significantly shorter response latencies and larger visually evoked response amplitudes, indicating improved transmission of retinal signals to the cortex. To quantify surround suppression, neurons were tested with sinusoidal gratings confined to the classical receptive field and gratings extended to full-field size. Transplanted rats displayed robust surround suppression properties similar to normal controls, including significantly reduced firing rates and narrower tuning under full-field conditions. A Support Vector Machine (SVM) classifier trained on net responses to CRF and FF stimulus sizes reliably distinguished control and transplanted neurons from degenerated ones but could not separate control from transplant, further indicating similar response properties in these two groups. These findings provide the first demonstration that retinal sheet transplants restore not only basic visual responses but also higher-order cortical mechanisms involving extra-classical surround suppression. This recovery of surround suppression in V2 suggests that transplanted retinal tissue can re-establish functionally meaningful circuits capable of supporting complex visual processing. The results underscore the therapeutic potential of retinal sheet transplantation for advanced retinal degenerative disease and provide the first evidence of surround suppression in the rat V2.},
}

@article {pmid41509408,
year = {2025},
author = {Chacin Ruiz, EA and Swindle-Reilly, KE and Ford Versypt, AN},
title = {Modeling and Design of Multi-layered Cylindrical Microcapsules for Intravitreal Controlled Release.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.29.696951},
pmid = {41509408},
issn = {2692-8205},
abstract = {Chronic diseases often require repeated oral or local administration, which can compromise patient compliance. In wet age-related macular degeneration (AMD), current therapies rely on intravitreal injections of anti-vascular endothelial growth factor agents every four to six weeks to maintain therapeutic drug levels. Controlled-release drug delivery systems offer a promising alternative by reducing injection frequency and extending drug release. In this study, we developed a continuum diffusion model to describe drug transport through porous polymeric microcapsules, implemented using the finite element method in COMSOL Multiphysics. The case study focused on cylindrical microcapsules fabricated with either a single polycaprolactone (PCL) layer or a bi-layered chitosan-PCL structure, tested at two capsule sizes and three salt leaching concentrations. Bovine serum albumin and bevacizumab were used as model drugs. Parameter estimation was performed using published release data, with a progressive fitting strategy that carried forward parameters from simpler systems into more complex designs. The model reproduced experimental release profiles across formulations and identified key transport parameters governing release dynamics, including porosity, tortuosity, and mass transfer rates. Design exploration revealed that polymer thickness was the dominant factor controlling release, while addition of the chitosan layer moderated the initial burst and extended therapeutic delivery. This framework demonstrates how computational modeling can reduce experimental burden, guide design optimization, and support the development of long-acting intravitreal drug delivery systems to treat wet AMD by linking drug release kinetics to design variables.},
}

@article {pmid41508137,
year = {2026},
author = {Rubio, AP and Dunn, J and Borthwick, J and Saunders, S and Tochel, C and Anderson, H and Coull, L and Javidi, M and Cloete, H and McTrusty, A and Penny, J and MacGillivray, T and Tatham, AJ and Jackson, T and Porteous, C and Strang, N and Dhillon, B and Bernabeu, MO},
title = {Beyond the dataset: integrating public voices in data science.},
journal = {Research involvement and engagement},
volume = {12},
number = {1},
pages = {2},
pmid = {41508137},
issn = {2056-7529},
support = {TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; TCS/24/15/CSO_/Chief Scientist Office/United Kingdom ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; 07425//NHS Lothian Charity/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; RESSTR2301//Fight for Sight UK/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; GA-02328 and GA-02771//RS Macdonald Charitable Trust/ ; },
abstract = {The digitalisation of health data has helped drive initiatives like the Scottish Collaborative Optometry-Ophthalmology Network eResearch (SCONe), which links retinal images from community optometry practices with other routinely collected health data to enhance disease detection. As data-driven approaches expand throughout the healthcare system, patient and public involvement and engagement (PPIE) is increasingly recognised as essential for improving the quality, relevance, and acceptability of health research. However, despite growing endorsement, challenges remain, including inconsistent terminology, varying levels of involvement, limited implementation guidance, and a lack of evidence on its impact. These challenges are even more pronounced in data science, particularly within large-scale research, where PPIE is often underreported, leaving the field without a clear framework for meaningful implementation. This article offers a reflective account of the challenges and barriers encountered by SCONe in developing a PPIE strategy. By documenting this process, it provides insights into the complexities of implementing PPIE in large research consortia and offers practical guidance for future initiatives seeking to enhance the impact and relevance of public partnerships in large scale data science research.},
}

@article {pmid41504873,
year = {2026},
author = {Stettler, I and Romano, F and Nigalye, A and Lains, I and Choi, H and Ding, X and Bennett, CF and Overbey, KM and Ploumi, I and Garg, I and Katz, R and Kasetty, M and Vingopoulos, F and Vavvas, DG and Miller, JW and Husain, D and Miller, JB},
title = {Assessing the role of macular pigment optical volume in non-neovascular age-related macular degeneration: associations with rod-mediated dark adaptation and disease progression.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41504873},
issn = {1435-702X},
abstract = {PURPOSE: To characterize macular pigment optical volume (MPOV) across non-neovascular age-related macular degeneration (AMD) stages and in healthy controls, and to explore its associations with dark adaptation (DA) time and long-term AMD progression.

DESIGN: Cross-sectional and longitudinal observation study including patients with non-neovascular AMD (early, intermediate, advanced) per Beckman classification and age-similar controls with no retinal disease. All eyes had good-quality dual-wavelength autofluorescence imaging (Spectralis Investigational MPOD Module).

METHODS: DA was assessed using the AdaptDx[®] extended protocol (LumiThera, Poulsbo, WA). MPOV was calculated for three concentric circles centered on the fovea at radii of 1°, 2°, and 6°. AMD progression was determined through consultation of follow-up clinical and imaging data. Mixed-effects linear regression models evaluated baseline differences between AMD and control eyes, and across non-neovascular AMD stages. Progression risk was assessed using mixed-effectsCox proportional hazards models adjusted for age, AREDS2 use, lens opacities, and fellow eye status.

RESULTS: Our analysis included 110 AMD eyes (58 patients; median age 72, 56.9% female) and 51 control eyes (26 patients; median age 64, 53.9% female). AMD eyes had significantly higher MPOV than controls when calculated at all eccentricities (1, 2, and 6°, all p<0.01). In controls, higher MPOV at all eccentricities was associated with shorter DA time (p<0.05) - a relationship not observed in AMD eyes. Of 108 AMD eyes with follow-up (median, 53.1 months), 24 eyes (22.9%) progressed to a more advanced stage. Higher MPOV values at all eccentricities were independently associated with increased progression risk (all p<0.05) CONCLUSIONS: AMD eyes show greater MPOV values than controls, especially in intermediate stages. While MPOV correlated with better DA performance in healthy eyes, this relationship was absent in AMD, suggesting a more complex interaction in diseased retina.},
}

@article {pmid41503694,
year = {2026},
author = {Hua, Z and Zhu, Q and Yang, J and Tang, M and Yin, J and Zhan, D},
title = {Mendelian Randomization Study of Age-Related Macular Degeneration and Inflammatory Bowel Disease.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/02713683.2025.2602902},
pmid = {41503694},
issn = {1460-2202},
abstract = {PURPOSE: To investigate the causal relationship between age-related macular degeneration (AMD) and inflammatory bowel disease (IBD) by Mendelian randomization (MR) analysis.

METHODS: The single nucleotide polymorphism data of IBD and AMD were obtained from the Integrative Epidemiology Unit (IEU) Open genome-wide association study database. MR analysis contained MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode. Sensitivity analysis was executed to ensure the reliability of results, containing heterogeneity test, horizontal pleiotropy test, and leave-one-out analysis. Multivariable Mendelian randomization analysis was carried out to investigate potential confounding factors such as C-reactive protein, smoking, vitamin D deficiency. Genes corresponding to the instrumental variables (IVs) and functional enrichment analysis were executed.

RESULTS: MR analysis showed a positive correlation between IBD and AMD (P < 0.05, OR > 1). Sensitivity analyses also did not reveal heterogeneity and horizontal pleiotropy. C-reactive protein, smoking, and vitamin D deficiency had no significant effect on AMD (P > 0.05). Genes corresponding to IVs were mainly associated with monocyte differentiation, cytokine receptor activity, etc., and act on signaling pathways such as Th17 cell differentiation, and there was a complex network of molecular-cell regulation.

CONCLUSION: Our study explored and demonstrated the causal relationship between IBD and AMD through MR analysis, which provided an important reference and direction for future research and treatment related to AMD.},
}

@article {pmid41502314,
year = {2026},
author = {Lee, S and Choi, J and Yu, SY and Kim, K},
title = {Quantitative optical coherence tomography angiography biomarkers Following a Switch to Brolucizumab in Neovascular age-related macular degeneration.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2025.0144},
pmid = {41502314},
issn = {2092-9382},
abstract = {PURPOSE: To evaluate functional and anatomical outcomes, including vessel morphology parameters on swept-source optical coherence tomography angiography (SS-OCTA), in eyes with neovascular age-related macular degeneration (nAMD) switched to brolucizumab.

METHODS: This retrospective study included 37 eyes with nAMD that were switched from other anti-vascular endothelial growth factor (VEGF) agents to intravitreal brolucizumab. Best-corrected visual acuity (BCVA), injection intervals, central subfield thickness (CST), pigment epithelial detachment (PED) and presence of retinal fluid were compared between baseline and 12 months post-switch. SS-OCTA images were analyzed to quantify macular neovascularization (MNV) area, vessel density, fractal dimension (FD), and lacunarity.

RESULTS: Switching to brolucizumab significantly extended injection intervals and reduced CST, PED height and retinal fluid, while maintaining BCVA at 12 months. Quantitative OCTA analysis showed reductions in MNV area and FD following the switch. When compared with the preceding 12 months of other anti-VEGF therapy, FD still showed a significant reduction after brolucizumab treatment (p = 0.019). Intraocular inflammation occurred in 1 eye and resolved with topical corticosteroids.

CONCLUSIONS: Intravitreal brolucizumab demonstrated favorable anatomical improvements and maintained visual outcomes over 12 months. Quantitative OCTA biomarkers, particularly FD, may serve as imaging indicators of disease activity and treatment response in eyes with nAMD undergoing a therapy switch.},
}

@article {pmid41501830,
year = {2026},
author = {Fang, J and Huang, Y and Li, B and Du, Y},
title = {Role and regulation of kinases in age-related macular degeneration.},
journal = {Journal of translational medicine},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12967-025-07669-8},
pmid = {41501830},
issn = {1479-5876},
}

@article {pmid41501669,
year = {2026},
author = {Luo, Y and Xia, Y and Gong, X and Hao, M and Wei, Q and Liao, L},
title = {GLP-1 receptor agonists in eye disease: a comprehensive review of current research and future potential.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {12},
pmid = {41501669},
issn = {1471-2415},
abstract = {OBJECTIVE: To synthesize the current preclinical and clinical evidence on the utility and potential mechanisms of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as a therapeutic strategy for major ophthalmic diseases, including diabetic retinopathy, glaucoma, and age-related macular degeneration.

