@article {pmid41353467,
year = {2025},
author = {E de Carlo Forest, T and Marin, AI and Gill, Z and Gnanaraj, R and Patnaik, JL and Poppelaars, F and Lynch, AM and Palestine, AG and Mathias, MT and Manoharan, N and Frazer-Abel, AA and Holers, VM and Mandava, N},
title = {Association between systemic complement levels and choroidal thickness in advanced non-neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-31051-9},
pmid = {41353467},
issn = {2045-2322},
support = {R01EY032456//U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)/ ; UL1 TR002535/TR/NCATS NIH HHS/United States ; },
abstract = {To investigate associations between systemic complement activation and choroidal thickness (CT) in advanced non-neovascular age-related macular degeneration (nnAMD). Cross-sectional study of 96 patients (187 eyes) with advanced nnAMD enrolled in the University of Colorado AMD Registry (August 2014-June 2021). Medical histories, multimodal imaging, and plasma samples were collected. Plasma was analyzed via enzyme-linked immunosorbent assay and multiplex Luminex assays for complement factors C1q, monoclonal B-cell lymphocytosis, C2, C4, C4b, C3, C3a, Factor B, Bb, Factor D, Factor H, Factor I, C5 and soluble C5b-9. CT was measured subfoveally and at 1000 μm intervals superiorly, inferiorly, nasally, and temporally using Spectralis OCT. Linear modeling with generalized estimating equations assessed log-transformed OCT and complement factors. The mean age was 82.2 years (± 7.1 SD); 54.2% were female. Average CT was negatively associated with Bb (β=-0.47, SE: 0.12, p = 0.0001) and the Bb/Factor B ratio (β=-0.28, SE: 0.12, p = 0.02), but not other complement markers. Bb levels correlated with alternative pathway components but not with classical or lectin pathway markers. We found a key association between systemic complement activation of Factor B and choroidal thickness in patients with advanced nnAMD, implying the potential involvement of the systemic alternative pathway in nnAMD patients.},
}

@article {pmid41352581,
year = {2025},
author = {Dinah, C and Esmaeelpour, M and Rachitskaya, AV and De Salvo, G and Munk, MR},
title = {Functional endpoints in patients with geographic atrophy: What to consider when designing a clinical trial.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101421},
doi = {10.1016/j.preteyeres.2025.101421},
pmid = {41352581},
issn = {1873-1635},
abstract = {There is an unmet need in patients with geographic atrophy (GA) for treatments that preserve and improve functional vision to maintain their independence and quality of life. The limited number of available treatments for GA have demonstrated structural benefits, but none have consistently shown significant functional outcomes in clinical trials. Currently, best-corrected visual acuity (BCVA) is considered the gold standard functional endpoint in clinical trials; however, in the case of GA, it cannot fully evaluate visual impairment or treatment response, particularly in fovea-sparing GA lesions. In addition, BCVA may not fully capture the functional impact of foveal and parafoveal scotomas. There is emerging evidence for the utility of other functional assessments that may provide a more robust representation of the functional impact of GA; however, the current utilization of these tests in GA clinical trials varies widely. This review aims to evaluate current functional endpoints in GA and their strengths and limitations based on characteristics such as strength of structure-function correlation, practicality and feasibility, and patient perspective. There are many factors to consider when choosing a functional vision assessment when designing a GA clinical trial, and each functional vision assessment has several advantages and disadvantages, which are summarized in this review article.},
}

@article {pmid41352549,
year = {2025},
author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Wang, X},
title = {SS-OCTA versus ICGA: A Comparison of Detection Efficiency for Large Choroidal Vein Patterns in AMD Patients.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105303},
doi = {10.1016/j.pdpdt.2025.105303},
pmid = {41352549},
issn = {1873-1597},
abstract = {PURPOSE: To compare the efficacy of swept-source optical coherence tomography angiography (SS-OCTA) and indocyanine green angiography (ICGA) in visualizing and classifying large choroidal vein topography, and to evaluate the association between specific venous patterns and pachychoroid spectrum disease (PSD)-associated macular neovascularization (MNV).

METHODS: This retrospective cross-sectional study included 222 eyes from 160 patients with neovascular age-related macular degeneration (nAMD). All participants underwent both SS-OCTA and ICGA imaging. Choroidal venous patterns were classified into four types based on ICGA venous phase images: watershed, anastomotic, upper thicker, and lower thicker. SS-OCTA images were processed and analyzed using Fiji software. Diagnostic agreement between modalities was assessed using Cohen's Kappa. Logistic regression was used to evaluate the association between venous patterns and disease subtypes.

RESULTS: SS-OCTA and ICGA showed almost perfect agreement in classifying choroidal venous patterns in discernible cases (unweighted Kappa = 0.978). Among 77 eyes where ICGA failed to provide a clear classification, SS-OCTA achieved a definitive diagnosis in 87.0% (P < 0.001), with the anastomotic type being the most common. Furthermore, the watershed pattern was significantly more prevalent in non-PCV nAMD compared to PCV (29.8% vs. 12.1%, p = 0.002), suggesting distinct choroidal venous backgrounds between these subtypes.

CONCLUSION: SS-OCTA provides a reliable, non-invasive alternative to ICGA for visualizing and classifying large choroidal veins, with superior performance in cases obscured by hemorrhage or leakage. The distinct distribution of venous patterns across nAMD subtypes highlights the potential role of choroidal venous architecture in disease phenotyping and pathogenesis.},
}

@article {pmid41352547,
year = {2025},
author = {Wang, N and Liu, X and Wu, J and Xiang, X and Gao, Y and Yao, L and Zhang, S},
title = {Multimodal and 3D Imaging Presentation of the Evolution of Pressure-Related CNV.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105305},
doi = {10.1016/j.pdpdt.2025.105305},
pmid = {41352547},
issn = {1873-1597},
abstract = {This study reports a unique case that visually demonstrates the six-year evolution of a pressure-related choroidal neovascularization (CNV) using multimodal image registration and three-dimensional (3D) reconstruction. A 65-year-old female with neovascular age-related macular degeneration received 33 anti-VEGF injections over six years but experienced continued vision decline. Through precise registration of indocyanine green angiography, and optical coherence tomography angiography images, combined with 3D modeling of swept-source OCTA volume data. We found that the main trunk of this large, tree-like type II CNV originated from an abnormally dilated great vein, which exhibited an anastomosis with an accompanying great vein. Furthermore, the 3D reconstruction viewed from the scleral side revealed that this vein was closely opposed to and shared a shunt branch with an underlying choroidal great artery. The CNV appeared to function as a "pressure-relief valve," sprouting from the venous trunk to alleviate pressure. This case underscores the critical role of deep multimodal imaging integration in tracing CNV origins and reveals that some anti-VEGF-resistant CNVs may represent hemodynamic compensatory disorders secondary to pre-existing large vessel structural abnormalities, rather than purely neovascular diseases.},
}

@article {pmid41350762,
year = {2025},
author = {Ma, Y and Zan, H and Li, L and Li, S and Yu, X and Li, J and Cai, J and Zhang, H and Yang, J and Zhang, R and Salvi, R and Li, W and Wang, H and Yin, S},
title = {Global burden and geospatial drivers of sensory impairment with sense organ disease projections to 2050.},
journal = {Communications medicine},
volume = {},
number = {},
pages = {},
doi = {10.1038/s43856-025-01259-x},
pmid = {41350762},
issn = {2730-664X},
support = {82271161//National Natural Science Foundation of China (National Science Foundation of China)/ ; 82330034//National Natural Science Foundation of China (National Science Foundation of China)/ ; },
abstract = {BACKGROUND: Sense organ diseases represent the leading causes of years lived with disability. Despite its major impact, a comprehensive understanding of sense organ diseases burden remains limited.

METHODS: Based on the data from the Global Burden of Disease Study 2021 and nighttime light exposure data from remote-sensing satellites, we did secondary analysis and described the epidemiological characteristics of sense organ diseases globally and nationally. The relationship between the specific causes of blindness and vision loss and nighttime light exposure was further explored. We assessed the trends, causes and cross-country inequalities related to sense organ diseases and forecasted the burden of disease until 2050.

RESULTS: Here we show that in 2021, there are more than 2 billion prevalent cases and more than 77 million years lived with disability cases of sense organ diseases globally. Both age-related macular degeneration and near vision loss show positive correlations with nighttime light exposure. The global burden of sense organ diseases continues to rise from 1990 to 2021, primarily driven by population growth and ageing. Health inequalities exist between different countries and increase over time. Projections of years lived with disability for sense organ diseases from 2022 to 2050 show that although the age-standardized rate remains stable, the number increases significantly.

CONCLUSIONS: Over the past 32 years, the global burden of sense organ diseases has increased, and cross-country inequalities have intensified due to the trends of population growth and aging. Therefore, it is urgently necessary to formulate more targeted and effective prevention and management strategies.},
}

@article {pmid41350718,
year = {2025},
author = {Ruiz-Medrano, J and Pana, I and García-Zamora, M and Flores-Moreno, I and Puertas, M and Ruiz-Moreno, JM},
title = {Faricimab treat-and-extend approach for neovascular age-related macular degeneration: insights from real-world clinical practice.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00776-0},
pmid = {41350718},
issn = {2056-9920},
abstract = {PURPOSE: To evaluate the clinical outcomes of the switch to faricimab in a treat-and-extend (T&E) regimen patients with neovascular age-related macular degeneration (nAMD).

METHODS: This prospective cohort study included consecutive patients with nAMD who had previously been treated with anti-VEGF agents in a T&E regimen, with treatment intervals (TI) that could not be extended beyond 12 weeks, and a minimum follow-up of 24 weeks. These patients were switched to faricimab therapy in a T&E regimen for at least 6 months. The primary endpoint was the TI between intravitreal injections (IVIs), and the secondary endpoint was the mean change in best-corrected visual acuity (BCVA) from baseline to the last follow-up visit (LFUV).

RESULTS: A total of 225 eyes from 188 patients were included, with a mean age of 79.6 ± 7.4 years. Previous anti-VEGF treatments included ranibizumab (n = 34), aflibercept (n = 144), brolucizumab (n = 6), and bevacizumab (n = 41). TI1 (5.9 ± 2.0 weeks) matched the prior treatment interval. Significant increases in treatment intervals were observed at subsequent time points (TI2: 8.2 ± 3.2 weeks, TI3: 10.1 ± 3.9 weeks, TI4: 10.7 ± 4.3 weeks, TI5: 9.9 ± 4.0 weeks, and TI6: 8.5 ± 4.4 weeks; p < 0.001). BCVA remained stable, going from 0.41 ± 0.23 to 0.43 ± 0.24 (p = 0.0112). The mean number of injections was 5.9 ± 1.9, with a mean follow-up duration of 51.4 ± 11.8 weeks.

CONCLUSIONS: The switch to faricimab in a T&E regimen significantly increased treatment intervals maintaining BCVA in patients with nAMD under other anti-VEGF treatments. No serious adverse events were reported. Longer follow-up is needed to confirm these results.},
}

@article {pmid41349782,
year = {2025},
author = {Horrigan, WF and Caron, Q and Rodriguez, A and Singh, R and Anand-Apte, B},
title = {The Effect of Age on Wound Healing in the Laser Induced Choroidal Neovascularization Model.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110790},
doi = {10.1016/j.exer.2025.110790},
pmid = {41349782},
issn = {1096-0007},
abstract = {The laser induced model of choroidal neovascularization (LiCNV) is a commonly used in vivo rodent model to study neovascular age-related macular degeneration (nAMD), although progression of this model is not well understood. In this study we characterize and compare the longitudinal progression of wound healing of laser induced choroidal neovascular (CNV) lesions in young and old mice. Using 2-month and 12-month-old C57BL/6J mice and ocular computerized tomography (OCT), fluorescein and indocyanine green angiography we performed a longitudinal imaging analysis at 3-, 7-, 14- and 28-days following laser injury. This was compared with immunohistochemical analysis of the lesions at similar timepoints for markers of angiogenesis, fibrosis, epithelial-to-mesenchymal transition (EMT), and gliosis. OCT analysis determined an increased lesion volume in older mice. In contrast younger mice demonstrated earlier vascularization and fibrosis with no difference in neovascularization or leakage. Reactive gliosis occurs directly above the laser-induced CNV lesion in both ages. The RPE in this model encloses the lesion area by day 14 in both young and old mice. This study concludes that age is an important variable in some but not all aspects of laser-induced CNV.},
}

@article {pmid41348407,
year = {2025},
author = {Hang, Z and Li, Y and Ren, W and Du, H},
title = {The blood-retinal barrier in ocular pathologies: an updated narrative review.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {10},
pmid = {41348407},
issn = {1573-2630},
mesh = {Humans ; *Blood-Retinal Barrier/physiopathology/pathology ; *Retinal Diseases/physiopathology ; *Eye Diseases/physiopathology ; },
abstract = {PURPOSE: To provide a comprehensive overview of the structural and functional characteristics of the blood-retinal barrier (BRB), examine its critical role in the pathogenesis of major ocular diseases, and summarize current and emerging therapeutic strategies aimed at restoring BRB integrity.

METHODS: A literature search was conducted in PubMed, Scopus, and Web of Science databases, focusing primarily on publications from the past 10 years supplemented by seminal earlier works. This narrative review synthesizes evidence on BRB molecular anatomy, pathological mechanisms, disease-specific roles, and therapeutic interventions.

RESULTS: The BRB comprises inner (iBRB) and outer (oBRB) compartments with distinct cellular and molecular architectures. BRB dysfunction is driven by convergent mechanisms including aging, hyperglycemia, oxidative stress, inflammation, and hypoxia, which disrupt tight junction proteins and promote aberrant angiogenesis. This barrier breakdown constitutes a pivotal pathogenic driver in major blinding diseases: age-related macular degeneration, diabetic retinopathy and retinal vein occlusion, glaucoma, and uveitis. Current standard treatments include anti-VEGF agents and corticosteroids. Emerging strategies target Wnt/β-catenin signaling, employ senolytic therapies, utilize biomaterial-based drug delivery, and develop organ-on-a-chip models for personalized medicine.

CONCLUSIONS: BRB disruption represents a critical inflection point in ocular disease progression, triggering self-perpetuating cycles of neuroinflammation and degeneration. Effective restoration requires multi-faceted approaches combining anti-angiogenic, antiinflammatory, and barrier-strengthening mechanisms. Future research should focus on dynamic functional assessment, single-cell multi-omics integration, and adaptive therapeutic strategies to prevent irreversible vision loss.},
}

Humans
*Blood-Retinal Barrier/physiopathology/pathology
*Retinal Diseases/physiopathology
*Eye Diseases/physiopathology

@article {pmid41348378,
year = {2025},
author = {Wang, S and Hong, Y and Qu, Y and Zheng, K and Luo, H and Chen, R and Jia, H and Liu, X and Sun, X},
title = {Association between low handgrip strength and the increased risk of age-related macular degeneration: results from UK biobank cohort study.},
journal = {Aging clinical and experimental research},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40520-025-03208-z},
pmid = {41348378},
issn = {1720-8319},
abstract = {OBJECTIVES: To determine whether handgrip strength is associated with the incidence of age-related macular degeneration.

METHODS: A prospective cohort study of over 500 thousand UK Biobank participants aged 40-69 years. Individuals ≥ 50 years and without age-related macular degeneration at baseline were included. Exposure was the handgrip strength measured by dynamometer. Primary outcome was the incidence of age-related macular degeneration during 13 years of follow-up. Cox proportional-hazard models were fitted to estimate the risk effect for handgrip strength on age-related macular degeneration, and stratified for sociodemographic and lifestyle factors. Mediation models were regressed to explore underlying mechanisms driven by inflammatory and erythrocyte-related biomarkers.

RESULTS: 382174 eligible participants in the UK Biobank were included. After 4680431 person-year, 7987 individuals (2.09%) developed age-related macular degeneration. Individuals in the lowest quintile of handgrip strength had higher risk of age-related macular degeneration incidence (Hazard Ratio, 1.25; 95% CI, 1.16-1.35) compared with those in the highest quintile. Per 5 kg decrement in handgrip strength was associated with increased risk of age-related macular degeneration incidence (Hazard Ratio, 1.06; 95% CI, 1.04-1.08) with similar trend among all subgroups except for sex. Specific inflammatory and erythrocyte-related biomarkers partially (37.5%) mediated the incidence of age-related macular degeneration as substantial biological mechanisms following handgrip strength decrease.

CONCLUSIONS: Our findings suggest that handgrip strength is associated with the incidence of age-related macular degeneration under the mediation of systemic proinflammatory factors. The current study holds an outlook for improved visual health over the evaluation and intervention of muscle strength in old-age population.},
}

@article {pmid41348248,
year = {2025},
author = {Bartol-Puyal, FA and Sánchez Monroy, J and Puzo Bayod, M and Mallén, V and Méndez-Martínez, S and Calvo, P and Pablo, L},
title = {Choroidal changes after antiVEGF in neovascular age-related macular degeneration with type 1 and 3 macular neovascularization.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {8},
pmid = {41348248},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; Male ; *Choroid/pathology ; Tomography, Optical Coherence/methods ; Female ; *Angiogenesis Inhibitors/administration & dosage ; Aged ; Intravitreal Injections ; *Wet Macular Degeneration/drug therapy/diagnosis ; Fluorescein Angiography/methods ; Aged, 80 and over ; Visual Acuity ; Follow-Up Studies ; Fundus Oculi ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Ranibizumab/administration & dosage ; *Bevacizumab/administration & dosage ; Middle Aged ; *Choroidal Neovascularization/drug therapy/diagnosis ; },
abstract = {PURPOSE: To analyze choroidal thickness (CT) in patients with neovascular age-related macular degeneration (nAMD) with type 1 macular neovascularization (MNV) and type 3 (or retinal angiomatous proliferation) after antiVEGF treatment for two years.

METHODS: Retrospective study enrolling Caucasian naïve patients with nAMD (type 1 MNV), and patients with type 3 MNV with no other ophthalmological disorders, and without switching treatment. Nine manual CT measurements were performed on optical coherence tomography (OCT) Spectralis (Heidelberg Engineering). Demographic data, smoking, disease activity, and number of injections, among others were recorded. Three visits were analyzed: pretreatment baseline visit, first and last visits with no disease activity.

RESULTS: 53 eyes of 53 patients with type 1 MNV, and 41 eyes of 41patients with type 3 MNV were analyzed. Both groups received the same number of injections (p = 0.282). Type 3 MNV patients showed lower CT (between 143.29 and 174.17μm) than type 1 MNV patients (between 169.91 and 220.17μm) in the baseline visit, but differences disappeared in first and last visits. Choroidal thinning was only observed in type 1 MNV patients between baseline and first visit (p < 0.05). In the las visit, they had a CT between 87 and 96% of baseline measurement. No other influencing factor was detected.

CONCLUSIONS: Patients with nAMD (type 1 MNV) have higher CT than patients with type 3. However, patients with type 1 MNV experience significant choroidal thinning, and CT is similar in both groups after antiVEGF treatment. Smoking, type of drusen or other OCT features have no influence in this reduction.},
}

Humans
Retrospective Studies
Male
*Choroid/pathology
Tomography, Optical Coherence/methods
Female
*Angiogenesis Inhibitors/administration & dosage
Aged
Intravitreal Injections
*Wet Macular Degeneration/drug therapy/diagnosis
Fluorescein Angiography/methods
Aged, 80 and over
Visual Acuity
Follow-Up Studies
Fundus Oculi
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Ranibizumab/administration & dosage
*Bevacizumab/administration & dosage
Middle Aged
*Choroidal Neovascularization/drug therapy/diagnosis

@article {pmid41347874,
year = {2025},
author = {Trivizki, O and Wykoff, CC and Smoor, MA and Rabinovitch, D and Zhou, A and Cao, JA and Lechanteur, YTE and van den Heuvel, L and van Gool, AJ and Gloerich, J and Vergroesen, JE and Klaver, CCW},
title = {Effect of Pegcetacoplan on Aqueous Humor Proteome in Geographic Atrophy: A Prospective Exploration.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {24},
doi = {10.1167/iovs.66.15.24},
pmid = {41347874},
issn = {1552-5783},
mesh = {Humans ; *Aqueous Humor/metabolism ; *Geographic Atrophy/drug therapy/metabolism ; Prospective Studies ; Male ; Aged ; Female ; *Proteome/metabolism/drug effects ; Tandem Mass Spectrometry ; Chromatography, Liquid ; Complement C3/antagonists & inhibitors ; Proteomics/methods ; Aged, 80 and over ; Middle Aged ; },
abstract = {PURPOSE: Pegcetacoplan, a complement component 3 (C3) inhibitor, has recently received U.S. Food and Drug Administration approval for treating geographic atrophy (GA), an advanced stage of age-related macular degeneration (AMD). However, the limited treatment response prompts further investigations into its molecular effects.

METHODS: We prospectively collected aqueous humor (AH) samples from 11 patients with GA before and at 2 months during pegcetacoplan treatment. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) was used to analyze the proteome, and global normalization was applied to account for differences in protein concentration. To assess global proteomic shifts over time, principal component analysis (PCA) was performed. The Friedman test was used to assess differences in protein intensities across time points while adjusting for multiple testing using Benjamini-Hochberg false discovery rate (FDR) correction.

RESULTS: A total of 283 proteins were analyzed. PCA revealed temporal changes in global protein expression profiles, with a significant shift between baseline and month 2 (P = 0.01). The levels of complement components C3 (P = 0.12) and C5 (P = 0.27) remained stable after initiation of treatment, but the levels of C1qB, C1RL, C2, C6, C7, C8, C9, factor D, factor H, and factor I increased significantly (all P < 0.05). Most non-complement proteins showed no significant changes; however, beta-2-glycoprotein 1 (FDR = 0.09), kininogen 1 (FDR < 0.05), and prothrombin (FDR < 0.05) increased significantly, and kallistatin (FDR < 0.05) and plasma serine protease inhibitor (FDR < 0.05) decreased.

CONCLUSIONS: This exploratory study suggests that pegcetacoplan modulates the AH proteome in GA. Although no changes in the target protein C3 were detected following treatment, significant changes in proteins tightly connected to complement, inflammation, and coagulation were observed. These findings underscore the need for further investigation into the biological and clinical relevance of the observed molecular shifts.},
}

Humans
*Aqueous Humor/metabolism
*Geographic Atrophy/drug therapy/metabolism
Prospective Studies
Male
Aged
Female
*Proteome/metabolism/drug effects
Tandem Mass Spectrometry
Chromatography, Liquid
Complement C3/antagonists & inhibitors
Proteomics/methods
Aged, 80 and over
Middle Aged

@article {pmid41346473,
year = {2025},
author = {Buscaglia, M and Gouriou, B and Asquoët, Y and Le Goïc, N and Le Grand, F and Hachem, M and Soudant, P},
title = {Production of [13]C-labeled docosahexaenoic acid from heterotrophic marine microorganisms Aurantiochytrium mangrovei and Crypthecodinium cohnii enabling fluxomic applications.},
journal = {Frontiers in bioengineering and biotechnology},
volume = {13},
number = {},
pages = {1690863},
pmid = {41346473},
issn = {2296-4185},
abstract = {Docosahexaenoic acid (DHA, 22:6n-3) is the predominant polyunsaturated fatty acid in the human brain and eyes, playing a crucial role in vision and cognitive development. DHA deficiency has been associated with ocular diseases, such as macular degeneration and glaucoma, as well as neurodegenerative disorders. Since the human body has a limited ability to synthesize DHA from its precursor, alpha-linolenic acid (ALA, 18:3n-3), targeted DHA supplementation is essential for these patients. To investigate DHA metabolism and integration, researchers commonly use stable ([2]H,[13]C) or radioactive ([3]H,[14]C) isotopes, which are expensive and not widely accessible, restricting the scope and duration of studies. This study aimed to develop a sustainable method for biosynthesizing uniformly labeled [13]C-DHA by culturing the heterotrophic protists Aurantiochytrium mangrovei and Crypthecodinium cohnii with [13]C-glucose. The major fatty acids (FA) of A. mangrovei included 16:0, 22:5n-6 (DPA), and DHA, with DHA accounting for 50.5% ± 4.9% of the total FA. Gas Chromatography-Mass Spectrometry (GC-MS) analysis revealed a[13]C-enrichment of DHA at 96.7% ± 0.4% after the effective High Performance Liquid Chromatography (HPLC) purification. The predominant FA of C. cohnii were 12:0, 14:0, 16:0, and DHA, with DHA representing around 27% of the total FA and exhibiting a[13]C-enrichment of 86.3% ± 1.6%. Based on FA content, A. mangrovei showed a balanced distribution of neutral and polar lipids, with DHA predominantly in the polar fraction (57.8% ± 3.1%), whereas C. cohnii exhibited a predominance of neutral lipids (82.4% ± 0.3%), which contained the majority of its DHA (57.5% ± 1.0%).},
}

@article {pmid41345313,
year = {2025},
author = {Niknahad, A and Zielińska, A and Auffarth, GU and Son, HS and Lee, H and Khoramnia, R and Łabuz, G},
title = {[Emerging technology for retinal function testing: two-photon microperimetry].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41345313},
issn = {2731-7218},
abstract = {The technique of 2‑photon microperimetry is an emerging procedure that combines measurement of retinal sensitivity with retinal imaging and offers substantial improvements compared to conventional microperimetry. Conventional microperimetry relies on 1‑photon linear absorption while 2‑photon microperimetry relies on the simultaneous absorption of two photons, leading to enough energy for photoisomerization of visual pigments and perception of colors, such as green. This 2‑photon absorption process has shown a lower spread of measurements at one retinal location, leading to more reproducible data compared to conventional microperimetry. The current literature also suggests that 2‑photon microperimetry provides more reliable measurements in the presence of lens opacities, a common issue in an aging eye. Furthermore, it has been successfully utilized to assess retinal function in patients with diabetic retinopathy, age-related macular degeneration and glaucomatous neuropathy. These advantages highlight the very promising application in clinical settings. Future adjustments focusing on implementing this technology in the clinical practice could improve outcomes in the early detection and monitoring of retinal diseases.},
}