METHODS: A comprehensive literature search was conducted to synthesize the current preclinical and clinical evidence. Electronic databases including PubMed, Embase, and Web of Science were searched from inception until August 2025 using keywords such as “GLP-1 receptor agonist,” “diabetic retinopathy,” “glaucoma,” “age-related macular degeneration,” “ocular disease,” and “neuroprotection.” The search focused on identifying preclinical studies, large-scale retrospective cohort studies, and post-hoc analyses of major clinical trials that evaluated the utility and potential mechanisms of GLP-1RAs in ophthalmic diseases. Studies were screened for relevance based on title and abstract, and full texts were retrieved for detailed assessment.

RESULTS: Despite heterogeneity in study designs and populations, a largely consistent association was found between GLP-1RA use and a reduced incidence of glaucoma. For diabetic retinopathy, the evidence was nuanced, indicating potential long-term neurovascular protection but also a risk of transient early worsening. For age-related macular degeneration, findings were dichotomous, suggesting a protective effect against non-exudative forms but a potential increased risk for neovascular disease.

CONCLUSION: GLP-1RAs show significant promise as a potential disease-modifying therapy for neurodegenerative and inflammatory eye diseases, acting through both systemic metabolic improvements and direct ocular mechanisms, representing a paradigm shift beyond their metabolic indications.},
}

@article {pmid41500399,
year = {2026},
author = {Wang, Y and Liu, X and Zeng, S and Yang, W and Cao, F and Hou, S},
title = {The Role and Mechanism of Post-Translational Modifications (PTMs) in Immune-Related Eye Diseases.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110851},
doi = {10.1016/j.exer.2026.110851},
pmid = {41500399},
issn = {1096-0007},
abstract = {Post-translational modifications (PTMs) encompass the spectrum of chemical covalent alterations that proteins undergo after being synthesized from mRNA. These modifications typically involve the covalent bonding of chemical groups or small protein molecules to the amino acid backbones or side chains. Currently, over 650 types of PTMs have been identified, including significant ones such as phosphorylation, ubiquitination, SUMOylation, methylation, acetylation, glycosylation, among other novel varieties like lactylation. However, a systematic review of PTMs associated with immune-mediated ocular diseases remains conspicuously absent in current literature. To fully understand the role of PTM in immune eye diseases, this review systematically introduces the regulatory mechanisms and functions of several important PTMs. Furthermore, this review also encapsulates the mechanisms of PTMs in several pivotal immune-related ocular conditions, specifically uveitis, age-related macular degeneration (AMD), dry eye disease (DED), and diabetic retinopathy (DR). By integrating current evidence, this work not only clarifies the pathogenic contributions of specific PTMs but also identifies their potential as therapeutic targets. Finally, we discuss future research directions and the challenges of translating PTM-based interventions into clinical practice for ocular immune disorders.},
}

@article {pmid41500346,
year = {2026},
author = {Cortivo, GD and Longo, C and Müller, B and Avesani, A and Pacchiana, R and Weller, M and Marino, V and Lytvynchuk, L and Stieger, K and Dell'Orco, D},
title = {Protein delivery to the eye: assessing therapeutic potential across inner and outer retina.},
journal = {International journal of pharmaceutics},
volume = {},
number = {},
pages = {126568},
doi = {10.1016/j.ijpharm.2026.126568},
pmid = {41500346},
issn = {1873-3476},
abstract = {Protein-based therapeutics represent a promising approach for treating diseases of the retina, yet effective delivery systems and translational models remain limited. We developed a robust ex vivo framework utilizing murine and porcine retinal explants to investigate protein delivery mechanisms for both peripheral and central retinal regions. Using guanylate cyclase-activating protein-1 (GCAP1) as a retina-specific model protein and mCardinal2 as a non-retina-specific control, we demonstrated spontaneous protein internalization and accumulation in photoreceptors and ganglion cells following single-dose administration. In murine explants, myristoylated GCAP1 exhibited sustained retention and appropriate subcellular targeting in rod photoreceptors over 96 h without inducing tissue damage. Porcine explants, which better recapitulate human macular architecture, revealed differential protein trafficking dependent on post-translational modifications. Retinal tissue showed preferential uptake and retention of retina-specific proteins over foreign proteins, suggesting sophisticated protein-specific recognition mechanisms. Liposomal encapsulation enhanced initial uptake of non-retina-specific proteins but did not improve long-term retention. This experimental platform provides a valuable tool for screening protein therapeutics, optimizing delivery formulations, and investigating protein-selective cellular uptake mechanisms, with direct implications for developing treatments for inherited retinal degenerations, age-related macular degeneration, and optic nerve pathologies.},
}

@article {pmid41499990,
year = {2026},
author = {Chen, C and Wang, C and Li, H and Wang, T and Jiao, X},
title = {Sweet poison for the eyes: High-Fructose diets as drivers of metabolic disruption and ocular diseases - Insights and therapeutic horizons.},
journal = {Experimental eye research},
volume = {264},
number = {},
pages = {110852},
doi = {10.1016/j.exer.2026.110852},
pmid = {41499990},
issn = {1096-0007},
abstract = {Excess consumption of added sugars, commonly delivered through sucrose and high-fructose corn syrup, has increased in parallel with obesity, metabolic syndrome, and type 2 diabetes. These systemic metabolic disturbances are consistently associated with a range of ocular conditions. However, whether high-fructose intake exerts independent and fructose-specific effects on ocular tissues remains uncertain, because most human evidence is indirect, often mediated through metabolic syndrome phenotypes, and frequently confounded by mixed dietary exposures and total energy intake. This review synthesizes mechanistic pathways that are plausibly enriched by fructose biology, including hepatic fructose metabolism with ATP depletion and uric acid generation, oxidative and inflammatory signaling, altered lipid handling, and gut barrier and microbiome perturbations. We evaluate how these systemic changes may intersect with ocular surface homeostasis, retinal neurovascular integrity, intraocular pressure regulation, and choroidal and macular vulnerability. Across dry eye disease, diabetic retinopathy, glaucoma-related outcomes, age-related macular degeneration and choroidal neovascular responses, and cataract, we distinguish fructose-specific exposure studies from metabolic syndrome only and mixed diet reports, and we emphasize limitations related to exposure definition, replication, and translation to humans. Overall, current evidence supports the view that excess fructose may amplify ocular susceptibility in metabolically stressed states, but direct causal links in humans remain preliminary. We conclude by outlining methodological priorities and testable study designs needed to clarify fructose-specific contributions to ocular disease risk. Some experimental findings, particularly those related to ocular-surface responses, originate from single research groups and require independent replication, underscoring that current evidence remains preliminary and hypothesis-generating.},
}

@article {pmid41499325,
year = {2026},
author = {Karam, M and Baeshen, M and Alfuzaie, R and Mohammad, M and Alshatti, A and Samet, A and Paez-Escamilla, M and Sun, V},
title = {Efficacy of Faricimab in Neovascular Age-Related Macular Degeneration: A Single-Arm Systematic Review and Meta-Analysis.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1-27},
doi = {10.1159/000550348},
pmid = {41499325},
issn = {1423-0259},
abstract = {PURPOSE: To evaluate the efficacy of faricimab in neovascular age-related macular degeneration (nAMD).

METHODS: This systematic review and meta-analysis was performed according to the PRISMA guidelines to identify studies assessing faricimab in nAMD. Primary outcomes included visual acuity, central macular thickness (CMT), and dry macula rate. Secondary outcomes included macular status, central choroidal thickness (CCT), and complications. A random-effects model was used to calculate pooled mean with 95% confidence intervals.

RESULTS: Out of the 365 studies identified, 21 studies were included, comprising a total sample size of 1864 eyes of 1791 patients. Post-operatively, there was a statistically significant improvement in corrected distance visual acuity (CDVA) (SMD: -0.122, 95% P = 0.039) and CMT (SMD: -3.672, P = 0.010). Similarly, there was a significant improvement in the rate of dry macula at the final follow-up visit (event rate: 0.529; P < 0.05). For the secondary outcomes, there was a statistically significant improvement in CCT (SMD: -0.199, P = 0.026) and in the rate of macular exudates (0.452, P < 0.05), specifically intraretinal fluid (0.140, P < 0.05) and subretinal fluid (0.271, P < 0.05). Complications secondary to faricimab injections included hemorrhagic pigment epithelial detachment (PED) with a rate of 0.120 (P < 0.05) and retinal pigment epithelium (RPE) tear with a rate of 0.025 (P < 0.05).

CONCLUSIONS: The use of faricimab injection in patients with nAMD is safe and effective, resulting in significant improvements in a myriad of visual measures and OCT parameters.},
}

@article {pmid41497719,
year = {2025},
author = {Zhang, M and Wang, Y and Feng, L and Zhang, P and Li, Y and Chen, H},
title = {Massive Hemorrhage in PCV Is Associated With Lower-Than-Normal VEGF Level and Dramatically Elevated Inflammatory Cytokine Levels in Aqueous Mingxuan.},
journal = {Journal of ophthalmology},
volume = {2025},
number = {},
pages = {9272271},
pmid = {41497719},
issn = {2090-004X},
abstract = {PURPOSE: To compare the aqueous cytokine profile in polypoidal choroidal vasculopathy (PCV) with or without massive hemorrhage and typical neovascular age-related macular degeneration (nAMD).

METHODS: The present comparative study included 81 treatment-naïve eyes from 75 patients (PCV with massive hemorrhage 20 eyes, PCV without massive hemorrhage 19 eyes, typical nAMD 19 eyes, and cataract control 23 eyes). 10 cytokines (VEGF, IL-6, IL-8, MCP-1, ICAM-1, VCAM-1, IP-10, G-CSF, and IFN-γ, IL-10) in the aqueous humor were measured by cytometric bead array.

RESULTS: VEGF levels in PCV with massive hemorrhage (median 5.20 pg/mL) were significantly lower than that in PCV without massive hemorrhage (median 34.76 pg/mL, p = 0.003) and typical nAMD (median 43.88 pg/mL, p < 0.001). They were even lower than that in normal cataract controls (median 22.02 pg/mL, p = 0.037). Multiple inflammatory cytokines were dramatically elevated in PCV with massive hemorrhage. IL-6, IL-8, MCP-1, ICAM-1, and IP-10 levels were significantly higher in PCV with massive hemorrhage than that in the other three groups. VCAM-1 levels were significantly higher in PCV with massive hemorrhage than that in typical nAMD and in control. G-CSF and IFN-γ levels were significantly higher in PCV without massive hemorrhage than that in control. IL-10 levels were significantly higher in PCV with massive hemorrhage than that in typical nAMD.