@article {pmid41344859,
year = {2025},
author = {Schmidt, I and Volkmer, P and Müskens, RPHM and van der Waaij, AM and van Dam, GM and Huiskamp, EA and Nagengast, WB},
title = {Targeted Fluorescence Imaging of Bevacizumab-800CW in Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Journal of nuclear medicine : official publication, Society of Nuclear Medicine},
volume = {},
number = {},
pages = {},
doi = {10.2967/jnumed.125.270802},
pmid = {41344859},
issn = {1535-5667},
abstract = {The purpose of this study was to determine the safety and feasibility of fluorescence molecular imaging using a commercially available system and intravenous injection of fluorescently labeled bevacizumab (bevacizumab-800CW) to visualize bevacizumab distribution in patients with neovascular age-related macular degeneration (nAMD)s. Methods: Twelve patients with active nAMD aged 60 y or older, who were either on anti-vascular endothelial growth factor (VEGF) therapy or were anti-VEGF therapy naïve, received an intravenous injection of 4.5 mg (n = 3) or 15 mg (n = 9) of bevacizumab-800CW. This clinical trial was divided into 2 parts. An interim analysis was performed after the inclusion of 3 patients per dose group (study part 1) to determine the more optimal dose. Then 6 additional patients were included with the optimal dose in study part 2. All patients underwent standard clinical imaging, including fundus photography, optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. Fluorescence imaging was performed 1 min, 60 min, and 3-4 d after bevacizumab-800CW injection. Results: Bevacizumab-800CW injections were safe and well tolerated. One minute after injection, only the 15-mg group demonstrated a significantly higher contrast-to-noise ratio (median, 6.32) in vessels compared with baseline (median, -4.44; P = 0.0342). This, combined with the clear visual uptake after 3-4 d, supported 15 mg as the preferred dose. Contrast-to-noise ratio values inside the macula of patients receiving 15 mg of bevacizumab-800CW (n = 8) were significantly higher after 3-4 d (median, 4.45) compared with baseline (median, 0.19; P = 0.0078). Conclusion: Targeted fluorescent tracers such as bevacizumab-800CW can visualize VEGF expression, providing important insights into nAMD, and can pave the way toward personalized treatments and targeted drug development.},
}

@article {pmid41343426,
year = {2025},
author = {DeLucia, PR and Oberfeld, D and Kearney, JK and Cloutier, M and Jilla, AM and Zhou, A and Corona, ST and Cormier, J and Taylor, A and Wykoff, CC and Baurès, R},
title = {Visual, auditory, and audiovisual time-to-collision estimation among participants with age-related macular degeneration compared to a normal-vision group: The TTC-AMD study.},
journal = {PloS one},
volume = {20},
number = {12},
pages = {e0337549},
doi = {10.1371/journal.pone.0337549},
pmid = {41343426},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/physiopathology ; Male ; Female ; Aged ; *Visual Perception/physiology ; *Auditory Perception/physiology ; Aged, 80 and over ; Middle Aged ; Cues ; *Vision, Ocular ; },
abstract = {Little is known about whether and to what degree people with different amounts of visual impairment rely on hearing instead of vision for mobility, particularly in judgments of collision. We measured how much importance was assigned to visual and auditory cues during time-to-collision judgments made by people with age-related macular degeneration (Impaired Vision Group; IV) compared to a control group without age-related macular degeneration (Normal Vision Group; NV). A virtual reality system simulated a roadway with an approaching vehicle viewed from the perspective of a pedestrian. Participants pressed a button to indicate the time the vehicle would reach them. The vehicle was presented visually only, aurally only, or both simultaneously. Standardized regression coefficients and general dominance weights indicated that time-to-collision (TTC) judgments were determined by both auditory and visual cues in both groups. In the vision-only modality condition, the relative importance of distance and optical size compared to TTC was higher in the IV group compared to the NV group, but with a relatively small effect size. In all modality conditions, the mean absolute error of TTC estimates was comparable between groups, and a multimodal advantage was not observed. Intraindividual variability was greater in the IV group only in the AV condition. The implication is that similar performance can be achieved through the use of different sources of information. Importantly, people with and without IV achieved similar performance but showed differences in the relative importance of different sensory sources of information. A comparison of two IV subgroups differing in severity suggested that simply having IV in both eyes is not sufficient to predict TTC estimation differences between people with IV and people without IV who have normal vision. Rather it appears to be the degree of bilateral visual impairment of the IV that matters.},
}

Humans
*Macular Degeneration/physiopathology
Male
Female
Aged
*Visual Perception/physiology
*Auditory Perception/physiology
Aged, 80 and over
Middle Aged
Cues
*Vision, Ocular

@article {pmid41342744,
year = {2025},
author = {Cakici, O and Yilmaz, OF and Karaca, S and Sarmis, A and Mutlu, MA and Sahin, ZB and Borucu, B and Oguz, H},
title = {Conjunctival Microbiota in retinal diseases requiring anti-VEGF therapy: Age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251393397},
doi = {10.1177/11206721251393397},
pmid = {41342744},
issn = {1724-6016},
abstract = {PurposeThis study aimed to investigate the conjunctival microbiota of patients requiring intravitreal injections due to diabetic retinopathy (DR), age-related macular degeneration (AMD), and retinal vein occlusion (RVO).MethodsA total of 182 participants (46 DR, 71 AMD, 16 RVO, and 49 controls) were enrolled between August and November 2024. Conjunctival swabs were collected from both eyes under sterile conditions prior to injection and cultured on 5% sheep blood and chocolate agar. Microorganisms were identified using Vitek MS.ResultsNo significant differences were observed among the groups in overall microbial growth frequency (all p > 0.05). Gram-negative bacteria, fungi, and polymicrobial growth were more frequently detected in DR and AMD patients, suggesting a trend toward greater microbial diversity, although these differences were not statistically significant.ConclusionDR and AMD patients exhibited higher prevalence of gram-negative, fungal, and polymicrobial colonization. These findings underscore the importance of strict aseptic preparation, povidone-iodine disinfection, and targeted prophylactic strategies to minimize post-injection infection risk in high-risk populations.},
}

@article {pmid41342623,
year = {2025},
author = {Peter, VG and Hayoz, M and Scandella, D and Sznitman, R and Escher, P and Zinkernagel, MS},
title = {AI-Assisted Optical Coherence Tomography Segmentation for Enhanced Diagnosis of Inherited Retinal Diseases.},
journal = {Translational vision science & technology},
volume = {14},
number = {12},
pages = {8},
doi = {10.1167/tvst.14.12.8},
pmid = {41342623},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; *Retinal Diseases/diagnosis/diagnostic imaging/genetics ; *Artificial Intelligence ; Male ; Female ; Middle Aged ; Aged ; Algorithms ; Adult ; Macular Degeneration/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Retina/diagnostic imaging ; },
abstract = {PURPOSE: Inherited retinal diseases (IRDs) are rare and diverse, posing a diagnostic challenge in ophthalmology. This study aimed to determine whether artificial intelligence (AI)-assisted image processing can improve IRD diagnosis and provide insights into disease characteristics. We used an optical coherence tomography (OCT) segmentation algorithm to characterize retinal features in IRDs. Two control groups were included to enhance the contextual understanding of these features: healthy eyes and eyes with age-related macular degeneration (AMD). An AI-driven classification model was then used to classify the data into disease and control groups.

METHODS: We analyzed 327 images from 181 patients with IRD and 146 control individuals, including healthy subjects and patients with AMD. IRD cases were stratified into macular and retinal dystrophies. Automated segmentation of six retinal layers and detection of nine biomarkers were performed on retinal OCT images using the AI-based RetinAI Discovery tool. A random forest classifier differentiated macular IRD, retinal IRD, and controls.

RESULTS: The model detected IRD with 91% accuracy and achieved 91% accuracy in differentiating macular from retinal IRD. Key OCT features for differentiation included reduced perifoveal photoreceptor and outer nuclear layer thicknesses and increased retinal nerve fiber layer thickness in retinal IRD. Macular IRD featured significant foveal photoreceptor and outer nuclear layer thinning.

CONCLUSIONS: This study shows that standardized OCT image analysis combined with AI-based classification can accurately detect and stratify IRDs. The model's high accuracy highlights its potential as a reliable diagnostic tool in ophthalmology.

TRANSLATIONAL RELEVANCE: This AI-assisted OCT evaluation approach enhances ophthalmic diagnostics by improving IRD detection and classification.},
}

Humans
*Tomography, Optical Coherence/methods
*Retinal Diseases/diagnosis/diagnostic imaging/genetics
*Artificial Intelligence
Male
Female
Middle Aged
Aged
Algorithms
Adult
Macular Degeneration/diagnostic imaging
*Image Processing, Computer-Assisted/methods
Retina/diagnostic imaging

@article {pmid41342587,
year = {2025},
author = {Zhao, S and Voegele, F and Tang, J and Clark, SJ and Tschulakow, AV and Julien, S},
title = {Time Course of Structural, Functional, Complement Changes and Inflammatory Processes in a Sodium Iodate Rat Model of Geographic Atrophy.},
journal = {FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
volume = {39},
number = {23},
pages = {e71307},
doi = {10.1096/fj.202502226R},
pmid = {41342587},
issn = {1530-6860},
support = {//Dr. Werner Jackstaedt Stiftung, Germany/ ; //Guangzhou Elites Scholarship Council, China/ ; //Open access Publishing Fund of University of Tuebingen/ ; },
mesh = {Animals ; *Geographic Atrophy/chemically induced/pathology/metabolism ; *Iodates/toxicity ; Rats ; Disease Models, Animal ; Rats, Long-Evans ; Retinal Pigment Epithelium/pathology/metabolism ; *Inflammation/pathology/metabolism/chemically induced ; Tomography, Optical Coherence ; Electroretinography ; Male ; },
abstract = {Geographic atrophy (GA) is characterized by the loss of choriocapillaris, retinal pigment epithelium (RPE) and photoreceptors and is an advanced form of age-related macular degeneration (AMD)-a leading cause of central vision loss in the elderly. The development of effective treatments has been hindered by the lack of reliable animal models that recapitulate the structural, functional, and molecular hallmarks of GA. In this study, we established and extensively characterized a sodium iodate (NaIO3)-induced model of GA in pigmented Long Evans rats using a comprehensive set of in vivo and histological techniques. NaIO3 was administered intraperitoneally at 80 mg/kg to induce bilateral retinal degeneration. Morphological, functional, and ultrastructural changes were evaluated using scanning laser ophthalmoscopy (SLO), optical coherence tomography (OCT), electroretinography (ERG), light and electron microscopy, and immunohistochemistry at pre-dose and 3, 7, and 14 days post-injection. The model exhibited typical GA features including choriocapillaris loss, RPE degeneration, photoreceptor death, Bruch's membrane remodeling, and mitochondrial damage. Complement activation (C3, C5b-9) and immune cell infiltration (Iba1, CD68) were observed, along with gliosis and RPE65 loss. ERG analysis revealed profound and persistent functional deficits. These findings demonstrate that the NaIO3 rat model robustly mimics the key pathological events in GA, particularly at 7 days post-injection, making it a suitable model for preclinical evaluation of therapeutic interventions targeting choriocapillaris and RPE protection.},
}

Animals
*Geographic Atrophy/chemically induced/pathology/metabolism
*Iodates/toxicity
Rats
Disease Models, Animal
Rats, Long-Evans
Retinal Pigment Epithelium/pathology/metabolism
*Inflammation/pathology/metabolism/chemically induced
Tomography, Optical Coherence
Electroretinography
Male

@article {pmid41341962,
year = {2025},
author = {Ly, A and Harnick, E and Jowsey, T and Bannatyne, AJ},
title = {Qualitative Factors Impacting Patients and Clinicians Regarding Intravitreal Injections for Retinal Disorders: A Scoping Review.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {4349-4365},
pmid = {41341962},
issn = {1177-5467},
abstract = {BACKGROUND: Intravitreal injections are among the most frequently performed eye procedures worldwide. They are vital in managing vision-related retinal conditions such as neovascular age-related macular degeneration, diabetic macular edema and retinal vein occlusion. This review scopes qualitative research concerning people's beliefs, perspectives, experiences and behaviors towards intravitreal injections.

METHODS: Academic databases (PubMed, Embase, CINAHL and Web of Science) were searched for studies focused on qualitative research of intravitreal injections in adult patients, published between January 2000 and May 2024. We extracted data regarding publication and participants' characteristics, main study objectives, and methodological approaches.

RESULTS: Of the 795 identified citations, 28 met the inclusion criteria. Most studies reported on patients' emotional experiences of undergoing intravitreal injections, with the fear of vision loss compounded with ongoing injections prompting significant anxiety and uncertainty for patients. Other studies also reported on the physical component as the invasiveness of the procedure caused pain and discomfort, which varied with the clinician's delivery of the injection. One study reported on clinician experiences of performing intravitreal injections, stating that the treatment decisions are dependent on patient-related factors such as their adherence to regular injections. Overall, qualitative research in ophthalmology is increasing, with most studies employing semi-structured interviews with thematic analysis.