CONCLUSIONS: This pilot study showed that PCV with massive hemorrhage had a lower-than-normal VEGF level in aqueous humor and inflammation may be actively involved in the pathogenesis of massive hemorrhage in PCV.},
}

@article {pmid41497650,
year = {2025},
author = {Pandala, N and De Melo Haefeli, L and Khan, A and Steffan, H and Miller, J and Stone, EM and Han, IC and Lavik, EB and Mullins, RF and Tucker, BA},
title = {Acriflavine delivery via Polyurethane nanocapsules to treat neovascular age-related macular degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.22.695712},
pmid = {41497650},
issn = {2692-8205},
abstract = {Choroidal neovascularization is a complication associated with retinal diseases such as age-related macular degeneration (AMD), a leading cause of vision loss in the developed world. Choroidal neovascular membrane (CNVM) refers to the abnormal growth of blood vessels in the retina which results in exudation and/or hemorrhage, leading to photoreceptor damage and vision loss. Currently first-line treatment for CNVM include intravitreal injections of vascular endothelial growth factor (VEGF)-binding antibodies that prevent the growth of these leaky blood vessels. Unfortunately, anti-VEGF drugs often require frequent injections, and prolonged VEGF inhibition has been associated with retinal atrophy and decreased long term effectiveness in some patients. This study presents the use of Acriflavine, a small molecule HIF1α inhibitor loaded polyurethane nanocapsules to treat CNVM in a rat model. Fourteen days following laser injury and intravitreal drug administration, CMVM size was significantly reduced in acriflavine nanocapsule and free acriflavine treated animals as compared to drug free controls. Moreover, acriflavine nanocapsules reduce CNVM incidence compared to drug free controls by approximately 25%. Among the different delivery routes tested, intravitreal delivery of acriflavine nanocapsules was found to be superior to subretinal and suprachoroidal delivery for reducing CNVM area without causing significant damage to the neural retina. This paper presents the synthesis, characterization and the effectiveness of the polyurethane based acriflavine delivery system in treating choroidal neovascularization.},
}

@article {pmid41497268,
year = {2026},
author = {Gong, X and Feng, J and Han, Y and Tang, G and Yin, Y and Li, J and Liu, Y and Zhang, J and Song, J and Bi, H},
title = {Research progress on glycolytic reprogramming in ophthalmic diseases.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e20478},
pmid = {41497268},
issn = {2167-8359},
mesh = {Humans ; *Glycolysis ; *Eye Diseases/metabolism ; Animals ; *Retina/metabolism ; Uveal Neoplasms/metabolism ; Energy Metabolism ; Uveal Melanoma ; Melanoma/metabolism ; Glaucoma/metabolism ; Cellular Reprogramming ; },
abstract = {The retina is one of the most energy-demanding tissues in the human body. Retinal energy metabolism is primarily dominated by aerobic glycolysis, with more than 80% of the glucose consumed being converted to lactic acid. As a highly energy-consuming tissue, the metabolic characteristics of the retina, especially aerobic glycolysis, are essential for maintaining retinal cell function during normal physiological processes. However, in disease states, this metabolic balance is disrupted, leading to a range of pathological changes. There is currently growing evidence that metabolic reprogramming is a pathological cause of diseases such as retinal degeneration, uveal melanoma, and glaucoma. This article reviews the mechanisms involved in metabolic reprogramming in ocular diseases and describes relevant therapeutic targets. Despite the many advances, the regulatory mechanisms of metabolic reprogramming in ophthalmic diseases still need to be thoroughly investigated, and new therapeutic strategies are expected to be developed based on this in the future.},
}

Humans
*Glycolysis
*Eye Diseases/metabolism
Animals
*Retina/metabolism
Uveal Neoplasms/metabolism
Energy Metabolism
Uveal Melanoma
Melanoma/metabolism
Glaucoma/metabolism
Cellular Reprogramming

@article {pmid41495013,
year = {2026},
author = {Li, H and Weiss, CE and Pandiyan, VP and Nanni, D and Liu, T and Kung, PW and Tan, B and Barathi, VA and Schmetterer, L and Sabesan, R and Ling, T},
title = {Optoretinography reveals rapid rod photoreceptor movement upon rhodopsin activation.},
journal = {Light, science & applications},
volume = {15},
number = {1},
pages = {58},
pmid = {41495013},
issn = {2047-7538},
support = {NRF-NRFF14-2022-0005//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; NRF-CRP24-2020-0001//National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore)/ ; Startup Grant//Nanyang Technological University (NTU)/ ; NMRC/CG/C010A/2017; MOH-001748-00//MOH | National Medical Research Council (NMRC)/ ; NMRC/CG/M010/2017/Pre-Clinical; NMRC/CG21APR1010-SAMURAI/Pre-Clinical Core Platform/2021_SERI//MOH | National Medical Research Council (NMRC)/ ; RS19/20; RG28/21//Ministry of Education - Singapore (MOE)/ ; I010/2024 [2082/44/2024]//Singapore Eye Research Institute (SERI)/ ; U01EY032055; EY029710//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; unrestricted grant//Research to Prevent Blindness (RPB)/ ; },
abstract = {Rod photoreceptors are essential for vision under dim light conditions and are highly vulnerable in retinal degenerative diseases. Here, we demonstrate that both human and rodent rods undergo a minute and rapid contraction of their outer segments upon photoisomerization, the first step of phototransduction. The contraction is explained as an electromechanical manifestation of the rod early receptor potential generated in the disk membranes, which is challenging to access in electrophysiology. The in vivo optical imaging of light-evoked electrical activity in rodent rods was facilitated by an ultrahigh-resolution point-scan optical coherence tomography (OCT) system, combined with an unsupervised learning approach to separate the light-evoked response of the rod outer segment tips from the retinal pigment epithelium-Bruch's membrane complex. In humans, an adaptive optics line-scan OCT facilitated high-speed recordings in rods. The non-invasive in vivo optical imaging of rhodopsin activation extends the diagnostic capability of optoretinography, and may facilitate personalized, objective assessment of rod dysfunction and visual cycle impairment in inherited and age-related macular degeneration.},
}

@article {pmid41494750,
year = {2026},
author = {Balser, S and Capsius, B and Hole, R and Papp, A and Preissinger, N and Rozenknop, A and Tiko, T},
title = {Randomised, double-masked trial to compare the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration.},
journal = {BMJ open ophthalmology},
volume = {11},
number = {1},
pages = {},
pmid = {41494750},
issn = {2397-3269},
mesh = {Humans ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage ; Double-Blind Method ; Male ; Female ; *Recombinant Fusion Proteins/administration & dosage ; Aged ; *Biosimilar Pharmaceuticals/administration & dosage/therapeutic use/adverse effects ; Intravitreal Injections ; *Visual Acuity ; Middle Aged ; Treatment Outcome ; *Wet Macular Degeneration/drug therapy/diagnosis/physiopathology ; Angiogenesis Inhibitors/administration & dosage ; Aged, 80 and over ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Tomography, Optical Coherence ; Follow-Up Studies ; },
abstract = {OBJECTIVE: Biosimilars are helping to reduce the cost burden of treatment and widen patient access to therapies. This multicentre trial compared the efficacy, safety and immunogenicity of the biosimilar aflibercept FYB203 with reference aflibercept in patients with neovascular age-related macular degeneration (nAMD).

METHODS AND ANALYSIS: Patients aged ≥50 years with newly diagnosed nAMD and a best-corrected visual acuity (BCVA) between 20/40 and 20/200 Snellen equivalent were randomised (1:1) to double-masked treatment with 2 mg FYB203 or EU-approved reference aflibercept by intravitreal injection every 4 weeks for three doses (baseline, weeks 4 and 8) then every 8 weeks up to week 48. The primary efficacy endpoint was the change from baseline in BCVA by Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 8 in the study eye. Therapeutic equivalence of FYB203 and reference aflibercept was demonstrated if, depending on the regulatory requirement with respect to the significance level, the two-sided 90.4% and 95.2% CIs were within the predefined equivalence interval of (-3.5 to 3.5) ETDRS letters.

RESULTS: A total of 433 patients received treatment with FYB203 (n=215) or reference aflibercept (n=218). Mean improvement in BCVA from baseline to week 8 was 6.6 ETDRS letters with FYB203 and 5.6 ETDRS letters with reference aflibercept, with an estimated mean treatment difference of 1.0 and the two-sided 90.4% CI (-0.3 to 2.2) and 95.2% CI (-0.6 to 2.5) fully contained within the pre-defined equivalence margins, confirming therapeutic equivalence between FYB203 and reference aflibercept. Safety and immunogenicity profiles were similar between groups.

CONCLUSION: Although conducted during the COVID-19 pandemic in a potentially vulnerable elderly population and affected by geopolitical disruption in Ukraine, mitigation measures minimised the overall impact of these events. FYB203 demonstrated therapeutic equivalence to reference aflibercept in patients with nAMD, supporting similar clinical performance across all approved indications.

TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT04522167; EudraCT: 2019-003923-39.},
}

Humans
*Receptors, Vascular Endothelial Growth Factor/administration & dosage
Double-Blind Method
Male
Female
*Recombinant Fusion Proteins/administration & dosage
Aged
*Biosimilar Pharmaceuticals/administration & dosage/therapeutic use/adverse effects
Intravitreal Injections
*Visual Acuity
Middle Aged
Treatment Outcome
*Wet Macular Degeneration/drug therapy/diagnosis/physiopathology
Angiogenesis Inhibitors/administration & dosage
Aged, 80 and over
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Tomography, Optical Coherence
Follow-Up Studies

@article {pmid41493658,
year = {2026},
author = {Tan, X and Kang, J and Zhao, H and Fang, F and Xia, Y and Luo, C and Zou, Y and Li, Y},
title = {GPR40 Attenuates Age-Related Macular Degeneration by Suppressing Retinal Microglial NLRP3 Inflammasome Activation Via ERK Signaling.},
journal = {Inflammation},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10753-025-02380-8},
pmid = {41493658},
issn = {1573-2576},
support = {82360213//the National Natural Science Foundation of China/ ; 82360213//the National Natural Science Foundation of China/ ; 82360213//the National Natural Science Foundation of China/ ; 82360213//the National Natural Science Foundation of China/ ; 202305AC160073//the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202305AC160073//the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202305AC160073//the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202305AC160073//the Yunnan Provincial Young and Middle - Aged Academic and Technical Leaders Reserve Talents Project/ ; 202401AY070001-172/174//the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; 202401AY070001-172/174//the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; 202401AY070001-172/174//the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; 202401AY070001-172/174//the Yunnan Provincial Department of Science and Technology - Kunming Medical University Joint Fund for Applied Basic Research/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; ZKF2024048/ ZKF2024047//The National Key Clinical Specialty Project in Ophthalmology/ ; 2024Y927//Yunnan Provincial Department of Education Scientific Research Fund Project/ ; 2024Y927//Yunnan Provincial Department of Education Scientific Research Fund Project/ ; 2024Y927//Yunnan Provincial Department of Education Scientific Research Fund Project/ ; 2024Y927//Yunnan Provincial Department of Education Scientific Research Fund Project/ ; },
abstract = {Retinal neuroinflammation is a key pathological feature of age-related macular degeneration (AMD), primarily driven by aberrant microglial cell activation. The expression and role of G-protein-coupled receptor 40 (GPR40), in AMD remain unclear. To investigate this pathology, we established a sodium iodate-induced mouse model of non-exudative AMD and performed in vitro experiments using LPS-stimulated microglial cells. The results showed that activation of the GPR40 receptor significantly promoted the polarization of microglial cells from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, effectively inhibiting neuroinflammation. Mechanistic studies revealed that GPR40 negatively regulates the ERK signaling pathway, inhibiting NLRP3 inflammasome activation and the release of pro-inflammatory cytokines such as IL-1β and TNF-α. In both in vivo and in vitro experiments, GPR40 activation protected photoreceptors by suppressing neuroinflammation caused by excessive microglial activation. In conclusion, this study reveals, for the first time, the critical role of GPR40 in regulating retinal neuroinflammation and its molecular mechanism. It highlights the potential therapeutic value of targeting the GPR40-ERK signaling axis to control the neuroinflammatory cascade and delay the progression of AMD and other retinal degenerative diseases.},
}

@article {pmid41493078,
year = {2026},
author = {Zobor, D and Munk, MR},
title = {Distinguishing Inherited Retinal Disease From Age-Related Macular Degeneration: Clinical Red Flags, Diagnostic Strategy, and the Expanding Role of Genetic Testing.},
journal = {Clinical & experimental ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1111/ceo.70055},
pmid = {41493078},
issn = {1442-9071},
}

@article {pmid41492569,
year = {2026},
author = {Faghihi, S and Eshkoly-Lior, T and Feo, A and Sarraf, D},
title = {Atypical presentation of macular serpiginous choroiditis masquerading as age related macular degeneration.},
journal = {American journal of ophthalmology case reports},
volume = {41},
number = {},
pages = {102491},
pmid = {41492569},
issn = {2451-9936},
abstract = {PURPOSE: To describe a case of macular serpiginous choroiditis (SC) masquerading as age related macular degeneration.