CONCLUSION: Qualitative research offers valuable insights into both patient and clinician experiences of intravitreal injections, which can shape person-centered and sustainable models of intravitreal treatment. Understanding qualitative factors such as personal experiences and barriers to treatment can refine the delivery of intravitreal injections and ultimately improve patient adherence.},
}

@article {pmid41340913,
year = {2025},
author = {Sun, M and Wang, J and Fan, W and Wang, K and Wang, Y and Zhang, J and Ding, S and Zhang, C and Feng, Z and Wang, YG and Song, Z and Tao, Y},
title = {From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics.},
journal = {Materials today. Bio},
volume = {35},
number = {},
pages = {102537},
pmid = {41340913},
issn = {2590-0064},
abstract = {Delivering medications to targeted lesions poses significant challenges due to the unique anatomical structure and physical barriers of the eyeball. Polymer nanomicelles are spontaneously assembled from surfactants and amphiphilic polymers, encapsulating insoluble drugs within their cores to augment their hydrosolubility. Nanomicelles have demonstrated potential to surmount these biological hurdles and convey encapsulated therapeutic agents to intended sites. Nanomicelle can prolong the drug half-life and promote molecule permeation through ocular epithelium. Notably, they can be formulated at concentrations marginally exceeding the critical micelle concentration while maintaining a stable conformation, thereby boosting therapeutic effectiveness. Moreover, the physicochemical attributes of polymeric micelles can be precisely adjusted by integrating diverse hydrophilic or hydrophobic moieties. Surface modifications can further impart specific charges or facilitate targeted organ delivery enhancing adhesion to ocular tissues and mitigating systemic toxicity. This review delves into the utilization of polymer nanomicelles in ophthalmological practice, encompassing block copolymer design, the pharmacokinetics of encapsulated drugs within nanomicelles, and the molecule pathways governing nanomedicines. This review also explores their applications in treating ocular disorders including infectious keratitis, DED, glaucoma, corneal graft rejection, neovascular age-related macular degeneration (nAMD), and DR, while introducing progress in clinical deployment and potentials in ocular diagnosis. We also discuss the key challenges in clinical translation and scalable manufacturing. With continued optimization, polymer nanomicelles are poised to become a versatile, non-invasive platform for personalized ophthalmologic therapies.},
}

@article {pmid41337039,
year = {2025},
author = {Abay, SG and Asmare, MH and Geurts, L},
title = {An Affordable Smartphone-based Fundus Imaging Device for Retinal Examination.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-6},
doi = {10.1109/EMBC58623.2025.11254224},
pmid = {41337039},
issn = {2694-0604},
mesh = {*Smartphone ; Humans ; *Fundus Oculi ; *Retina/pathology/diagnostic imaging ; Glaucoma/diagnosis ; Equipment Design ; Optic Disk/pathology ; },
abstract = {Fundus imaging is widely used for diagnosing and monitoring ocular diseases such as diabetic retinopathy, glaucoma, and age-related macular degeneration. However, the high cost and limited availability of conventional fundus cameras pose significant barriers, particularly in resource-constrained settings. This study introduces the Glaucoma Screening on Phone (GSoP), an affordable and portable smartphone-based fundus imaging adapter designed to address these challenges. The adapter is developed using accessible and cost-effective components. We recorded retinal videos from dilated pupil with a focus on the optic disc region, which provides critical information on the degeneration of the optic nerve. While field testing revealed artifacts such as glare that reduced overall image quality, the GSoP demonstrated its ability to capture diagnostically relevant images of the optic disc region. A subjective qualitative comparison with the commercially available ophthalmoscope called oDocs-nun showed that although the GSoP's field of view is smaller, it effectively highlights the optic nerve head, a critical area for glaucoma screening. Our approach is well-suited for mydriatic video-based screening due to its limited field of view. With a production cost of under C10, the GSoP offers a practical and accessible solution for primary healthcare and educational purposes. Future improvements, including glare reduction mechanisms, AI-driven automation, and modular design options, have the potential to enhance its diagnostic capabilities and broaden its impact.},
}

*Smartphone
Humans
*Fundus Oculi
*Retina/pathology/diagnostic imaging
Glaucoma/diagnosis
Equipment Design
Optic Disk/pathology

@article {pmid41335743,
year = {2025},
author = {Herrero-Tudela, M and Romero-Oraa, R and Hornero, R and Gutierrez-Tobal, GC and Lopez, MI and Romero-Aroca, P and Garcia, M},
title = {Explainable Artificial Intelligence for Early Detection and Diagnosis of Age-Related Macular Degeneration.},
journal = {Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference},
volume = {2025},
number = {},
pages = {1-4},
doi = {10.1109/EMBC58623.2025.11254905},
pmid = {41335743},
issn = {2694-0604},
mesh = {Humans ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Artificial Intelligence ; Early Diagnosis ; Algorithms ; Neural Networks, Computer ; Deep Learning ; Diagnosis, Computer-Assisted/methods ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of blindness in older adults. Early identification of individuals at risk of progressing from an asymptomatic stage to advanced AMD is critical for preventing severe vision loss. Automated image assessment systems for AMD can enhance screening efficiency by reducing time, cost, and effort. Despite the success of convolutional neural networks in AMD detection, their limited interpretability restricts their use in clinical practice. To address this issue, we present an explainable deep-learning approach based on ResNetRS-200, incorporating Kernel SHAP for model interpretability. Our approach achieved a quadratic kappa of 0.6927 and an accuracy of 60.95% on the publicly available Age-Related Eye Disease Study dataset, while achieving a quadratic kappa of 0.7784 and an accuracy of 77.95% on a private dataset. Kernel SHAP analysis highlighted specific retinal regions close to the macula influencing the predictions of the model, providing a clinically interpretable framework, and enhancing diagnostic confidence. Our findings demonstrate the effectiveness of the proposed framework for automated AMD grading. Therefore, the proposed method could be an explainable diagnostic aid for the early detection and grading of AMD.Clinical relevanceThis research establishes the useful- ness of an eXplainable Artificial Intelligence approach using ResNetRS-200 architecture and Kernel SHAP for automated AMD grading.},
}

Humans
*Macular Degeneration/diagnosis/diagnostic imaging
*Artificial Intelligence
Early Diagnosis
Algorithms
Neural Networks, Computer
Deep Learning
Diagnosis, Computer-Assisted/methods

@article {pmid41335529,
year = {2025},
author = {Machna, B and Jastrzebska-Miazga, I and Pacwa, A and Liu, X and Oseka, M and Smedowski, A},
title = {Experimental models of myopia development: A review of literature.},
journal = {Journal of physiology and pharmacology : an official journal of the Polish Physiological Society},
volume = {76},
number = {4},
pages = {335-367},
doi = {10.26402/jpp.2025.4.01},
pmid = {41335529},
issn = {1899-1505},
mesh = {*Myopia/physiopathology/etiology/epidemiology/pathology ; Humans ; Animals ; *Disease Models, Animal ; Refraction, Ocular ; },
abstract = {Myopia is one of the most prevalent refractive errors and one of the leading causes of visual impairment and blindness worldwide. It results from a mismatch between the axial length and optical power of the eye, resulting in a focal plane that lies in front of the retina. In children and young adults, myopia is most commonly caused by excessive elongation of the eyeball during development - a hallmark of school-age and some early-onset genetic forms of myopia. However, myopic refractive error can also result from other mechanisms, such as increased lens power in age-related nuclear cataracts or corneal steepening in keratoconus, which are not associated with axial elongation. The prevalence of myopia in young Asian adults has increased from 20-30% to 80-85% over the last 50 years. In contrast, recent meta-analytic data for European young adults, emphasizing studies with cycloplegic refraction essential for accuracy, indicate myopia prevalence rates of approximately 19-24%. The prevalence of high myopia (greater than or equal to-6.0 diopters) has increased disproportionately to myopia in the last 50 years, from 1-5% to 10-20% and became a global problem. The reason for this state of affairs is believed to be lifestyle and prolonged near vision activities. Although refractive error can be corrected, sight-threatening pathologies such as retinal detachment, macular degeneration, glaucoma, and cataracts are more challenging to control. Owing to years of research, the biological mechanisms of eye growth and refractive development are increasingly elucidated. The signaling cascade mechanisms that link the retinal image processing and alterations in choroidal thickness and scleral development have also been studied. While the retina can detect defocus and changes in defocus, decades of research have led to a growing understanding of the fundamental pathways in visually guided eye growth, yet the precise initial mechanisms by which the retina senses and transduces these optical signals continue to be an active and important area of investigation. Animal studies have demonstrated that the retina can locally regulate visually guided eye growth through intrinsic mechanisms, even in the absence of direct input from the brain. The precise molecular mechanisms underlying common forms of myopia, particularly those involving axial elongation, are yet to be fully elucidated. This reflects the complexity and multifactorial influences inherent even in these prevalent forms, alongside the challenges posed by experimental models in completely recapitulating all aspects of the human condition.},
}

*Myopia/physiopathology/etiology/epidemiology/pathology
Humans
Animals
*Disease Models, Animal
Refraction, Ocular

@article {pmid41335372,
year = {2025},
author = {Shirley, M},
title = {Elamipretide: First Approval.},
journal = {Drugs},
volume = {},
number = {},
pages = {},
pmid = {41335372},
issn = {1179-1950},
abstract = {Elamipretide (Forzinity™) is a mitochondrial cardiolipin binder being developed by Stealth BioTherapeutics for the treatment of a range of disorders featuring mitochondrial dysfunction. In September 2025, elamipretide was granted accelerated approval in the USA for use to improve muscle strength in adult and pediatric patients with Barth syndrome weighing ≥ 30 kg. With this accelerated approval, elamipretide became the first disease-specific treatment approved for Barth syndrome, an ultra-rare X-linked recessive genetic disorder. Elamipretide is also under phase III clinical development for use in the treatment of dry age-related macular degeneration and mitochondrial myopathies. This article summarizes the milestones in the development of elamipretide leading to this first approval for Barth syndrome.},
}

@article {pmid41335185,
year = {2025},
author = {de Angelis, L and Galasso, M and Di Simplicio, S and Raimondi, R and Vidal-Aroca, F and Romano, MR and Toro, MD and Rizzo, S and Barca, F},
title = {Correction: In Vivo Evaluation of SING IMT™ Alignment for Late-Stage Age-Related Macular Degeneration Using Anterior Segment OCT.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40123-025-01294-w},
pmid = {41335185},
issn = {2193-8245},
}

@article {pmid41335184,
year = {2025},
author = {Augustin, AJ and Koss, M},
title = {Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41335184},
issn = {2193-8245},
}

@article {pmid41335183,
year = {2025},
author = {Borrelli, E and Coco, G and Scorcia, V and Carnevali, A and Reibaldi, M and Giannaccare, G},
title = {A Response to: Letter to the Editor Regarding "Safety, Tolerability, and Short-Term Efficacy of Low-Level Light Therapy for Dry Age-Related Macular Degeneration".},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41335183},
issn = {2193-8245},
}

@article {pmid41334307,
year = {2025},
author = {Sadeghi, E and Mahmoudinezhad, G and Valsecchi, N and Vupparaboina, SC and Bollepalli, SC and Vupparaboina, KK and Sahel, JA and Eller, AW and Chhablani, J},
title = {Long-Term Follow-Up of Dry Age-Related Macular Degeneration Patients.},
journal = {Journal of current ophthalmology},
volume = {37},
number = {1},
pages = {78-85},
pmid = {41334307},
issn = {2452-2325},
abstract = {PURPOSE: To assess the progression rate from dry age-related macular degeneration (dAMD) to advanced AMD and possible risk factors.

METHODS: Demographics, medical and ocular conditions, baseline eye examinations, optical coherence tomography features, and progression rates to advanced AMD were collected.

RESULTS: We included 74 eyes from 47 dAMD patients, with a mean age of 74.58 ± 8.29 years and 38.30% males. During a follow-up period of 8.9 ± 0.4 years, 40 eyes (54.05%) progressed to advanced AMD, with 25 eyes (33.78%) developing neovascular AMD (nAMD) and 22 eyes (29.72%) progressing to geographic atrophy (GA). Patients progressing to advanced AMD were older (77.8 ± 6.5 vs. 73.8 ± 9.5, P = 0.03). A higher incidence of open-angle glaucoma (OAG) was noted in progressing eyes (32.5% vs. 8.8%, P = 0.01), along with thinner baseline central macular thickness (CMT) (247.93 ± 32.55 vs. 268.67 ± 16.75, P = 0.007). Smokers with OAG had a higher tendency to develop nAMD (P < 0.05). Females with lower best-corrected visual acuity (BCVA) were more likely to develop GA (P < 0.001).

CONCLUSIONS: The progression rate to advanced AMD was 54.05% over 8.9 ± 0.4 years. Advanced age, reduced baseline CMT, and lower BCVA were linked to progression. OAG and smoking were associated with higher nAMD, while females had a higher risk of GA.},
}

@article {pmid41334300,
year = {2025},
author = {Sarkar, AD and Kannan, NB and Thakur, S and Balakrishnan, TN and Ramasamy, K},
title = {Long-Term Outcome of Intravitreal Expansile Gas and Bevacizumab Injection for Macular Neovascularization-Induced Subfoveal Hemorrhage: A Retrospective Study.},
journal = {Journal of current ophthalmology},
volume = {37},
number = {1},
pages = {86-92},
pmid = {41334300},
issn = {2452-2325},
abstract = {PURPOSE: To analyze the results of the long-term outcome of pneumatic displacement (PD) with intravitreal bevacizumab (IVB) for subfoveal hemorrhage (SFH) secondary to polypoidal choroidal vasculopathy (PCV)/macular neovascularization secondary to neovascular age-related macular degeneration (n-AMD).

METHODS: This is a retrospective and interventional study executed in the population of southern part of India who attended a tertiary care ophthalmic hospital over a decade. Patients who presented with a complaint of diminution of vision following SFH secondary to PCV or n-AMD who were treated with PD using sulphur hexafluoride (SF6) along with IVB were included in the study. The patients were followed up for at least 24 months posttreatment. Finally, a dataset of 54 patients was chosen who fulfilled all the criteria and a thorough analysis on their long-term outcome was done.

RESULTS: The mean age at baseline was 57.55 ± 13.02 years. Average treatment delay was measured 9.43 ± 5.22 days. Best-corrected visual acuity (BCVA) on presentation was 1.07 ± 0.46 in logMAR. The average size of the SFH was measured 4.46 ± 1.17-disc diameter area. The average long-term follow-up was measured 29.33 ± 4.53 months. Final BCVA improved to 0.74 ± 0.62 in logMAR (P < 0.001). Overall improvement in BCVA was significantly better, although only a minority of patients (n = 24, 44.44%) improved BCVA ≥ 0.3 in logMAR. Subgroup analysis reveals smaller SFH (≤2 disc diameter) and presentation earlier than 1 week shows comparatively better visual outcome.

CONCLUSIONS: The study shows encouraging results on the long-term follow-up with respect to anatomical and visual acuity outcome. This serves as the second largest dataset on PD with IVB for SFH secondary to PCV/n-AMD in ophthalmic literature.},
}

@article {pmid41332270,
year = {2025},
author = {Li, KV and Pan, A and Liu, YV and Antonio-Aguirre, B and Wang, J and Adams, M and McNerney, C and Tun, SBB and Jimenez, K and Lu, Y and Li, Z and McNally, M and Barathi, VA and Johnston, RJ and Singh, MS},
title = {Application of Machine Learning to Discriminate Photoreceptor Cell Species in Xenotransplanted Chimeric Retinas.},
journal = {Clinical and translational science},
volume = {18},
number = {12},
pages = {e70420},
doi = {10.1111/cts.70420},
pmid = {41332270},
issn = {1752-8062},
support = {R01EY033103/EY/NEI NIH HHS/United States ; R01EY030872/EY/NEI NIH HHS/United States ; F31EY033187/EY/NEI NIH HHS/United States ; /FFB/Foundation Fighting Blindness/United States ; //Shulsky Foundation/ ; //Joseph Albert Hekimian Fund/ ; G2019300//BrightFocus Foundation/ ; //Maryland Technology Development Corporation/ ; //Juliette RP Vision Foundation/ ; 147042//Knights Templar Eye Foundation/ ; //Wilmer Pooled Professor Fund (PPF) Lutty Grant/ ; EY001765//Johns Hopkins University/ ; },
mesh = {*Machine Learning ; Animals ; Humans ; Mice ; Swine ; *Transplantation, Heterologous/methods ; *Retina/cytology/transplantation ; *Retinal Degeneration/pathology/therapy ; *Photoreceptor Cells, Vertebrate/transplantation ; Disease Models, Animal ; Species Specificity ; Organoids/transplantation/cytology ; Heterografts ; Human Embryonic Stem Cells/transplantation/cytology ; },
abstract = {Photoreceptor transplantation is being studied to restore visual function in retinal diseases causing blindness, including age-related macular degeneration, hereditary eye diseases, and traumatic retinopathy. Preclinical studies often involve delivering exogenous human photoreceptor cells into animal models' retinas. A key readout in such experiments is distinguishing donor cell integration from artificial labeling secondary to material transfer of cytosolic or nuclear labels. Recognizing donor (human) versus animal photoreceptor nuclei is key, but purely immunohistology discrimination is challenging due to antigenic species overlap or intercellular antigen transfer. To address this, we sought to develop and validate a computational technique to discriminate between photoreceptor cells of different animal species based on machine learning of nuclear morphology. We aim to evaluate the feasibility of computer-assisted nuclear detection combined with random forest classification to automate species differentiation in DAPI-stained photoreceptors after xenotransplantation into mouse and pig retinas. Our models were trained on single-species samples and validated with mixed-species samples. We then transplanted human embryonic stem cell-derived retinal organoid cells into rodent and pig retinal degeneration models. The random forest model accurately determined cell identity post-xenotransplantation, validated by histological assessment using an antihuman nuclear antibody. Our results support the potential efficacy of employing machine learning image analysis and classification techniques that may promote experimental rigor, minimize observer bias, and enable high throughput semiautomated workflows for transplantation outcomes analysis. The methodological framework reported here may enable a more nuanced and precise analysis of the behavior of transplanted photoreceptors for the purposes of human retinal regeneration.},
}

*Machine Learning
Animals
Humans
Mice
Swine
*Transplantation, Heterologous/methods
*Retina/cytology/transplantation
*Retinal Degeneration/pathology/therapy
*Photoreceptor Cells, Vertebrate/transplantation
Disease Models, Animal
Species Specificity
Organoids/transplantation/cytology
Heterografts
Human Embryonic Stem Cells/transplantation/cytology

@article {pmid41331277,
year = {2025},
author = {Moon, S and Park, S and Kim, CG and Kim, J and Yoon, YS and Kim, JH},
title = {Predicting visual acuity using optical coherence tomography in patients with neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-28738-4},
pmid = {41331277},
issn = {2045-2322},
support = {25ZK1100//Electronics and Telecommunications Research Institute/ ; },
abstract = {This study aimed to assess the feasibility of an artificial intelligence(AI) model to predict visual acuity(VA) using optical coherence tomography(OCT) in treatment-naïve patients with neovascular age-related macular degeneration (AMD). This retrospective study enrolled 240 patients(240 eyes) with pseudophakic neovascular AMD who received antivascular endothelial growth factor therapy. Each patient underwent 10 visits where they underwent best-corrected visual acuity(BCVA) testing and horizontal OCT scans, yielding 2,400 images. The images were cropped, resized to 224 × 224 pixels, and partitioned at the patient level to avoid data leakage. A pretrained VGG16 CNN was modified for five-class VA classification (< 0.1, 0.1-0.3, 0.3-0.5, 0.5-0.8, ≥ 0.8). The performance was assessed by five-fold cross-validation using the macro-averaged AUC, accuracy, Top-2 accuracy, and binary accuracy (threshold VA = 0.5). The average performance showed a macro-averaged AUC of 0.772, accuracy of 50.3%, Top-2 accuracy of 71.0%, and binary accuracy of 79.6%. For high-confidence predictions (29.2% of the samples), the accuracy improved to 74.1%, with a binary accuracy of 94.2%. ROC analyses demonstrated AUCs of 0.73-0.83 across VA categories, with the strongest discrimination for VA < 0.1 (AUC 0.83). The confusion matrix showed that the VA 0.5-0.8 and ≥ 0.8 categories achieved relatively higher accuracies; however, misclassifications mainly occurred between these adjacent ranges, with frequent bidirectional errors observed. Our pretrained VGG16 showed moderate ability at predicting VA from OCT images in patients with neovascular AMD. While the overall classification was limited, high binary accuracy highlights the potential clinical value of distinguishing good from poor vision.},
}

@article {pmid41329005,
year = {2025},
author = {Trinh, M and Duong, A and Cheung, R and Chen, S and Ng, D and Friedrich, J and Hodge, C and Nivison-Smith, L and Ly, A},
title = {Determinants of Intergrader Agreement for Key Retinal Photography and OCT Biomarkers in AMD.},
journal = {Translational vision science & technology},
volume = {14},
number = {12},
pages = {4},
doi = {10.1167/tvst.14.12.4},
pmid = {41329005},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Male ; Female ; Aged ; Biomarkers ; *Macular Degeneration/diagnosis/diagnostic imaging ; *Photography/methods ; Middle Aged ; Aged, 80 and over ; Retinal Drusen ; *Retina/pathology/diagnostic imaging ; Retinal Pigment Epithelium/pathology ; },
abstract = {PURPOSE: To quantify determinants of intergrader agreement for key retinal photography and optical coherence tomography (OCT) biomarkers in early to intermediate age-related macular degeneration (AMD) and to inform future consensus definitions and grading protocol.

METHODS: Single eyes from 269 participants with early to intermediate AMD were consecutively sampled. Retinal photographs were evaluated for the presence of large drusen and pigmentary abnormalities. OCT B-scans were graded for reticular pseudodrusen (RPD), outer retinal band abnormality (external limiting membrane [ELM], ellipsoid zone [EZ], and retinal pigment epithelium [RPE]), nascent geographic atrophy (nGA), intraretinal hyperreflective foci (IHRFs), hyporeflective drusen cores (hDCs), shallow irregular RPE elevations (SIREs), and drusenoid pigment epithelial detachment (DPED). Biomarkers were classified using a trinary certainty system: "definitely present" (≥90%), "questionably present" (50%-90%), or "absent" (<50%). The main outcome was odds of intergrader agreement from generalized estimating equations adjusting for intraparticipant correlations, biomarker type, and eye- and participant-level factors.

RESULTS: Odds of agreement were comparable for large drusen, nGA, RPE abnormality, IHRF, and ELM abnormality; higher for RPD (odds ratio [95% confidence interval], 3.17 [1.56-6.45], P < 0.01); and lower for SIRE, EZ abnormality, pigmentary abnormalities, hDC, and DPED (up to 0.5 [0.32-0.78], P < 0.01). Agreement improved with higher grading certainty (1.4 [1.22-1.6], P < 0.0001) but declined with age (per decade, 0.8 [0.7-0.93], P < 0.01).

CONCLUSIONS: Biomarker type, grading certainty, and participant age influence OCT agreement. Consensus definitions and grading protocols, including the use of high certainty thresholds (≥90%), may improve consistency.

TRANSLATIONAL RELEVANCE: Implementing consensus definitions and protocols can improve agreement and strengthen the clinical utility of OCT biomarkers in AMD.},
}

Humans
*Tomography, Optical Coherence/methods
Male
Female
Aged
Biomarkers
*Macular Degeneration/diagnosis/diagnostic imaging
*Photography/methods
Middle Aged
Aged, 80 and over
Retinal Drusen
*Retina/pathology/diagnostic imaging
Retinal Pigment Epithelium/pathology

@article {pmid41328785,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Wang, YX and Jonas, RA},
title = {Associations of macular drusen in an East Asian population. The Beijing Eye Study.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70043},
pmid = {41328785},
issn = {1755-3768},
support = {82271086//National Natural Science Foundation of China/ ; },
abstract = {PURPOSE: To assess associations of macular drusen in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease.

METHODS: Participants of the population-based cross-sectional Beijing Eye Study underwent optical coherence tomography. Macular volume scans were assessed for macular drusen.

RESULTS: The study included 870 eyes (870 participants) (age: 64.7 ± 9.9 years; range: 50-91 years), randomly selected within the groups of early AMD (n = 356 (40.9%) eyes), intermediate AMD (n = 201; 23.1%), late AMD (n = 6; 0.7%) and within eyes without AMD (n = 307; 35.3%). In multivariable analysis, higher drusen count was associated (r[2] = 25) with older age (beta: 0.08; p = 0.048), higher serum concentration of cholesterol (beta: 0.10; p = 0.008), shorter axial length (beta: -0.09; p = 0.03), thicker subfoveal choroidal thickness (beta: 0.08; p = 0.04), higher prevalences of macular hyperpigmentations (beta: 0.13; p < 0.001), hyperreflective foci (HRFs) (beta: 0.12; p = 0.004) and reticular pseudodrusen (beta: 0.27; p < 0.001), and a lower prevalence of a visible Henle's layer (beta: -0.15; p < 0.001). Larger drusen size was associated with shorter axial length (beta: -0.08; p = 0.03), thicker subfoveal choroidal thickness (beta: 0.18; p < 0.001), higher prevalences of macular hypopigmentations (beta: 0.14; p < 0.001) and HRFs (beta: 0.31; p < 0.001), and lower prevalences of a visible Henle's layer (beta: -0.19; p < 0.001) and of reticular pseudodrusen (beta: -0.09; p = 0.02).

CONCLUSIONS: In this population-based study on Chinese, higher macular drusen count was associated with shorter axial length, thicker subfoveal choroidal thickness, higher prevalences of macular hyperpigmentations, HRFs and reticular pseudodrusen and lower prevalence of a visible Henle's layer. These findings may be clinically helpful and etiologically interesting.},
}

@article {pmid41328469,
year = {2025},
author = {Ermilov, VV and Nesterova, AA},
title = {[Amyloidogenesis and neurotrophic dysfunction in age-related macular degeneration in correlation with Alzheimer's disease].},
journal = {Arkhiv patologii},
volume = {87},
number = {6},
pages = {61-68},
doi = {10.17116/patol20258706161},
pmid = {41328469},
issn = {0004-1955},
mesh = {Humans ; *Alzheimer Disease/pathology/metabolism/genetics/complications ; *Macular Degeneration/pathology/metabolism/genetics/complications ; *Amyloidosis/pathology/metabolism/genetics ; *Amyloid/metabolism/genetics ; Aged ; Glaucoma, Open-Angle/pathology/metabolism/genetics ; },
abstract = {The pathogenesis of diseases associated with amyloid deposition in various organs and tissues has been a concern for researchers and clinicians since their discovery. Particular attention is paid to the relationship between amyloidogenesis and neurotrophic disorders in age-related neurodegenerative pathology. In this context, the amyloid cascade theory and the neurotrophic dysfunction theory remain relevant, as evidenced by the results of numerous studies conducted in recent years. Meanwhile, it has been shown that amyloidosis, being a systemic pathological process, affects ocular tissues and extraocular structures in various forms with diverse clinical and morphological manifestations. This highlights the need for improved diagnostics of ocular amyloidosis and the study of its association with geriatric ophthalmic diseases such as age-related macular degeneration (AMD), senile cataract, primary open-angle glaucoma, and pseudoexfoliation syndrome. Accumulating evidence suggests that both amyloidogenesis and neurotrophic disturbances share common triggers and mutually contribute to the development of neurodegenerative pathology in both AMD and Alzheimer's disease (AD). Therapeutic strategies aimed not only at suppressing amyloidogenesis and correcting neurotrophic dysfunction but also at the overall regulation of these two pathogenic mechanisms may have a positive effect on geriatric ophthalmic diseases and AD, significantly improving the quality of life of elderly patients. This article summarizes current concepts on the role of neurotrophic dysfunction and amyloidogenic processes in the development of AMD.},
}

Humans
*Alzheimer Disease/pathology/metabolism/genetics/complications
*Macular Degeneration/pathology/metabolism/genetics/complications
*Amyloidosis/pathology/metabolism/genetics
*Amyloid/metabolism/genetics
Aged
Glaucoma, Open-Angle/pathology/metabolism/genetics

@article {pmid41327637,
year = {2025},
author = {Jian, L and Huang, Z and Qi, J and Meng, J and Zhang, K and Zhu, X},
title = {Associations between estimated glucose disposal rate and age-related ocular diseases in cardiovascular-kidney-metabolic syndrome stages 0-3: a large prospective cohort study.},
journal = {BMJ open ophthalmology},
volume = {10},
number = {1},
pages = {},
pmid = {41327637},
issn = {2397-3269},
mesh = {Humans ; Prospective Studies ; Female ; Male ; *Metabolic Syndrome/complications/metabolism ; Middle Aged ; *Eye Diseases/epidemiology/etiology/metabolism ; Aged ; Risk Factors ; *Blood Glucose/metabolism ; *Cardiovascular Diseases/complications/metabolism ; Incidence ; United Kingdom/epidemiology ; Follow-Up Studies ; },
abstract = {OBJECTIVE: This study investigated the relationship between estimated glucose disposal rate (eGDR) and the risk of age-related ocular diseases, including macular degeneration, glaucoma, cataracts, diabetic retinopathy (DR) and retinal detachment (RD), in individuals with stages 0-3 of cardiovascular-kidney-metabolic (CKM) syndrome.