METHOD: Multimodal imaging (MMI), including ultra-widefield fundus autofluorescence and fluorescein and indocyanine green angiography werer performed. Cross-sectional and en face optical coherence tomography (OCT) and OCT angiography (OCTA) facilitated the correct diagnosis of this masquerade condition.

RESULTS: A 57-year-old woman, with a history of long-standing vision loss in the left eye (OS), presented with acute vision loss in the right eye (OD). Color fundus photography showed a focal macular lesion central OD and an irregular atrophic macular scar central OS. OCT OD displayed large drusenoid lesions in the macula OD and a macular scar OS. OCTA showed evidence of inner choroidal ischemia central OD corresponding to the drusenoid lesions without shadow artifact OD. A diagnosis of macular serpiginous choroiditis was rendered OD and the patient was started on immunomodulatory therapy (IMT) including oral steroids and increasing dosages of mycophenolate therapy. After three months of follow-up, the visual acuity remarkably improved, the drusenoid lesions completely resolved on OCT, and choroidal ischemia completely regressed on OCTA OD.

CONCLUSION: Placoid disorders can masquerade as AMD. We present an unusual case of macular serpiginous choroiditis with new onset drusenoid lesions driven by inner choroidal ischemia on OCTA and with resolution following IMT. OCTA can be an invaluable tool to correctly diagnose placoid conditions which is essential to guide therapeutic considerations.},
}

@article {pmid41491515,
year = {2026},
author = {Wang, JX and Wei, WB},
title = {[Research status of subretinal fibrosis in age-related macular degeneration].},
journal = {[Zhonghua yan ke za zhi] Chinese journal of ophthalmology},
volume = {62},
number = {1},
pages = {66-72},
doi = {10.3760/cma.j.cn112142-20250804-00330},
pmid = {41491515},
issn = {0412-4081},
support = {82220108017, 82141128//National Natural Science Foundation of China/ ; 2024-1-2052//The Capital Health Research and Development of Special/ ; Z201100005520045//Science & Technology Project of Beijing Municipal Science & Technology Commission/ ; SZSM202311018//Sanming Project of Medicine in Shenzhen/ ; },
mesh = {*Macular Degeneration/pathology ; Humans ; Animals ; Fibrosis ; *Retina/pathology ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of vision loss in individuals aged 65 years and older. In the advanced stage of the disease, subretinal fibrotic scars develop, leading to irreversible vision impairment. The formation of subretinal scars is driven by interactions among various cellular and molecular components, involving multiple pathological processes including immune responses and inflammatory reactions; however, the exact underlying mechanism remains elusive. This review summarizes the current animal models and experimental studies employed to investigate its mechanism and explore novel therapeutic targets.},
}

*Macular Degeneration/pathology
Humans
Animals
Fibrosis
*Retina/pathology
Disease Models, Animal

@article {pmid41491306,
year = {2026},
author = {Kikushima, W and Sakurada, Y and Fukuda, Y and Yoneyama, S and Kotoda, Y and Tsuru, DV and Kashiwagi, K},
title = {Brolucizumab versus aflibercept in treating exudative age-related macular degeneration: a 12-month pro re nata regimen.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-34984-x},
pmid = {41491306},
issn = {2045-2322},
}

@article {pmid41490968,
year = {2026},
author = {Mastropasqua, R and Quarta, A and Passamonti, M and Lorenzi, C and Ruggeri, ML and Gironi, M and Persavalli, C and Belloni Baroni, L and De Santis Ciacci, C and Aloia, R and Della Penna, N and Toto, L and Carpineto, P and Mastropasqua, L},
title = {Macular pigment optical density following lutein scleral iontophoresis in intermediate age-related macular degeneration: A six-month pilot study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328403},
pmid = {41490968},
issn = {1468-2079},
abstract = {PURPOSE: To evaluate the effects of scleral iontophoresis lutein delivery on macular pigment optical density (MPOD), retinal anatomy and function in patients with intermediate age-related macular degeneration (iAMD).

METHODS: This prospective pilot study included 15 phakic eyes from patients with iAMD. All participants underwent a single session of trans-scleral iontophoresis with a liposomal lutein formulation. MPOD, central macular thickness (CMT), choroidal vascularity index (CVI) and retinal sensitivity (RS) were assessed at baseline (T0), and at 1 month (T1), 3 months (T2) and 6 months (T3).

RESULTS: MPOD showed a significant overall change across time points (χ²=11.01, p=0.012), with significant differences between T1 and T3 (p=0.006) and T2 and T3 (p=0.018). CMT significantly decreased at T3 compared with earlier visits (p≤0.002). RS declined at early time points (T1 and T2 vs T0; p=0.027 and p=0.002, respectively), while CVI exhibited modest reductions by T2 and T3 (p=0.021 and p=0.017). A significant inverse correlation was found between ΔMPOD and ΔRS at T2-T0 (ρ=-0.520, p=0.035). Best-corrected visual acuity remained stable across all visits.

CONCLUSIONS: The inverse correlation between MPOD change and RS decline at 3 months raises the possibility that early augmentation of MP may provide a protective functional effect. These data support the short-term feasibility of scleral iontophoresis for targeted lutein delivery.},
}

@article {pmid41490387,
year = {2025},
author = {Franco, JJ and Wubben, TJ},
title = {Emerging solutions for neovascular age-related macular degeneration.},
journal = {Current opinion in ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICU.0000000000001199},
pmid = {41490387},
issn = {1531-7021},
abstract = {PURPOSE OF REVIEW: To summarize emerging therapeutic strategies for neovascular (wet) age-related macular degeneration (nAMD), with emphasis on recent translational and clinical developments.

RECENT FINDINGS: The nAMD treatment landscape is rapidly evolving. Gene therapies (e.g. ABBV-RGX-314, ADVM-022, and 4D-150) have demonstrated sustained intraocular anti-VEGF expression with reduced injection burden in phase 2 and 3 programs, validating the 'biofactory' concept. Tyrosine kinase inhibitors delivered via intravitreal or suprachoroidal implants (e.g. EYP-1901, OTX-TKI, and CLS-AX) show potential for twice-yearly or less frequent dosing. Moreover, emerging therapeutic approaches increasingly target non-VEGF pathogenic pathways, reflecting a shift toward mechanistically diverse vascular stabilization and neuroprotection strategies. These include multitargeted biologics that couple anti-angiogenic and anti-inflammatory effects (e.g. KSI-501, IBI-302, and AG-73305), as well as agents modulating FGF2 signaling, Wnt activation, complement regulation, and cellular metabolism.

SUMMARY: Therapeutic innovation in nAMD is transitioning from incremental refinements in intravitreal anti-VEGF delivery to strategies aimed at extending durability or targeting alternative contributory pathways. Long-term safety, efficacy, and durability will determine which of these candidates redefine standard care.},
}

@article {pmid41490202,
year = {2025},
author = {Peschaut, T and Seidel, G and Sommer, M and Kruger, M and Nadvornik, C and Werkl, PJ},
title = {Recurrent sterile endophthalmitis following intravitreal Faricimab: A case report.},
journal = {Retinal cases & brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001854},
pmid = {41490202},
issn = {1937-1578},
abstract = {PURPOSE: Despite its low risk profile and high efficacy described in several studies, there appears to be an increasing number of reports describing sterile inflammatory reactions following intravitreal administration of Faricimab. Purpose of this case report is to highlight the occurrence of recurrent sterile endophthalmitis following repeated intravitreal Faricimab administration, emphasizing the need for awareness and careful monitoring of this adverse reaction.

METHODS AND RESULTS: We present the case of an 83-year-old caucasian woman, who was treated with intravitreal Faricimab for neovascular age-related macular degeneration (nAMD) in her left eye (OS). Shortly after the first administration, she experienced progressive, painless visual deterioration, along with a pronounced inflammatory reaction in the anterior and posterior segments, including granulomatous keratic precipitates. Based on these findings, the diagnosis of endophthalmitis was made. Following hospital admission, immediate treatment led to resolution of the condition and recovery of visual acuity.On the first day after the second administration of Faricimab, the patient again experienced painless visual deterioration accompanied by a severe inflammatory reaction OS. Immediate treatment once more resulted in resolution of the condition and recovery of visual acuity. In both instances, no microbial growth was detected in fungal cultures or aerobic and anaerobic cultures from aqueous humor and vitreous samples.

CONCLUSION: We present a case of recurrent endophthalmitis in the same patient following two intravitreal administrations of Faricimab. Considering the clinical presentation and course, as well as the microbiological findings, a sterile inflammatory reaction is likely in both instances.},
}

@article {pmid41490049,
year = {2025},
author = {Dor, O and Cohen, M and Shahar-Gonen, M and Loewenstein, A and Peto, T and Wright, D and Shor, R and Havilio, M and Benyamini, G and Wen, Q and Shomron, N and Zur, D},
title = {Anti-VEGF Therapy Switching in Neovascular Age-Related Macular Degeneration: Insights from Automated Volumetric Retinal Fluid Analysis.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004756},
pmid = {41490049},
issn = {1539-2864},
abstract = {PURPOSE: To evaluate the efficacy of switching from bevacizumab to ranibizumab or aflibercept in neovascular age-related macular degeneration (nAMD) using automated volumetric retinal fluid analysis.

METHODS: This retrospective study included 186 eyes with nAMD showing inadequate response after ≥3 bevacizumab injections. Patients were switched to a second-line anti-VEGF agent and categorized as early (3-5 injections) or late (≥6 injections) switchers. Optical coherence tomography (OCT) scans were analyzed using the Notal-OCT Analyzer (NOA™), an AI-based algorithm for retinal fluid quantification. Parameters included total retinal fluid (TRF), intraretinal fluid (IRF) volume, subretinal fluid (SRF) volume, pigment epithelial detachment (PED) volume, central subfield thickness (CST), and visual acuity (VA), assessed at baseline, post-bevacizumab, and following three injections of the new agent.

RESULTS: Early switchers showed an increase in TRF from 105nL to 158nL after bevacizumab, then a reduction to 20nL post-switch (p<0.001); PED volume decreased post-switch (p=0.010). Late switchers showed fluid reductions both after bevacizumab and post-switch (TRF: p<0.001; PED: p=0.007). CST significantly improved only in early switchers (p=0.004), while VA changes were not statistically significant.