METHODS AND ANALYSIS: This prospective cohort study included 223 120 participants from the UK Biobank. The CKM stages were defined based on adiposity, metabolic risk factors and subclinical cardiovascular disease. Lower eGDR values indicate greater insulin resistance. Outcomes were incidences of macular degeneration, glaucoma, cataract, DR and RD. HRs and 95% CIs were estimated using Cox proportional hazards models. Non-linear relationships were explored using restricted cubic splines.

RESULTS: The study showed that macular degeneration (HR 0.92, 95% CI 0.87 to 0.97, p=0.001) and glaucoma (HR 0.91, 95% CI 0.87 to 0.95, p<0.001) were linearly associated with eGDR. Cataracts exhibited a U-shaped association with eGDR (P non-linear=0.001) and DR exhibited an L-shaped association (P non-linear=0.018). Quartile stratification of eGDR significantly differentiated risk in DR (Q4 vs Q1: HR 0.15, 95% CI 0.04 to 0.52, p=0.003) and RD (Q4 vs Q1: HR 0.65, 95% CI 0.47 to 0.89, p=0.007). Stratified effects analysis revealed that these associations were more significant in advanced CKM syndrome stages.

CONCLUSIONS: eGDR is associated with ocular diseases risk in CKM syndrome, especially in advanced stages. This finding suggests the potential use of eGDR for guiding ophthalmic screening in CKM management.},
}

Humans
Prospective Studies
Female
Male
*Metabolic Syndrome/complications/metabolism
Middle Aged
*Eye Diseases/epidemiology/etiology/metabolism
Aged
Risk Factors
*Blood Glucose/metabolism
*Cardiovascular Diseases/complications/metabolism
Incidence
United Kingdom/epidemiology
Follow-Up Studies

@article {pmid41326361,
year = {2025},
author = {Sarkar, S and Kannan, R and Panigrahi, T and Veeramani, K and Mb, T and Shanker Bhattacharya, S and Ghosh, A},
title = {Comparative transcriptomic analysis of retinal response to diverse cellular stresses reveals relative contributions of different cell death processes and signalling networks.},
journal = {Cell death & disease},
volume = {16},
number = {1},
pages = {876},
pmid = {41326361},
issn = {2041-4889},
support = {IA/TSG/20/1/600029//DBT India Alliance (Wellcome Trust/DBT India Alliance)/ ; },
mesh = {Animals ; Oxidative Stress/genetics ; *Gene Expression Profiling ; Mice ; Mice, Inbred C57BL ; Cell Death/genetics ; *Signal Transduction/genetics ; Endoplasmic Reticulum Stress/genetics ; *Retina/metabolism/pathology ; *Transcriptome ; Retinal Pigment Epithelium/metabolism/pathology ; Apoptosis/genetics ; *Retinal Degeneration/genetics/pathology/metabolism ; },
abstract = {Retinal degeneration comprises a diverse group of progressive disorders leading to visual impairment and ultimately blindness. These include inherited retinal dystrophies (IRDs), diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma, affecting millions worldwide. The underlying pathology involves dysfunction and death of photoreceptor cells and the retinal pigment epithelium (RPE), driven by various stress-induced cell death mechanisms. Although multiple pathways have been reported, the relative contribution of each remains incompletely understood, highlighting the need for further investigation. Therefore, we studied how different stress types that induce retinal degeneration alter the global gene expression profile in vivo (C57BL/6 mice), aiming to identify predominant cell death mechanisms as well as key genes and networks. Retinal toxicity was induced using established models of oxidative stress, hypoxia, endoplasmic reticulum (ER) stress, and chronic inflammation. Transcriptomic profiling revealed both unique and convergent gene expression changes associated with each stressor. In total, 170, 328, 146, and 151 genes were significantly altered under oxidative stress, inflammation, ER stress, and hypoxia, respectively (Log2 fold change >2 or <-2; p < 0.05). Genes such as Arhgap26, Ccdc9, Ube2e2, and Fndc3b were commonly dysregulated across ER stress, inflammation, and oxidative stress, whereas Nfix, Elp6, Naca, and Plcd3 were selectively altered in oxidative stress, inflammation, ER stress, and hypoxia, respectively. Analysis of cell death-related gene subsets revealed that pyroptosis was commonly activated across different stress types. Additionally, autophagy-mediated cell death, ferroptosis, and extrinsic apoptosis were preferentially associated with oxidative stress, chronic inflammation, and hypoxia, respectively. Both ER and oxidative stress models showed strong activation of autophagy-associated cell death. Together, these findings delineate distinct molecular signatures and predominant cell death mechanisms triggered by specific stressors, providing important insights that could aid in developing targeted therapies to prevent or slow retinal degeneration.},
}

Animals
Oxidative Stress/genetics
*Gene Expression Profiling
Mice
Mice, Inbred C57BL
Cell Death/genetics
*Signal Transduction/genetics
Endoplasmic Reticulum Stress/genetics
*Retina/metabolism/pathology
*Transcriptome
Retinal Pigment Epithelium/metabolism/pathology
Apoptosis/genetics
*Retinal Degeneration/genetics/pathology/metabolism

@article {pmid41325920,
year = {2025},
author = {Wang, Z and Zhang, Q and Li, B and Chen, J and Yoshida, S and Sun, B and Zhou, Y},
title = {tRNA-derived small RNAs-Biogenesis, functions, and potential applications in ocular diseases: A review.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {149334},
doi = {10.1016/j.ijbiomac.2025.149334},
pmid = {41325920},
issn = {1879-0003},
abstract = {tRNA-derived small RNAs (tsRNAs), a burgeoning class of small non-coding RNAs, are emerging as pivotal macromolecular regulators in gene expression and cellular signaling networks. Derived from specific cleavage of precursor or mature tRNAs, these molecules exhibit diverse functionalities, including epigenetic remodeling, transcriptional regulation, and translational modulation. Growing evidence underscores their significant roles in the pathogenesis of various ocular diseases, such as age-related macular degeneration, diabetic retinopathy, myopia, and cataract, where they influence critical processes like angiogenesis, inflammation, and neuronal homeostasis. Their dynamic expression profiles in ocular tissues and biofluids position tsRNAs as promising diagnostic biomarkers and therapeutic targets. This review systematically delineates the biogenesis and classification of tsRNAs, elaborates their multifaceted molecular mechanisms, and comprehensively examines their implications in ocular diseases. We further discuss the translational potential of tsRNAs in early detection and precision treatment of ocular diseases, while highlighting current challenges and future directions in this rapidly evolving field.},
}

@article {pmid41324896,
year = {2025},
author = {Kojima, H and Yamashita, A and Nakano, Y and Booka, A and Tatara, Y and Yamada, T and Akimitsu, J and Miyoshi, Y and Osaka, R and Suzuma, K},
title = {Significant Correlation Between Choroidal Thickness and Decrease in Choroidal Blood Flow After Switching to Brolucizumab for Refractory Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41324896},
issn = {2193-8245},
abstract = {INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) therapy suppresses neovascularization in neovascular age-related macular degeneration (nAMD) but may reduce ocular blood flow. However, its relationship with choroidal thickness remains unclear. This study evaluated 1-month outcomes after switching from intravitreal aflibercept or ranibizumab to intravitreal brolucizumab (IVBr) in patients with refractory nAMD.

METHODS: This prospective, single-center study included 50 eyes of 50 patients with nAMD. Changes in best-corrected visual acuity (BCVA), central retinal thickness (CRT), subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), choroidal stromal area (SA), choroidal luminal area (LA), optic nerve head (ONH) mean blur rate (MBR), and choroidal (CHOR) MBR were evaluated before and 1 month after switching to IVBr, with blood flow measured using laser speckle flowgraphy. Univariate analyses were performed to identify potential predictors of changes in CHOR-MBR, and variables with P < 0.1 were entered into a multiple regression model.

RESULTS: BCVA was maintained. CRT decreased from 371.6 ± 118.7 to 288.8 ± 89.7 µm (P < 0.001). SFCT decreased from 231.9 ± 118.7 to 196.0 ± 117.4 µm (P < 0.001). CVI showed no significant changes, while SA and LA exhibited significant reductions. ONH-MBR and CHOR-MBR decreased (P = 0.004 and P < 0.001, respectively). The baseline SFCT was the only significant predictor of change in CHOR-MBR. Older age correlated with thinner baseline SFCT and a greater decrease in CHOR-MBR.

CONCLUSIONS: IVBr is associated with significant reductions in CRT and SFCT and may decrease choroidal blood flow, particularly in older patients and those with thinner SFCTs.

TRIAL REGISTRATION: UMIN-CTR Registration ID, UMIN000041382.},
}

@article {pmid41323371,
year = {2025},
author = {Iwama, Y and Masuda, T and Maeyama, A and Eade, KT and Friedlander, M and Nishida, K and Mandai, M},
title = {Cell-based regenerative therapy for retinal diseases: challenges and emerging bioengineering strategies.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {1101-1112},
pmid = {41323371},
issn = {2352-3204},
abstract = {Cell-based regenerative therapy holds promise for a broad spectrum of retinal diseases characterized by irreversible photoreceptor cell (PRC) loss, including retinitis pigmentosa (RP) and age-related macular degeneration. While gene therapy has delivered landmark successes for selected indications, it does not directly replace lost PRCs and is not well suited for advanced-stages of diseases. In this context, cell-based regenerative approaches-either PRC suspensions or retinal sheets-aim to rebuild the outer retinal circuitry and restore light responses across different retinal diseases. In addition to its relatively high prevalence (1 in 3000-5000 individuals), the PRC-specific degeneration pattern in RP has motivated numerous preclinical studies aimed at clinical application. In this review, we first outline the two major graft modalities-cell suspensions and retinal sheet transplantation-from the perspective of their respective advantages and limitations. Here, we summarize preclinical and clinical evidence for both modalities, highlighting the first-in-human trial of transplantation of human iPSC-derived retinal organoid sheets in late-stage RP, which demonstrated a favorable safety profile and two-year graft survival. We then analyze the challenges that emerged from this first-in-human trial and discuss potential bioengineering and biological solutions. Finally, we consider the prospects of extending these transplantation strategies beyond RP to macular diseases, where PRC replacement may also provide therapeutic benefit. Collectively, the field is transitioning from proof-of-concept to diversified clinical exploration; converging advances in developmental biology, genome engineering, and high-throughput cell analytics are poised to accelerate functional vision restoration in retinal diseases.},
}

@article {pmid41321555,
year = {2025},
author = {Gregori, G and Mangoni, L and Muzi, A and Mariotti, C and Lupidi, M},
title = {Neovascular Maculopathy after Laser Retinal Rejuvenation Therapy in a Young Myopic Patient: A Case Report.},
journal = {Case reports in ophthalmology},
volume = {16},
number = {1},
pages = {841-846},
pmid = {41321555},
issn = {1663-2699},
abstract = {INTRODUCTION: Laser photobiomodulation, including retinal rejuvenation therapy (2RT), is a system which selectively targets the retinal pigment epithelium by a concise 3 ns pulse duration. The advantage of this laser system over the traditional thermal laser is that the pulsed, very short duration laser effects can be titrated as spatially confined photodisruptors without resultant conductive thermal spread and therefore collateral damage. It has been investigated primarily in age-related macular degeneration (AMD), particularly in decreasing drusen and slowing the rate of AMD progression. In this case, we have described a case of neovascular maculopathy occurring shortly after 2RT in a young myopic patient.

CASE PRESENTATION: We report the case of a 28-year-old male who presented with unilateral visual impairment following laser 2RT. Two months before, he was subjected to photorefractive keratectomy for moderate myopia (-3.00 D). The baseline optical coherence tomography (OCT) imaging revealed "sharp-peaked" pigment epithelium detachment (PED) in the subfoveal area. Fluorescein angiography indicated a focal area of irregular foveal hyperfluorescence. Observation was advised, and laser 2RT was performed. However, 1 month later, the patient developed a neovascular lesion in the same eye, confirmed by OCT-angiography, requiring urgent intravitreal anti-VEGF therapy.