CONCLUSIONS: Automated fluid analysis reliably quantifies treatment response in nAMD. Early switchers showed worsening after bevacizumab, while late switchers had partial responses. These findings highlight the potential of automated analysis to support more individualized, data-driven treatment strategies. Prospective studies are required to confirm impact on patient outcomes.},
}

@article {pmid41488355,
year = {2025},
author = {Zhang, Q and Zhang, H and Shi, X and Li, J and Wang, C and Zhou, H and Shan, C},
title = {Noninvasive transcranial brain stimulation for eye diseases and visual dysfunctions: A systematic review of RCTs.},
journal = {iScience},
volume = {28},
number = {12},
pages = {114111},
pmid = {41488355},
issn = {2589-0042},
abstract = {Noninvasive transcranial brain stimulation (NTBS) has emerged as a potential therapeutic approach for eye diseases and visual dysfunctions. This systematic review evaluates the evidence from 23 randomized controlled trials examining the application of NTBS, including transcranial electrical stimulation and transcranial magnetic stimulation, in conditions such as amblyopia, myopia, visual field defects, glaucoma, diabetic retinopathy, macular degeneration, and blepharospasm. Studies assessed outcomes such as visual acuity, contrast sensitivity, and visual perception, with variable effects observed across trials. Most studies reported no serious adverse events, indicating that NTBS is safe and feasible. However, conclusive evidence regarding its efficacy remains elusive due to varied interventions, inconsistent outcome measures, and methodological limitations. Future research with higher methodological rigor is needed to optimize stimulation parameters and explore integration with adjunctive therapies.},
}

@article {pmid41486361,
year = {2026},
author = {Kim, JH and Park, SM and Choi, SI and Kim, DI and Sohn, J and Lee, WK},
title = {Short-term outcomes and choroidal morphological changes following aflibercept therapy in pachychoroid neovasculopathy.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31287-5},
pmid = {41486361},
issn = {2045-2322},
abstract = {To evaluate the short-term outcomes and choroidal morphological changes after three monthly aflibercept injections for pachychoroid neovasculopathy (PNV). Twenty-nine treatment-naïve patients with PNV were enrolled in this prospective phase IV clinical trial. All patients received three monthly injections of aflibercept. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured at baseline and at week 12 (4 weeks after the third injection). Additionally, changes in the subfoveal choroidal thickness (SCT), largest choroidal vessel diameter, and area of the choriocapillaris-Sattler's and Haller's layers between baseline and week 12 were assessed. The BCVA improved from 67.5 ± 10.8 Early Treatment Diabetic Retinopathy Study (ETDRS) letters at baseline to 74.3 ± 10.7 letters at week 12. CRT decreased from 348.5 ± 77.4 μm at baseline to 254.3 ± 72.9 μm at week 12. Complete resolution of the retinal fluid was observed in 86.2% of cases at week 12. At baseline and 12 weeks, the SCT measured 388.3 ± 77.4 μm and 344.9 ± 91.9 μm, respectively, while the diameter of the largest choroidal vessel measured 280.3 ± 62.0 μm and 247.8 ± 57.6 μm, respectively. The areas of the choriocapillaris-Sattler's layer and Haller's layer at the corresponding time points were 0.56 ± 0.14 mm[2] and 0.57 ± 0.14 mm[2], and 1.56 ± 0.42 mm[2] and 1.40 ± 0.45 mm[2], respectively. Aflibercept loading injections for PNV resulted in both short-term visual and anatomical improvements. Notably, the reduction in the area of Haller's layer and choroidal vessel diameter after treatment suggests that aflibercept exerts an impact on this region of the choroid.},
}

@article {pmid41484254,
year = {2026},
author = {Askarinejad, A and Lip, GYH and Lip, PL},
title = {An association between atrial fibrillation and age-related macular degeneration: looking beyond mere coincidence.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41484254},
issn = {1476-5454},
}

@article {pmid41484209,
year = {2026},
author = {Donato, L and Zerti, D and Babiloni-Chust, I and Passacantando, M and Flati, V and Feligioni, M and Carl, M and Rinaldi, C and Poggi, L and D'Angelo, R and Maccarone, R},
title = {Comprehensive transcriptomic analysis reveals canonical and novel pathways modulated by nanoceria in mammalian retinal degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-33260-8},
pmid = {41484209},
issn = {2045-2322},
support = {2022PWMW5A//Ministry of University and Research (MUR, Italy) through the PRIN (Progetti di Rilevante Interesse Nazionale) 2022 grant/ ; },
abstract = {Retinal neurodegenerative diseases such as Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa cause irreversible vision loss due to the limited regenerative capacity of the mammalian retina. Cerium oxide nanoparticles (nanoceria) are emerging therapeutics against oxidative stress and inflammation, major drivers of photoreceptor degeneration, and have demonstrated morphological and functional neuroprotection in preclinical models. However, the genome-wide transcriptional mechanisms underlying these effects remain incompletely characterized. We performed retinal transcriptomic analysis in a rat AMD model induced by intense light and treated intravitreally with nanoceria. Six groups were analyzed: control, light damage, vehicle, nanoceria, vehicle + light damage, and nanoceria + light damage. Light damage activated inflammatory and apoptotic programs, with upregulation of cytokines (Tnf, Il6, Il1b, Ccl2) and downregulation of photoreceptor genes (Rho, Pde6a/b, Gnat1). Nanoceria treatment counteracted these effects, suppressing pro-inflammatory mediators, restoring antioxidative genes (Nfe2l2, Gclc, Sod2), and enhancing neuroprotective factors (Bdnf, Cntf, Ngf). Pathway analyses revealed inhibition of TNF/NF-κB/IL-17 signaling and activation of PI3K-Akt, JAK-STAT, and neurotrophin pathways. Unexpectedly, nanoceria also modulated amino acid and insulin metabolism (Ass1, Cps1, Insr, Irs1, Slc2a4) and reactivated transcription factors (Ascl1, Sox2, Notch1) typically silent in adult retina. Our findings highlight nanoceria as a multifunctional therapeutic that mitigates retinal degeneration by coordinating oxidative, inflammatory, and regenerative responses. Together with prior morphological and functional validations, these results support the translational potential of nanoceria for treating retinal neurodegenerative diseases.},
}

@article {pmid41483391,
year = {2026},
author = {Peng, Y and Zhang, Y and Kam, KW and Ho, M and Sezto, S and Au, S and Yim, CC and Zhang, X and Ng, MPH and Ip, P and Young, A and Pang, CP and Tham, CC and Chen, LJ and Yam, JC},
title = {Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {41483391},
issn = {2509-2723},
support = {14102422//General Research Fund/ ; C7149-20G//Collaborative Research Fund/ ; 11220206//Health and Medical Research Fund/ ; 10210246//Health and Medical Research Fund/ ; 09202466//Health and Medical Research Fund/ ; 82425017//National Natural Science Foundation of China/ ; 82171089//National Natural Science Foundation of China/ ; WW/SC/rc/SIEF2324/0366/24vw//Strategic Impact Enhancement Fund/ ; TL/JF/rc/SIEF2223/0759/23vw//Strategic Impact Enhancement Fund/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at enrollment. Among them, 53,059 with at least one follow-up FP assessment comprised the trajectory cohort. Participants were categorized as nonfrail, prefrail, or frail based on their FP scores. Annualized frailty progression (ΔFP/year) was estimated via linear regression. Cox models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD. During a median follow-up of 11.8 years in the baseline cohort, 13,428 incident AMD cases (2.9%) were documented. Prefrail (HR:1.14; 95% CI:1.10-1.18) and frail (HR:1.36; 95% CI: 1.26-1.47) individuals had significantly higher AMD risks compared to nonfrail participants. In the frailty trajectory analysis with a median follow-up duration of 3.3 years, 852 incident AMD cases (1.6%) were recorded. Each 1-point FP increase conferred 28% higher AMD risk (HR: 1.28; 95% CI: 1.18-1.38), while each 0.1-point/year ΔFP increase independently elevated risk by 15% (HR: 1.15; 95% CI: 1.10-1.21). Compared to stable nonfrail, prefrailty aggravation showed highest AMD risk (HR: 2.26; 95% CI: 1.51-3.37), followed by frailty alleviation (HR: 1.73; 95% CI: 0.98-3.04) and frailty maintenance (HR: 1.72; 95% CI: 0.86-3.41). Progressive frailty trajectories, independent of baseline status, is associated with increased incident AMD risk. Early interventions targeting frailty progression may mitigate AMD risk in aging populations.},
}

@article {pmid41482231,
year = {2025},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Can Omega-3 Fatty Acids Serve as a Preventive Strategy for Age-Related Macular Degeneration? A Systematic Review and Meta-Analysis.},
journal = {The Journal of nutrition},
volume = {},
number = {},
pages = {101289},
doi = {10.1016/j.tjnut.2025.101289},
pmid = {41482231},
issn = {1541-6100},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss in older adults. While anti-VEGF therapies exist for neovascular AMD, preventive strategies remain limited. Long-chain omega-3 fatty acids (EPA/DHA) demonstrate biological plausibility for AMD protection through their roles in retinal structure (DHA) and anti-inflammatory pathways (EPA-derived mediators).

OBJECTIVE: To synthesize contemporary evidence on omega-3 fatty acids in age-related macular degeneration (AMD) prevention, addressing critical gaps in subtype-specific efficacy, source differentials (dietary vs. supplemental), and long-term effects.

METHODS: This systematic review and meta-analysis included 18 observational studies identified via different databases. Outcomes were pooled using random-effects models (RevMan 5.4). Subgroup analyses stratified AMD subtypes (neovascular/geographic atrophy) and omega-3 types (EPA/DHA/ALA). The Newcastle-Ottawa scale was adopted to assess the methodological quality of the included studies.

RESULTS: High omega-3 intake reduced overall AMD odds by 18% (OR: 0.82; 95% CI: 0.70-0.96, p = .01), with pronounced protection for neovascular AMD (OR: 0.57; 95% CI: 0.40-0.81) and geographic atrophy (OR: 0.65; 95% CI: 0.45-0.94). EPA/DHA significantly lowered risk (EPA OR: 0.61; DHA OR: 0.73), while ALA showed no benefit (OR: 1.00; 95% CI: 0.84-1.20). No long-term risk reduction emerged (HR: 0.98; 95% CI: 0.84-1.15, p = .83). Significant heterogeneity (I[2] = 61%) and publication bias (Egger's p = .04) were observed.

CONCLUSION: Dietary EPA/DHA-particularly from fish-confers protection against AMD, especially neovascular subtypes, but supplements show no long-term benefit. Clinical recommendations should prioritize whole-food sources over isolated omega-3 formulations.},
}

@article {pmid41482136,
year = {2025},
author = {Bala, S and Allan, KC and Decker, NL and Abbass, NJ and Joo, JH and Zhao, A and Talcott, KE and Rachitskaya, AV},
title = {Glucagon-like peptide-1 receptor agonists: What ophthalmologists need to know.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.12.007},
pmid = {41482136},
issn = {1879-3304},
abstract = {Initially designed for the treatment of type-2 diabetes, glucagon-like peptide-1 receptor agonists (GLP-1RA) are multifaceted agents with promising neuroprotective and anti-inflammatory properties. The majority of the research exploring the relationship between GLP-1RA use and ophthalmic disease comes from large database studies or secondary-analysis of randomized controlled trials investigating GLP-1RAs in cardiovascular disease and obesity. Current evidence regarding the impact of GLP-1 receptor agonists on ophthalmic diseases remains inconsistent, with studies reporting both protective and detrimental effects. For example, there are conflicting findings of an effect on diabetic retinopathy and non-arteritic anterior ischemic optic neuropathy, as well as age-related macular degeneration, with GLP-1RA use. In contrast, GLP-1RAs have more consistently demonstrated a protective effect against idiopathic intracranial hypertension, glaucoma and dry-eye disease. Importantly, the majority of the clinical ophthalmic studies are from large electronic health record databases. Overall, limitations in the design of these studies, such as the lack of manual chart review and potential miscoding of diagnosis or treatments, prohibit a more granular analysis of comprehensive ocular endpoints. As a heterogenous medication class with differing structures, potencies, and mechanisms of action, we outline the ophthalmic effects of all Food and Drug Administration-approved GLP-1RAs. We discuss the proposed mechanisms of ocular effects and GLP-1RA use, examine the current literature investigating the impact of GLP-1RAs on ophthalmic disease, discuss the effects of specific GLP-1RAs, and outline the perioperative considerations of this medication class.},
}

@article {pmid41481850,
year = {2025},
author = {Yuan, M and Alsoudi, A and Alshaikhsalama, A and Rahimy, E},
title = {Systemic medications and their impact on age-related macular degeneration development and progression: a review of current evidence.},
journal = {Current opinion in ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICU.0000000000001198},
pmid = {41481850},
issn = {1531-7021},
abstract = {PURPOSE OF REVIEW: This review examines commonly prescribed systemic medications and their possible associations with age-related macular degeneration (AMD) development and progression. With the limitations and risks of current intravitreal therapies, there is growing interest in oral pharmacotherapy for AMD management. The following review synthesizes observational studies, meta-analyses, and ongoing clinical trials to evaluate the potential effects of commonly used systemic medications on AMD.

RECENT FINDINGS: Metformin demonstrates conflicting evidence, with several meta-analyses and large cohort study showing reduced AMD odds, while a recent randomized phase II trial found no effect on geographic atrophy progression. For statins, emerging evidence suggests that treatment duration exceeding 2 years and medium-intensity to high-intensity dosing may confer protection against AMD development. Aspirin demonstrates discordant results between different study designs: two large randomized controlled trials showed no benefit for AMD, while a 10-year observational study suggested protective effects.Fenofibrates show promise in preclinical models but require additional clinical investigation. Danicopan also shows modest effects in complement-related disorders and is currently undergoing a phase 2 trial to evaluate efficacy in patients with geographic atrophy. Finally, dopamine agonists appear to improve visual acuity and reduce subretinal fluid and central retinal thickness in newly diagnosed exudative AMD, as shown in an open-label pilot study, but require further investigation.

SUMMARY: Multiple systemic medications have highlighted mixed or stage-dependent benefits on AMD development and progression. Some agents such as metformin and aspirin have shown conflicting findings, having been evaluated in randomized trials and large observational studies. Other medications including GLP-1 agonists, dopamine agonists, statins, fenofibrates, and danicopan show early promise in more limited studies, but require further clinical validation.},
}

@article {pmid41480686,
year = {2026},
author = {Oltra, M and Martínez-Santos, M and Ybarra, M and Pires, M and Ceresoni, C and Gomis-Coloma, C and Medina-Trillo, C and Sancho, J and Barcia, J},
title = {miR‑205: A dual regulator of angiogenesis in health and disease (Review).},
journal = {International journal of molecular medicine},
volume = {57},
number = {2},
pages = {},
doi = {10.3892/ijmm.2025.5722},
pmid = {41480686},
issn = {1791-244X},
mesh = {*MicroRNAs/genetics/metabolism ; Humans ; *Neovascularization, Pathologic/genetics/metabolism ; Animals ; Extracellular Vesicles/metabolism/genetics ; *Neovascularization, Physiologic/genetics ; Cell Proliferation ; Angiogenesis ; },
abstract = {The present study evaluated the role of microRNA (miR)‑205 as a dual regulator of angiogenesis, exhibiting both pro‑angiogenic and anti‑angiogenic effects depending on the biological context. miRs are small non‑coding sequences that regulate gene expression at the post‑transcriptional level and can be transported in extracellular vesicles (EVs), allowing them to modulate biological processes remotely. miR‑205 is involved in multiple cellular processes, such as proliferation, migration, apoptosis and angiogenesis. In angiogenesis its function is contradictory: On one hand, it can inhibit blood vessel formation by suppressing pro‑angiogenic factors such as VEGF and ANG‑2, as demonstrated in diseases such as psoriasis, thyroid cancer and diabetic retinopathy. However, in other contexts, miR‑205 promotes angiogenesis by inhibiting anti‑angiogenic genes such as PTEN and HITT, facilitating the activation of the PI3K/AKT pathway and cell proliferation in ovarian cancer and thrombosis. Additionally, the present study highlighted the role of EVs in transferring miR‑205 between cells, thereby influencing angiogenesis and disease progression. Studies in myocardial infarction and cancer models have demonstrated that EVs enriched in miR‑205 can affect blood vessel formation and tumor progression. Similarly, in ocular diseases such as macular degeneration and diabetic retinopathy, miR‑205 encapsulated in EVs has shown therapeutic potential by regulating VEGF levels. In conclusion, miR‑205 emerges as a promising therapeutic target for angiogenic diseases. Its application in EV‑based therapy could represent an innovative strategy for treating vascular disorders. However, further studies are needed to fully understand its mechanisms of action and optimize its clinical application.},
}

*MicroRNAs/genetics/metabolism
Humans
*Neovascularization, Pathologic/genetics/metabolism
Animals
Extracellular Vesicles/metabolism/genetics
*Neovascularization, Physiologic/genetics
Cell Proliferation
Angiogenesis

@article {pmid41480395,
year = {2025},
author = {Zeppieri, M and Visalli, F and Musa, M and Avitabile, A and Giglio, R and Tognetto, D and Gagliano, C and D'Esposito, F and Cappellani, F},
title = {Novel developments in retinal regeneration: Advances and future outlooks in stem cell therapy.},
journal = {World journal of stem cells},
volume = {17},
number = {12},
pages = {111374},
pmid = {41480395},
issn = {1948-0210},
abstract = {Retinal degenerative diseases, such as age-related macular degeneration, retinitis pigmentosa, and Stargardt disease, are primary contributors to irreversible vision loss globally. Due to the scarcity of effective curative treatments, stem cell therapy has emerged as a revolutionary advancement in ophthalmology. In the last ten years, significant advancements have been achieved in the derivation of retinal pigment epithelium and photoreceptor precursors from human embryonic stem cells and induced pluripotent stem cells, with initial clinical trials indicating safety and potential efficacy. Innovative delivery platforms, such as biodegradable scaffolds, microcarrier suspensions, and minimally invasive subretinal devices, are tackling prior challenges related to cell survival and integration. Simultaneously, gene-edited and patient-specific induced pluripotent stem cells are positioned to surmount immunological and ethical constraints. Future combinatorial strategies that incorporate stem cells with gene therapy, CRISPR-mediated editing, and bioengineered retinal organoids offer potential for personalized and regenerative methodologies. Nonetheless, enduring functional integration, immune tolerance, and oncogenic safety continue to pose significant challenges. To effectively transition from laboratory research to clinical application, collaborative frameworks among academic institutions, biotechnology companies, and regulatory agencies will be crucial for unlocking the complete therapeutic potential of stem cell-based treatments for retinal diseases. Stem cell therapy has transitioned from a distant promise to an advancing reality set to transform retinal care.},
}

@article {pmid41479867,
year = {2025},
author = {Priyanka, P and Khullar, S and Singh, M and Morya, AK and Sharma, B and Periasamy, B and Moharana, B and Morya, R},
title = {Role of gut microbiomes in different ocular pathologies: A systematic review.},
journal = {World journal of gastrointestinal pathophysiology},
volume = {16},
number = {4},
pages = {113488},
pmid = {41479867},
issn = {2150-5330},
abstract = {BACKGROUND: The gut microbiome is integral to human health, with emerging research underscoring its potential impact on ocular health through the gut-eye axis. Various ocular disorders, such as dry eye syndrome, retinal vascular diseases, macular degeneration, and glaucoma, may be influenced by gut dysbiosis, which could significantly contribute to their development and progression.

AIM: To evaluate the influence of the gut microbiome on the pathogenesis and progression of various ocular diseases.

METHODS: An extensive search of the scientific literature was undertaken by adhering to Preferred Reporting Items for Systematic Reviews & Meta-Analyses standards, using PubMed (MEDLINE), Scopus, EMBASE, and the Cochrane Library as sources to locate studies addressing the relationship between the gut microbiome and human health. To capture all relevant publications, search terms were systematically applied across these major databases, without limiting the search by language or publication date. Inclusion criteria covered randomized controlled trials, non-randomized controlled trial, prospective studies, cross-sectional studies, and case-control studies. Out of the 3077 articles, 36 full texts were included in the review.

RESULTS: Ocular health appears to be shaped by the gut microbial community through mechanisms such as immune regulation, preservation of the blood-retinal barrier, and the generation of protective metabolites. Disturbances in this microbial balance can provoke measurable alterations in host immunity, providing a plausible immunopathogenic pathway that connects intestinal dysbiosis with eye disease. Both laboratory models and early human data suggest that targeted interventions, including prebiotics, probiotics, synbiotics, and faecal microbiota transfer, hold therapeutic potential.

CONCLUSION: The gut-eye relationship reflects a multifaceted interaction in which the intestinal microbiome contributes to ocular health through complex biological pathways. Integrating microbiome assessments into diagnostic methods can revolutionize disease management through early detection and targeted interventions. Further, randomised controlled clinical trials are necessary for ocular diseases to prove causal relationships.},
}

@article {pmid41479851,
year = {2025},
author = {Zhang, E and Bylund, R and Zhang, A and Massop, D},
title = {Alpha-Gal Syndrome Allergy to Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251400700},
pmid = {41479851},
issn = {2474-1272},
abstract = {Purpose: To describe a case of allergic reaction to intravitreal (IVT) injection of antivascular endothelial growth factor (anti-VEGF) medications in patients with alpha-gal syndrome. Methods: A single case was evaluated. Results: A 57-year-old woman with a known diagnosis of alpha-gal syndrome was evaluated. Clinical presentation, prior treatment history, and response to different anti-VEGF agents were reviewed. The patient presented with worsening vision in her right eye due to a subfoveal choroidal neovascular membrane secondary to neovascular age-related macular degeneration in the right eye. She had experienced a systemic allergic reaction following an IVT injection of bevacizumab, but subsequently tolerated ranibizumab without any adverse effects, resulting in improvement in her vision. Conclusions: Bevacizumab, aflibercept, and faricimab are recombinant immunoglobulins produced by DNA technology in Chinese hamster ovary cells, which may contain galactose-α-1,3-galactose (alpha-gal), a potential allergen for patients with alpha-gal syndrome. Patients with alpha-gal syndrome may develop allergic reactions to certain IVT anti-VEGF agents derived from mammalian expression systems. Ranibizumab, produced using an Escherichia coli expression and lacking alpha-gal, seems to be a safe and effective option for patients with alpha-gal syndrome requiring IVT anti-VEGF therapy.},
}

@article {pmid41476611,
year = {2025},
author = {Raghavan, D and Jeakle, O and Berry, Y and Victor, M and Thummel, R},
title = {Microglia response and function in a chronic model of photoreceptor damage.},
journal = {Frontiers in cell and developmental biology},
volume = {13},
number = {},
pages = {1699271},
pmid = {41476611},
issn = {2296-634X},
abstract = {BACKGROUND: Retinal neurodegenerative diseases, including diabetic retinopathy and age-related macular degeneration, are characterized by the slow, chronic degeneration of photoreceptors. We previously used a chronic low light (CLL) exposure to model slow photoreceptor degeneration in adult zebrafish. Here, we investigate transcriptional, morphological, and functional responses of microglia in the CLL model.