CONCLUSIONS: In summary, this case illustrates a progressive maculopathy culminating in choroidal neovascularization triggered by laser 2RT in a young myopic patient.},
}

@article {pmid41318054,
year = {2025},
author = {Zhang, Z and Shan, X and Liang, F and Fang, L},
title = {Integrative single-cell transcriptomic and experimental analyses unveil Qihuang granule's protection against retinal photodamage via PI3K/AKT/mTOR-mediated autophagy.},
journal = {The international journal of biochemistry & cell biology},
volume = {190},
number = {},
pages = {106881},
doi = {10.1016/j.biocel.2025.106881},
pmid = {41318054},
issn = {1878-5875},
abstract = {Light-induced retinal damage is a significant contributor to age-related macular degeneration (AMD). Qihuang granule (QHG), a traditional Chinese herbal formulation, has been clinically employed in the treatment of retinal diseases, including AMD; however, the precise protective mechanisms remain unclear. This study investigated the protective effects and underlying mechanisms of QHG using a rat model of blue light-induced retinal injury and a human retinal pigment epithelial (ARPE-19) cell model. The results demonstrated that QHG significantly alleviated retinal morphological abnormalities, ultrastructural damage, and apoptosis induced by light exposure. Single-cell RNA sequencing further revealed that specific cell clusters were notably enriched in the PI3K-AKT-mTOR and autophagy-related signaling pathways after QHG treatment, characterized by increased MAP1LC3B (LC3B) expression and decreased SQSTM1 (P62) expression. Validation at the protein and gene levels in vivo confirmed that QHG activated the autophagy pathway by downregulating PI3K, AKT, mTOR, and P62 expression while upregulating LC3B expression. Collectively, this study demonstrates that QHG protects against retinal photodamage by modulating autophagy via the PI3K/AKT/mTOR signaling pathway, providing theoretical support for its clinical application in the treatment of AMD.},
}

@article {pmid41317829,
year = {2025},
author = {Kerwin, AF and Perlman, EM and Browning, DJ},
title = {Atrophy Advisor: A Clinical Tool for Dry Macular Degeneration with Geographic Atrophy.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.11.037},
pmid = {41317829},
issn = {1879-1891},
abstract = {OBJECTIVE: To develop and evaluate Atrophy Advisor, a clinical decision tool integrating geographic atrophy (GA) progression and personalized lifespan estimates to help clinicians considering complement factor inhibitor injections for dry macular degeneration with GA.

DESIGN: Retrospective cohort study.

SUBJECTS: Fifty consecutive patients with GA secondary to nonexudative age-related macular degeneration, seen at Wake Forest-affiliated retina clinics from May 2013 to June 2025.

METHODS: Fundus images at two or more timepoints were analyzed using ImageJ to measure the distance from the fovea to the nearest GA edge. Pixel-to-micron conversion was made using an assumed vertical disk diameter of 1800 microns. Demographics, comorbidities, and corrected visual acuities were extracted from records. Lifespan estimates were calculated using University of Connecticut (UCONN) and Social Security Administration (SSA) algorithms and compared to observed outcomes.

MAIN OUTCOME MEASURES: GA edge-to-fovea distance, GA progression rate, corrected visual acuity, and predicted versus observed lifespan.

RESULTS: Median age was 78 years (IQR: 73.8-82.3); 64% were female. Baseline median GA-to-fovea distance was 792 µm (IQR: 509-1213 µm), declining to 395 µm (IQR: 194-702 µm) at last follow-up. Median GA progression was 122 µm/year (range 2-627 µm/year), with a direct relationship between initial distance and progression rate (p=0.006, R²=0.146). Lifespan calculators (UCONN and Atrophy Advisor) yielded median estimates of 11.9 and 11 years, respectively, influencing treatment guidance in 4% of cases.

CONCLUSIONS: Atrophy Advisor is feasible for combining GA progression kinetics and lifespan estimates to inform treatment decisions. Variability in progression rates and lifespan predictions highlights the need for personalized approaches. Limitations include measurement variability and retrospective design; future studies should validate the tool in larger, prospective cohorts.},
}

@article {pmid41317302,
year = {2025},
author = {Hashimoto, Y and Arai, Y and Takahashi, H and Tampo, H and Kondo, R and Takahashi, H and Yoshida, H and Takahashi, R and Inoda, S and Kaburaki, T and Yanagi, Y},
title = {Increased aqueous flare after intravitreal brolucizumab injections compared to aflibercept in 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 = {41317302},
issn = {1435-702X},
support = {21K09751//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: To evaluate aqueous flare values in patients with neovascular age-related macular degeneration (nAMD) receiving anti-vascular endothelial growth factor (VEGF) therapy, including brolucizumab.

METHODS: This retrospective study included 101 patients treated with intravitreal anti-VEGF injections at Jichi Medical University Hospital from March to July 2021. Aqueous flare values were measured in both affected and fellow eyes. The number of treated eyes was 28 for aflibercept and 73 for brolucizumab. Flare values were compared between affected and fellow eyes, and associations with age, gender, drug type, number of injections, disease duration, and time since last injection were analyzed. We also measured flare values from pre-filled syringes.

RESULTS: In unilateral treatment cases, brolucizumab-treated eyes had significantly higher aqueous flare values than fellow eyes (6.7 vs. 6.2 photon counts/ms, P = 0.0032), while no significant difference was observed with aflibercept (6.9 vs. 6.7 pc/ms, P = 0.55). Flare values increased significantly with age in the brolucizumab group (P = 0.0076) but not in the aflibercept group (P = 0.56). The number of brolucizumab injections did not alter flare values. Multivariate analysis identified age as the only significant factor associated with increased aqueous flare. The mean (standard deviation) flare values measured from pre-filled syringes were 430 (15.6) pc/ms for Beovu[®] (brolucizumab) and 161.8 (31) pc/ms for Eylea[®] (aflibercept).

CONCLUSION: In nAMD, aqueous flare values were higher in brolucizumab-treated eyes and increased with age but were unaffected by the number of injections. Different flare values of each drug might affect the aqueous flare values within hours after injection.},
}

@article {pmid41316464,
year = {2025},
author = {Zhang, Z and Yang, H and Tan, L and Li, Y and Ren, X and Li, X},
title = {Associations between the monocyte‑lymphocyte ratio and age‑related macular degeneration among US adults: evidence from NHANES 2005-2008.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00766-2},
pmid = {41316464},
issn = {2056-9920},
support = {TJYXZDXK-037A//Tianjin Key Medical Discipline (Specialty) Construction Project/ ; },
abstract = {BACKGROUND: Previous studies have established an association between age-related macular degeneration (AMD) and chronic systemic inflammation. However, the relationship between AMD and the monocyte-to-lymphocyte ratio (MLR), a novel inflammatory biomarker, remains unclear. In this study, we aimed to investigate the association between MLR and AMD using data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).

METHODS: Data from three NHANES cycles (2005-2008) were analyzed to preliminarily assess the association between MLR and AMD, excluding participants with incomplete data. We utilized weighted logistic regression models, restricted cubic spline functions (RCS) and constructed receiver operating characteristic (ROC) curves to evaluate the association between MLR and AMD.

RESULTS: A total of 4,894 participants were deemed eligible for our analysis, with 379 individuals diagnosed with AMD. The Monocyte to Lymphocyte Ratio (MLR) was significantly elevated in the AMD group compared to the non-AMD group. After adjusting for potential confounding factors, we found that elevated MLR levels were significantly associated with an increased risk of AMD, with an OR of 2.56, 95% CI: (1.17,5.58), P = 0.022. The restricted cubic spline (RCS) analysis revealed a significant nonlinear relationship between MLR and AMD, with an inflection point at 0.26 (nonlinear P < 0.05). Furthermore, the receiver operating characteristic (ROC) curve analysis demonstrated that MLR exhibited acceptable discrimination for AMD.

CONCLUSIONS: Elevated MLR is associated with an increased risk of AMD, suggesting that MLR may serve as a simple and effective clinical biomarker of AMD.},
}

@article {pmid41316395,
year = {2025},
author = {Dundar, A and Cetik Yildiz, S},
title = {Kynurenine pathway metabolites as potential biomarkers in age-related macular degeneration: an ELISA-based prospective study.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {131},
pmid = {41316395},
issn = {2056-9920},
abstract = {OBJECTIVES: Age-related macular degeneration (AMD), in which oxidative stress, inflammation and metabolic imbalances play a role in its pathogenesis, is one of the leading causes of irreversible vision loss. The kynurenine (KYN) pathway, one of the principal routes of tryptophan (TRP) metabolism, constitutes an important mechanism in retinal neurodegeneration. Based on this information, our study aimed to compare the serum TRP, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HAA) and, quinolinic acid (QA) levels of AMD patients and to investigate the diagnostic values of these biomarkers.

METHODS: Serum samples were collected from AMD patients and control groups. TRP, KYN, KYNA, 3HK, 3HAA, and QA levels were measured using a commercial ELISA method. KYN pathway activity, KYN/TRP and, KYNA/3HK ratios were also assessed. Mann-Whitney U test, ROC analysis, Spearman correlation were applied for statistical comparisons.

RESULTS: According to our results, 3HK was significantly higher in the AMD group, while TRP, KYN, QA, and KYNA/3HK ratio were higher in the control. ROC analysis revealed 3HK to be the strongest discriminatory marker. The KYNA/3HK ratio also provided significant diagnostic value. Correlation analysis revealed strong negative correlations between 3HK and KYN, QA, and especially KYNA/3HK. Conversely, strong positive correlations were found between KYN and KYNA/3HK, and between TRP, KYN, QA, and KYNA.

CONCLUSION: KYN pathway metabolites exhibit significant alterations in patients with AMD. 3HK levels and the reduction of the KYNA/3HK ratio suggest a disruption of the neurotoxic-neuroprotective balance and imply that KYN pathway dysfunction may play a role in the pathogenesis of AMD. Among the biomarkers examined, 3HK displayed the highest diagnostic performance, while the KYNA/3HK ratio emerged as an additional biological indicator. These findings indicate that 3HK and the KYNA/3HK ratio may serve as potential biomarker candidates for the early diagnosis and monitoring of AMD.},
}

@article {pmid41316066,
year = {2025},
author = {Pei, Y and Meng, J and He, W and Zhang, K and Guo, D and Lu, Y and Zhu, X},
title = {Unique liver function in high myopia: associations with myopic macular degeneration.},
journal = {BMC ophthalmology},
volume = {25},
number = {1},
pages = {677},
pmid = {41316066},
issn = {1471-2415},
support = {82301188//National Natural Science Foundation of China/ ; 82122017//National Natural Science Foundation of China/ ; },
mesh = {Humans ; Male ; Cross-Sectional Studies ; Female ; Middle Aged ; *Myopia, Degenerative/physiopathology/blood/complications ; *Macular Degeneration/blood/physiopathology/etiology ; Adult ; Liver Function Tests ; *Liver/physiopathology ; ROC Curve ; gamma-Glutamyltransferase/blood ; Lipids/blood ; },
abstract = {PURPOSE: To investigate liver function and lipid indexes in patients with high myopia and their association with myopic macular degeneration (MMD).

METHODS: This cross-sectional comparative study included 995 emmetropic patients and 805 highly myopic patients. Serum levels of liver function and lipid indexes were measured using a Roche C702 biochemical analyzer. Ultra-widefield fundus photographs of eyes were classified according to the International META-PM Classification: Category 0: No myopic retinal degeneration, Category 1: tessellated fundus, Category 2: diffuse choroidal retinal atrophy, Category 3: patchy choroidal retinal atrophy, Category 4: macular atrophy. A machine learning model based on liver function indexes was employed to predict the presence of MMD in patients with high myopia.

RESULTS: Serum levels of albumin (Alb), alkaline phosphatase (ALP), glutamyl transpeptidase (GGT) and triglyceride (TG) were significantly lower, whereas high-density lipoprotein cholesterol (HDL) and apolipoprotein-A (Apo-A) were higher in patients with high myopia than those in emmetropic patients (all P < 0.05). Significant differences in serum ALT and GGT were found among MMD categories (both P < 0.05). Multivariate logistic regression showed that MMD4 was associated with lower serum GGT than MMD1 (P < 0.05). The decision tree model to predict MMD achieved an area under the curve (AUC) of 0.735 using serum GGT (sensitivity = 53.12%; specificity = 82.09%; P < 0.001). When using multiple liver function indexes, the AUC of the model reached 0.803 (sensitivity = 73.4%; specificity = 76.1%; P < 0.001).