METHODS: Microglia-specific gene expression analysis was mined from our previously reported 3' RNA-seq data performed at 8 time points during 28 days of CLL exposure. Morphological changes were performed on retinas collected at various time points using immunohistochemistry. Microglial inhibition was accomplished pharmacologically with dexamethasone and genetically using the irf8-/- mutant fish. Finally, we returned the CLL-treated fish to normal light/dark conditions to test whether photoreceptors could recover in the context of chronic stress.

RESULTS: CLL induced dynamic, time-dependent upregulation of microglia-specific genes consistent with pro-inflammatory and pro-resolving function. Dexamethasone treatment reduced microglial numbers and exacerbated rod and cone outer segment damage, whereas irf8-/- mutants exhibited partial protection against photoreceptor damage. Notably, despite prolonged stress and damage during the CLL exposure, photoreceptor outer segments returned to near-baseline morphology after 28 days of normal light/dark recovery conditions.

DISCUSSION: Overall, these findings suggest that microglial function in chronic retinal injury is context-dependent as pharmacological and genetic methods of inhibition produced contrasting outcomes depending upon microglial polarization.},
}

@article {pmid41475545,
year = {2025},
author = {Sun, D and Tseng, VL and Yu, F and Coleman, AL},
title = {Cardiovascular Risk and Eye Health: A Prospective Cohort Study of the Pooled Cohort Equations and Ocular Disease Incidence.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2025.12.021},
pmid = {41475545},
issn = {1549-4713},
abstract = {OBJECTIVE: We assessed whether the Pooled Cohort Equations (PCE) cardiovascular risk score, used in primary care, is associated with the future age-related macular degeneration (AMD), glaucoma, diabetic retinopathy (DR), retinal vein occlusion (RVO), and hypertensive retinopathy (HTR).

DESIGN: Historical prospective cohort study.

PARTICIPANTS: We utilized electronic health record data from the All of Us (AoU) Research Program. Participants aged 40 to 79 years had to have complete variables for PCE calculation within a 6-month period between 2009 and 2015. We excluded participants with pre-existing atherosclerotic cardiovascular disease or any of the five ocular diseases before the baseline PCE period. A total of 35,909 adults included in this study.

METHODS: Individual level PCE score was computed and categorized into four PCE risk categories: Low (<5%), Borderline (5-7.4%), Intermediate (7.5-19.9%), and High (≥20%). Time-to-event analyses included Kaplan-Meier curves, univariate and multivariable Cox proportional hazards regression models. The primary multivariable models adjusted for race, body mass index, chronic kidney disease, and education (not included in PCE to avoid over-adjustment). Concordance index (C-index) was reported to assess model performance. Sensitivity analyses tested varied follow-up durations (5,6,7 years) and, in a prespecified component-adjustment sensitivity set, sequentially added PCE components (age, smoking, diabetes).

MAIN OUTCOME MEASURES: Diagnoses of AMD, glaucoma, DR, RVO, or HTR.

RESULTS: Higher PCE risk categories were significantly associated with increased risk of ocular diseases. In the primary models, compared to the Low-risk group, the High-risk group had the highest hazard ratios for AMD (6.22), DR (5.93), glaucoma (2.33), RVO (3.38), and HTR (4.47) (all p < 0.001). Adjusted C-indices were highest for AMD (0.72), DR (0.751), and HTR (0.768), and moderate for glaucoma (0.625) and RVO (0.654). Findings were consistent in different follow-up periods. In component-adjustment sensitivity models, PCE-AMD association was largely explained by age, whereas associations for DR and HTR remained robust.

CONCLUSIONS: In the AoU population, the single composite metric PCE meaningfully stratifies future risk for multiple ocular diseases, using information already available in primary care. This suggests PCE could be incorporated into primary care settings to identify individuals who would benefit from earlier ophthalmologic evaluation and prevention strategies.},
}

@article {pmid41472698,
year = {2025},
author = {Keim, D and Dehne, M and Miller, P and Jérôme, V and Bahnemann, J and Freitag, R},
title = {High-Efficiency l‑PEI-Based Transfection of ARPE-19 Cells Using a Multiparametric Approach and Automated Polyplex Formation with a 3D-Printed Microfluidic System.},
journal = {Chem & bio engineering},
volume = {2},
number = {12},
pages = {695-710},
pmid = {41472698},
issn = {2836-967X},
abstract = {Nonviral gene delivery offers promise for treating age-related macular degeneration (AMD), a major cause of blindness. Genetic modification of retinal pigment epithelium (RPE) cells is a potential therapeutic strategy for AMD. This study presents a multiparametric approach to enhance nonviral transfection of human ARPE-19 cells using linear poly-(ethylenimine) (l-PEI, 25 kDa) as a delivery agent for plasmid DNA (pDNA). The transfection protocol was optimized by adjusting the N/P ratio through nucleic acid concentration, varying polymer density, reducing transfection volume, and minimizing contact time between cells and polyplexes. Under optimized conditions, transfection efficiency (TE) reached 88% with ∼85% viability. A semi-automated method for polyplex formation was developed using a 3D-printed microfluidic system, thereby enabling standardized production. This optimized protocol was successfully adapted to the microfluidic system without compromising TE or viability. This semi-automated approach represents a step toward the scalable and reproducible application of l-PEI-based transfection technologies for future therapeutic use.},
}

@article {pmid41471372,
year = {2025},
author = {Park, S and Won, J and Heo, JB and Kang, J and Oh, YW and Park, G and Lee, G and Lee, JH and Song, GY and Kang, W and Oh, S},
title = {The Therapeutic Effect of a Biodegradable Long-Acting Intravitreal Implant Containing CGK012 on Neovascular Age-Related Macular Degeneration by Promoting β-Catenin Degradation.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {12},
pages = {},
pmid = {41471372},
issn = {1424-8247},
support = {RS-2023-00259081//Ministry of Science and ICT, Ministry of Trade, IndKorea Drug Development Fund funded by Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfareustry, and Energy, and Ministry of Health and Welfare/ ; },
abstract = {Background/Objectives: Neovascular age-related macular degeneration (nAMD) poses a serious threat to the eyesight of older adults, representing a leading cause of irreversible vision loss. Anti-vascular endothelial growth factor (anti-VEGF) treatments are effective but require repeated intraocular injections and show poor responses in some patients. CGK012 is a novel derivative of decursin that inhibits the Wnt/β-catenin pathway. This study aimed to elucidate the mode of action of CGK012 and examine its therapeutic effects. Methods: We performed in vitro cellular studies in a retinal pigment epithelial (RPE) cell line (ARPE-19) and human umbilical vein endothelial cells (HUVECs). We examined the in vivo efficacy of CGK012-loaded implants in laser-induced choroidal neovascularization (CNV) rabbit models. We also determined the implants' in vitro dissolution, intraocular release, and disposition characteristics. Results: CGK012 decreased angiogenic/proinflammatory factor expression and suppressed the epithelial-mesenchymal transition (EMT) in RPE cells by promoting intracellular β-catenin degradation. Additionally, it repressed the expression of cyclin D1 and c-myc, downstream target genes of β-catenin, and inhibited HUVEC capillary tube formation. CGK012-loaded poly (lactic-co-glycolic acid) (PLGA) intravitreal implants significantly reduced vascular leakage in a laser-induced CNV rabbit model. Notably, CGK012 released from the implant was highly permeable to retina/choroid tissue and downregulated β-catenin, angiogenic/inflammatory factors, and vimentin in the rabbit model. The CGK012 concentration reached a plateau at 28-42 days in the vitreous humor and decayed with a half-life of 14 days without systemic exposure. Conclusions: Our findings demonstrate that CGK012 implants prevent choroidal neovascularization through the Wnt/β-catenin pathway suppression and produce high concentrations of CGK012 in the posterior eye segment with prolonged release. Thus, these implants provide more therapeutic choices for nAMD treatment.},
}

@article {pmid41470237,
year = {2025},
author = {Anitua, E and Muruzabal, F and Recalde, S and de la Fuente, M and Reparaz, I and Azkargorta, M and Elortza, F and Alkhraisat, MH},
title = {Proteomic Insights into the Retinal Response to PRGF in a Mouse Model of Age-Related Macular Degeneration.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {12},
pages = {},
pmid = {41470237},
issn = {1648-9144},
support = {ZL-2021/00557//Basque Government/ ; },
mesh = {Animals ; Mice ; Disease Models, Animal ; *Proteomics/methods ; Mice, Inbred C57BL ; *Macular Degeneration/physiopathology/drug therapy ; *Retina/drug effects/physiopathology ; *Intercellular Signaling Peptides and Proteins/therapeutic use/pharmacology ; Signal Transduction/drug effects ; Iodates ; Oxidative Stress/drug effects ; Geographic Atrophy ; },
abstract = {Background and Objectives: The aim of this study is to employ quantitative proteomics to elucidate the molecular mechanism and signaling pathways modulated by plasma rich in growth factors (PRGF) in a murine model of geographic atrophy (GA)-like retinal degeneration. Materials and Methods: C57BL/6J mice were used as a model GA-like retinal degeneration by a single systemic NaIO3 administration. Animals were divided into three groups: Control (PBS), Disease (NaIO3 + PBS), and PRGF-treated (NaIO3 + PRGF). After 7 days, retinas and retinal pigment epithelium were collected for proteomic analysis. Proteins were extracted, digested using the FASP method, and analyzed by Data-Independent Acquisition (DIA-PASEF) mass spectrometry; data were processed with DIA-NN and statistically analyzed with Perseus. Functional pathway analysis was performed using Ingenuity Pathway Analysis. Results: A total of 6511 proteins were identified. The Disease model showed the expected deregulation of pathways related to oxidative stress, inflammation, and fibrosis. Comparison between the PRGF and Control groups showed that PRGF significantly reduced oxidative and cellular stress proteins/pathways. In the same way, when PRGF and Disease groups were compared, PRGF treatment showed a significant reduction in pathways associated with inflammation, oxidative stress, and cellular stress. PRGF also activated several homeostatic pathways not only related to neuroprotective pathways but also with the lipid deposition (drusen) reduction. All these results suggest that PRGF treatment exerts a protective effect against NaIO3-induced retinal damage. Conclusions: These findings suggest that PRGF effectively mitigates the degenerative effects of NaIO3 by activating specific protective and compensatory signaling pathways in the retina. PRGF is indicated as a promising new therapeutic option for ameliorating age-related macular degeneration progression.},
}

Animals
Mice
Disease Models, Animal
*Proteomics/methods
Mice, Inbred C57BL
*Macular Degeneration/physiopathology/drug therapy
*Retina/drug effects/physiopathology
*Intercellular Signaling Peptides and Proteins/therapeutic use/pharmacology
Signal Transduction/drug effects
Iodates
Oxidative Stress/drug effects
Geographic Atrophy

@article {pmid41470194,
year = {2025},
author = {Busquets, MA and Garfinkel, RA and Sambhara, D and Mohan, N and Nahen, K and Benyamini, G and Loewenstein, A},
title = {Home Monitoring for the Management of Age-Related Macular Degeneration: A Review of the Development and Implementation of Digital Health Solutions over a 25-Year Scientific Journey.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {12},
pages = {},
pmid = {41470194},
issn = {1648-9144},
mesh = {Humans ; *Macular Degeneration/therapy/diagnosis ; Telemedicine/trends ; Monitoring, Physiologic/methods ; Digital Health ; },
abstract = {The management of age-related macular degeneration (AMD) presents a significant challenge attributable to high disease heterogeneity. Patient realization of symptoms is poor and it is urgent to treat before permanent anatomic damage results in vision loss. This is true for the initial conversion from non-exudative intermediate AMD (iAMD) to exudative AMD (nAMD), and for the recurrence of nAMD undergoing treatment. Starting from the essential requirements that any practical solution needs to fulfill, we will reflect on how persistent navigation towards innovative solutions during a 25-year journey yielded significant advances towards improvements in personalized care. An early insight was that the acute nature of AMD progression requires frequent monitoring and therefore diagnostic testing should be performed at the patient's home. Four key requirements were identified: (1) A tele-connected home device with acceptable diagnostic performance and a supportive patient user interface, both hardware and software. (2) Automated analytics capabilities that can process large volumes of data. (3) Efficient remote patient engagement and support through a digital healthcare provider. (4) A low-cost medical system that enables digital healthcare delivery through appropriate compensation for both the monitoring provider and the prescribing physician services. We reviewed the published literature accompanying first the development of Preferential Hyperacuity Perimetry (PHP) for monitoring iAMD, followed by Spectral Domain Optical Coherence Tomography (SD-OCT) for monitoring nAMD. Emphasis was given to the review of the validation of the core technologies, the regulatory process, and real-world studies, and how they led to the release of commercial services that are covered by Medicare in the USA. We concluded that while during the first quarter of the 21st century, the two main pillars of management of AMD were anti-VEGF intravitreal injections and in-office OCT, the addition of home-monitoring-based digital health services can become the third pillar.},
}

Humans
*Macular Degeneration/therapy/diagnosis
Telemedicine/trends
Monitoring, Physiologic/methods
Digital Health

@article {pmid41469516,
year = {2025},
author = {Li, D and Ou, Q and Gao, F and Wang, X and Zhu, L and Zhou, Y and Xu, JY and Jin, C and Wang, J and Zhang, J and Li, J and Bi, Y and Lu, L and Xu, GT and Tian, H},
title = {CRX is an intrinsic suppressor of epithelial‒mesenchymal transition in retinal pigment epithelial cells: a promising therapeutic avenue for subretinal fibrosis.},
journal = {Cell death & disease},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41419-025-08352-y},
pmid = {41469516},
issn = {2041-4889},
support = {24ZR1470100//Natural Science Foundation of Shanghai (Natural Science Foundation of Shanghai Municipality)/ ; },
abstract = {The epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells is one of the significant pathogenic mechanisms for the formation of subretinal fibrosis in age-related macular degeneration (AMD). Multiple signaling pathways that promote EMT have been well described, yet the endogenous signaling pathways that inhibit EMT within RPE cells remain largely elusive. In this study, we confirmed the expression of CRX in human RPE cells and human embryonic stem cell-derived RPE (ESC-RPE) cells. By employing sub-culture to disrupt intercellular connections and thereby inhibit the Hippo signaling pathway, combined with TGF-β1 treatment in vitro to mimic the microenvironment for the formation of subretinal fibrosis, it was revealed that Hippo/YAP1 and TGF-β1 synergistically promoted the nuclear translocation of β-catenin, and the latter bound to TCF7 to inhibit the expression of CRX. Overexpression of CRX was capable of suppressing the occurrence of EMT in ESC-RPE cells. CRX exerted its inhibitory effect on EMT partly by upregulating the expression of PPP2R2B. In the laser-induced choroidal neovascularization mouse model, the nuclear translocation of CRX took place in RPE cells, and overexpression of CRX played an inhibitory role in the formation of subretinal fibrosis. This study has identified CRX as an endogenous signaling molecule that inhibits EMT in RPE cells and has provided a new research target and treatment strategy for the treatment of wet AMD and the inhibition of subretinal fibrosis formation.},
}

@article {pmid41469343,
year = {2025},
author = {Fedirko, PA and Babenko, TF and Pilmane, M and Medvedovska, NV and Junga, A and Yaroshenko, ZS and Dorichevska, RY and Garkava, NA},
title = {CURRENT ACHIEVEMENTS AND TOPICAL ISSUES IN RADIATION OPHTHALMOLOGY: POST-CHORNOBYL EXPERIENCE.},
journal = {Problemy radiatsiinoi medytsyny ta radiobiolohii},
volume = {},
number = {30},
pages = {126-142},
doi = {10.33145/2304-8336-2025-30-126-142},
pmid = {41469343},
issn = {2313-4607},
mesh = {*Chernobyl Nuclear Accident ; Humans ; *Cataract/etiology/pathology/epidemiology ; *Radiation Exposure/adverse effects ; *Radiation Injuries/epidemiology/pathology/etiology ; Ukraine/epidemiology ; Radiation, Ionizing ; Occupational Exposure/adverse effects ; *Ophthalmology/trends ; *Eye/radiation effects/pathology ; },
abstract = {The Chornobyl disaster - a largescale nuclear accident that caused significant radiation exposure to large populations of people. The work of ophthalmologists who studied its consequences radically changed scientists' understanding of the effects of ionizing radiation on the organ of vision. Before the Chornobyl accident, it was widely believed that the organ of vision was relatively resistant to the effects of ionizing radiation. It was thought that the most likely effect of radiation exposure was radiation cataracts, which were considered a deterministic effect.The objective of this study is analyze epidemiological, clinical, and experimental data on the ophthalmologicaleffects of radiation obtained after the Chоrnobyl disaster. Materials and methods. The criteria for inclusion in the analytical review were peer reviewed publications in the scientometric databases PubMed/MEDLINE, Scopus, Web of Science, and manually selected works devoted to the study of the ophthalmological consequences of the Chornobyl disaster, other radiation incidents, and the consequences of occupational radiation exposure, published in the period after the Chornobyl disaster.Results. Studies conducted after the Chornobyl disaster have significantly changed the understanding of theeffects of ionizing radiation on the vision organ. It has been shown that the eye is extremely sensitive to radiation exposure and is one of the most vulnerable structures of the body. Analyzing the results of longterm post-Chornobyl studies, we can distinguish four groups of ophthalmological diseases that occur in people affected by the Chornobyl disaster: the first group is specific radiation damage to the eye, the appearance of which is possible only as a result of ionizing radiation exposure; the second group is diseases that under normal conditions occur mainly in elderly people and the development of which is accelerated as a result of radiation exposure; the third group is functional changes that were detected in radiationexposed people; and the fourth group includes effects that occurred in people irradiated in utero.},
}

*Chernobyl Nuclear Accident
Humans
*Cataract/etiology/pathology/epidemiology
*Radiation Exposure/adverse effects
*Radiation Injuries/epidemiology/pathology/etiology
Ukraine/epidemiology
Radiation, Ionizing
Occupational Exposure/adverse effects
*Ophthalmology/trends
*Eye/radiation effects/pathology

@article {pmid41468573,
year = {2025},
author = {Spaide, RF},
title = {Pilot Study of Choroidal Synphlebia.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004755},
pmid = {41468573},
issn = {1539-2864},
abstract = {PURPOSE: To describe the multimodal imaging characteristics and clinical associations of choroidal synphlebia, a newly recognized configuration of the choroidal venous system.

METHODS: This retrospective study analyzed patients imaged with the DREAM swept-source OCT system (Intalight, San Jose, CA), capable of deep choroidal penetration. Choroidal synphlebia was defined as a confluent vascular structure ≥750 µm in smallest lateral or vertical dimension. The multimodal imaging characteristics were evaluated.

RESULTS: Nineteen eyes of sixteen patients (mean age 63.2 years; eight male) were identified. Associated diagnoses included central serous chorioretinopathy (CSC) in 16 eyes, neovascular age-related macular degeneration in 2, and myopia in 1. Three patients had bilateral involvement. Two morphologic patterns were observed: (1) broad confluence of large choroidal veins forming a lobulated venous lake, and (2) a caput medusa-type arrangement with smaller tributaries converging radially into a dilated central channel. The lesions often occurred near presumed choroidal watershed zones. Macular neovascularization was present in 7 eyes. In several CSC cases, subretinal fluid was resistant to photodynamic therapy but responsive to faricimab.

CONCLUSIONS: Choroidal synphlebia represents a distinct choroidal venous phenotype characterized by fusion or coalescence of major veins with a lack of visible vessels in the overlying Sattler's layer and inner choroid. Alterations in the capacitance, resistance, and pressure distribution in the venous drainage system appear to be affected by synphlebia lesions. Recognition of synphlebia may provide insight into choroidal hemodynamics and may help explain atypical or treatment-resistant CSC and neovascular presentations.},
}

@article {pmid41467813,
year = {2026},
author = {Zhu, J and Yu, X and Wen, C and Zhang, Y and Kuang, X and Sun, N and Tang, S and Xiao, B and Xiao, S and Wang, X and Wu, K and Zhang, Q and Shen, H},
title = {Thalidomide Synergistically Regulates Cell Cycle and Endoplasmic Reticulum Stress to Alleviate RPE Oxidative Damage Through the E2F2-FBXO5 Pathway.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {40},
number = {1},
pages = {e71387},
doi = {10.1096/fj.202502444R},
pmid = {41467813},
issn = {1530-6860},
support = {2024A1515013099//GDSTC | Natural Science Foundation of Guangdong Province ()/ ; 2024A03J0264//Scientific and Technological Planning Project of Guangzhou City ()/ ; 2025QZLH06//State Key Laboratory of Ophthalmology (SKLO)/ ; },
mesh = {*Endoplasmic Reticulum Stress/drug effects ; Animals ; *Oxidative Stress/drug effects ; *Thalidomide/pharmacology ; Mice ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; Humans ; Signal Transduction/drug effects ; *E2F2 Transcription Factor/metabolism ; *Cell Cycle/drug effects ; Mice, Inbred C57BL ; Macular Degeneration/metabolism/drug therapy/pathology ; Male ; },
abstract = {Thalidomide, a glutamate derivative with teratogenicity, possesses anti-inflammatory, immunomodulatory, and anti-angiogenic properties that enable its use in treating refractory diseases unresponsive to conventional therapies. Dry age-related macular degeneration (AMD), characterized by retinal pigment epithelium (RPE) degeneration and lacking effective therapies, represents a significant unmet medical need. Our findings demonstrated that thalidomide significantly restores mitochondrial function, alleviates G2/M phase cell cycle arrest, and suppresses sustained endoplasmic reticulum (ER) stress in oxidatively injured RPE cells. Mechanistically, these effects are coordinated through E2F2 activation, which subsequently regulates FBXO5 expression. Moreover, thalidomide was able to ameliorate oxidative stress-induced retinal structural disorders and RPE degeneration, and improve visual function in mice. In summary, this study elucidates that thalidomide synergistically regulates cell cycle progression and endoplasmic reticulum homeostasis through the E2F2-FBXO5 signaling pathway, providing a new drug candidate and therapeutic target for the prevention and treatment of dry AMD.},
}

*Endoplasmic Reticulum Stress/drug effects
Animals
*Oxidative Stress/drug effects
*Thalidomide/pharmacology
Mice
*Retinal Pigment Epithelium/metabolism/drug effects/pathology
Humans
Signal Transduction/drug effects
*E2F2 Transcription Factor/metabolism
*Cell Cycle/drug effects
Mice, Inbred C57BL
Macular Degeneration/metabolism/drug therapy/pathology
Male