CONCLUSION: We identified close associations between liver function and MMD, suggesting serum GGT serve as a potential diagnostic indicator for MMD among highly myopic patients.},
}

Humans
Male
Cross-Sectional Studies
Female
Middle Aged
*Myopia, Degenerative/physiopathology/blood/complications
*Macular Degeneration/blood/physiopathology/etiology
Adult
Liver Function Tests
*Liver/physiopathology
ROC Curve
gamma-Glutamyltransferase/blood
Lipids/blood

@article {pmid41314477,
year = {2025},
author = {Poirot, M and Buñay, J and Ayadi, S and Silvente-Poirot, S and de Medina, P},
title = {Liver X receptors and the hallmarks of aging: From molecular mechanisms to therapeutic opportunities.},
journal = {Ageing research reviews},
volume = {114},
number = {},
pages = {102967},
doi = {10.1016/j.arr.2025.102967},
pmid = {41314477},
issn = {1872-9649},
abstract = {Aging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy, mitochondrial function, epigenetics, senescence, stem cell dynamics, and intercellular communication. This positions LXRs at the crossroads of multiple hallmarks of aging. This review synthesizes current knowledge on endogenous and synthetic LXR ligands, their transcriptional mechanisms, and their effects on the aforementioned hallmarks and age-related pathophysiology. The clinical development of pan-LXR agonists for atherosclerosis has been hindered by side effects, notably hepatic steatosis. Emerging strategies, including LXRβ-selective ligands, selective LXR modulators (SLiMs), and biased agonists such as dendrogenin A, offer ways to separate the protective vascular, metabolic, and neuroprotective effects from adverse outcomes. Additionally, we explore how LXR signaling intersects with the hallmarks of aging and how it can be leveraged to intervene in atherosclerosis, diabetes, cancer, osteoporosis, age-related macular degeneration, and neurodegenerative diseases. Positioning LXRs within the geroscience framework suggests that LXRs may serve as pharmacological hubs to delay aging and its comorbidities. Future work should prioritize isoform- and tissue-selective approaches, metabolite-inspired ligand design, and integration with the hallmarks of aging to unlock the full therapeutic potential of LXRs.},
}

@article {pmid41313467,
year = {2025},
author = {Cheng, X and Lohmann, T and Johnen, S and Walter, P and Baumgarten, S},
title = {Relationship between monocyte-to-lymphocyte ratio and age-related macular degeneration: Findings from a national cross-sectional study.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251402991},
doi = {10.1177/11206721251402991},
pmid = {41313467},
issn = {1724-6016},
abstract = {BackgroundRecent advances have revealed the important role of the immune system in the progression of age-related macular degeneration (AMD). Monocyte-to-lymphocyte ratio (MLR) is a combined marker reflecting inflammation status. However, research on the correlation between MLR and AMD is limited.MethodsIn this cross-sectional analysis, weighted multivariable logistic regression, multinomial logistic regression, subgroup analysis, smoothed curve fitting and threshold effect analysis were used to investigate the relationship between MLR and AMD based on data from the 2005-2008 National Health and Nutrition Examination Survey (NHANES).ResultsThis study included data of 4,655 participants. The proportions of no AMD, early AMD and late AMD were 92.27%, 6.79% and 0.95%, respectively. After adjusting for covariates, weighted multivariable logistic regression analysis revealed that MLR was positively associated with AMD (OR = 3.22, 95%CI 1.32-7.82). Threshold effect analysis revealed that higher MLR associated with prevalence of AMD after MLR was greater than 0.37 (OR = 8.93, 95%CI 2.53-31.60). The diagnostic performance of MLR > 0.37 for AMD was assessed using ROC curve analysis. In addition, MLR was proven to have a significant positive correlation with early AMD (OR = 1.20, 95%CI 1.19-1.21) and late AMD (OR = 9.21, 95%CI 9.10-9.31) through weighted multinomial logistic regression.ConclusionsOur study demonstrates that an elevated MLR is independently associated with the prevalence of AMD.},
}

@article {pmid41312773,
year = {2025},
author = {Ju, X and Ramke, J and Turnbull, PR},
title = {Emerging research on non-neovascular age-related macular degeneration treatments.},
journal = {Clinical & experimental optometry},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/08164622.2025.2579872},
pmid = {41312773},
issn = {1444-0938},
abstract = {Age-related macular degeneration (AMD) is a common condition that causes vision impairment in the elderly, significantly impacting their physical and psychosocial well-being. Historically, treatment options to slow or prevent atrophic AMD progression have been limited but are recently increasing in number. This scoping review aims to provide an overview of the research (both preclinical and clinical) on non-neovascular AMD (including early, intermediate, and geographic atrophy) treatments published in the past decade. Our study protocol was prospectively registered on the Open Science Framework.Searches were conducted on MEDLINE, Embase, ProQuest, and CINAHL for studies investigating treatments for atrophic AMD (including early, intermediate, and geographic atrophy stages) published between 1 January 2014 and 14 July 2024, the search date. Data screening, full-text review, and extraction were independently performed by two researchers. Study characteristics and outcomes were summarised, and the results were synthesised narratively. The search identified 1,211 studies, of which 132 were included in this review. Studies were most often conducted in the United States (n = 92, 68.7%) or Europe (n = 25, 18.5%) and most frequently investigated antioxidant or anti-inflammatory treatments (n = 30, 22.7%) or complement pathway inhibitors (n = 25, 18.9%) as potential therapies. Over three quarters (n = 101, 76.5%) of the included studies reported positive outcomes. Across the decade, the number of studies published increased at an annual rate of 24.0%.This review highlights the growing body of research on atrophic AMD treatments over the past decade, with antioxidant and anti-inflammatory treatments emerging as prominent, promising avenues. However, more phase III human clinical trials are needed to ensure that future therapies effectively serve the global AMD population.},
}

@article {pmid41312453,
year = {2025},
author = {Wei, L and Yan, W and Zhang, K and Gao, F and Li, Z and Pan, R and Zhang, Z and Wang, X},
title = {Allogeneic whole-eye transplantation: advancements, challenges, and future directions in vision restoration.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1691259},
pmid = {41312453},
issn = {2296-858X},
abstract = {Vision loss remains a significant global health burden, primarily driven by irreversible ocular conditions such as age-related macular degeneration (AMD), glaucoma, severe ocular trauma, and intraocular malignancies. Despite advances in retinal prosthetics and stem cell-based therapies, current treatment options are still limited in their ability to fully restore visual function. Allogeneic whole-eye transplantation (WET) has recently gained attention as a novel and potentially transformative strategy for vision restoration. This review synthesizes recent progress in the field, including advancements in microsurgical techniques, immunosuppressive protocols, and neural integration strategies, drawing on evidence from both preclinical animal models and emerging human studies. Key components, including optic nerve (ON) regeneration, vascular anastomosis, immune tolerance, and donor-recipient matching, are critically examined. Furthermore, we address ongoing barriers, including graft viability, chronic rejection, central visual pathway rewiring, and ethical considerations surrounding the procurement of donor eyes. While substantial milestones have been achieved, particularly in experimental settings, clinical translation remains in its early stages. This review highlights current limitations and proposes future directions for multidisciplinary research aimed at overcoming these challenges and advancing WET toward clinical reality.},
}

@article {pmid41311657,
year = {2025},
author = {Hanson, J and Yamamoto, M and Tsui, E and Tsui, I},
title = {Efficacy of faricimab for recalcitrant multifactorial cystoid macular edema.},
journal = {American journal of ophthalmology case reports},
volume = {40},
number = {},
pages = {102475},
pmid = {41311657},
issn = {2451-9936},
abstract = {PURPOSE: More information is emerging on faricimab-svoa (faricimab) used for etiologies beyond wet age-related macular degeneration (AMD) and diabetic macular edema (DME), including ongoing trials for use in macular edema following retinal vein occlusion (RVO). This manuscript describes a case of recalcitrant postoperative cystoid macular edema (CME), confounded by a history of branch retinal vein occlusion (BRVO), in which faricimab resulted in resolution of CME after incomplete response to topical anti-inflammation drops, intravitreal aflibercept and bevacizumab, a corticosteroid intravitreal implant, grid laser therapy, and suprachoroidal triamcinolone acetonide (SCS-TA).

OBSERVATIONS: An 83-year-old pseudophakic male with history of steroid-induced ocular hypertension and BRVO with mild preoperative CME and visual acuity (VA) of 20/160 presented with significant worsening CME following a pars plana vitrectomy (PPV) and internal limiting membrane (ILM) peel for an epiretinal membrane (ERM) in the right eye. CME persisted for eight years despite treatment with topical anti-inflammatories, anti-VEGF injections, a dexamethasone intravitreal implant, grid laser therapy, and a SCS-TA injection. However, after 3 faricimab injections, CME resolved with a CST change from 748 μm to 339 μm and VA improved from 20/50 to 20/40.

CONCLUSIONS AND IMPORTANCE: This case demonstrates the effectiveness of faricimab in treatment of CME resistant to other therapies and the importance of continued attempts at using new agents for chronic, recurrent CME. The unique benefits of new agents like faricimab, with both VEGF and Ang-2 inhibition, may be particularly helpful in mixed or inflammatory CME when other proven therapies have failed.},
}

@article {pmid41310732,
year = {2025},
author = {Yoo, HS and Chakravarthy, H and Xi, J and Cui, J and Ai, Z and Hosseini, A and Song, J and Tan, N and Ma, N and Zhou, C and Li, B and Bell, R and Haegert, A and Le Bihan, S and Ju, MJ and Granville, DJ and Matsubara, JA},
title = {Granzyme B contributes to subretinal fibrosis in neovascular age-related macular degeneration by modulating inflammation and epithelial-mesenchymal transition.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-025-03619-9},
pmid = {41310732},
issn = {1742-2094},
}

@article {pmid41308944,
year = {2025},
author = {Wang, L and Wang, Z},
title = {Therapeutic targeting of lncRNAs in Age-Related Ocular Disease.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110771},
doi = {10.1016/j.exer.2025.110771},
pmid = {41308944},
issn = {1096-0007},
abstract = {Age-related ocular diseases, including age-related macular degeneration, cataract, and glaucoma, are significant causes of visual loss and blindness worldwide. Long non-coding RNAs (lncRNAs) participate in gene regulation, epigenetic control, and cellular homeostasis, and increasing evidence implicates them in age-related ocular disorders by modulating oxidative stress, inflammation, angiogenesis, apoptosis, and extracellular matrix remodeling within ocular tissues. LncRNAs are linked to retinal degeneration, lens opacity, and optic nerve damage, supporting their promise as biomarkers and targets for treatment approaches. This review summarizes current understanding of lncRNA-related processes in age-related ocular disease and emphasizes their potential roles in diagnosis, prognosis, and treatment. An integrated view of lncRNA function in aging ocular tissues may guide precision medicine strategies to prevent or slow vision loss in older individuals.},
}

@article {pmid41308857,
year = {2025},
author = {Cen, S and Liu, S and Zhao, M and Tang, L},
title = {Comparative efficacy and safety of faricimab, aflibercept, conbercept, and ranibizumab for neovascular age-related macular degeneration: A systematic review and network meta-analysis.},
journal = {European journal of pharmacology},
volume = {1010},
number = {},
pages = {178406},
doi = {10.1016/j.ejphar.2025.178406},
pmid = {41308857},
issn = {1879-0712},
abstract = {BACKGROUND: Existing meta-analyses of anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration focus mainly on ranibizumab and aflibercept, with limited data on newer agents (faricimab, conbercept). This network meta-analysis (NMA) comprehensively compares all four key agents.

METHODS: We systematically searched multiple databases for randomized controlled trials. Bayesian random-effects network meta-analysis was conducted, with evidence certainty assessed using CINeMA (Confidence in Network Meta-Analysis).

RESULTS: Thirty-nine randomized controlled trials involving 11,548 participants were included. For best-corrected visual acuity, agents showed comparable efficacy (high to moderate evidence); differences were neither statistically nor clinically significant. Choroidal neovascularization regression showed no important differences (mostly low certainty evidence). For retinal thickness, superior reductions versus ranibizumab 0.5 mg were observed with aflibercept 2 mg (MD: -14.27, 95 % CrI: -27.25, -1.75; high certainty), aflibercept 8 mg (MD: -32.43, 95 % CrI: -57.40, -7.75; high certainty), and conbercept 0.5 mg (MD: -10.26, 95 % CrI: -19.43, -0.98; moderate certainty). Faricimab required significantly fewer injections (high certainty evidence). Aflibercept 2 mg showed better ocular safety than faricimab 6 mg (OR: 0.58, 95 % CrI: 0.37, 0.90) and ranibizumab 0.5 mg (OR: 0.72, 95 % CrI: 0.53, 0.97; high certainty).

CONCLUSION: Aflibercept and conbercept may be preferred when anatomical outcomes are prioritized, whereas faricimab's extended dosing interval could benefit treatment-adherent populations. The superior safety profile of aflibercept 2 mg warrants consideration in risk averse patients. These differential effects support personalized therapeutic decision-making.},
}

@article {pmid41308856,
year = {2025},
author = {Chuang, CC and Chen, YS and Lu, WY and Su, SC and Liao, TY and Yang, SF and Hsieh, YH},
title = {Protective role of Oxyresveratrol against NaIO3-induced oxidative stress in RPE cells via targeting NRF2-mediated ferroptosis in vitro and in vivo.},
journal = {European journal of pharmacology},
volume = {1010},
number = {},
pages = {178402},
doi = {10.1016/j.ejphar.2025.178402},
pmid = {41308856},
issn = {1879-0712},
abstract = {Age-related macular degeneration (AMD) is a chronic retinal disorder that occurs when oxidative damages are gradually accumulated to the center of retina. Oxyresveratrol (OxyR), a naturally occurring stilbene found in many plants, has been reported to exhibit anti-inflammatory and anti-oxidative activities. To fill this gap, we explored the effect of OxyR on retinal pigment epithelial cells in response to oxidative stress and on a mouse model of AMD and further dissected the molecular mechanism underlying OxyR's actions. In this study, we demonstrated that OxyR efficiently impeded both apoptosis and ferroptosis of a human ARPE-19 cells induced by sodium iodate (NaIO3). Such protective effect of OxyR on NaIO3-induced ARPE-19 cells was accompanied with altered expression levels of NRF2, KEAP1, and several ferroptosis-related proteins. Moreover, OxyR treatment, coupled with silencing of NRF2, ferroptosis inhibitor (ferrostatin-1) or depletion of ROS, enhanced the protection of ARPE-19 cells from NaIO3-induced damages. Consistently, oral gavage of OxyR restored the reduction of retinal thickness and attenuated the upregulation of NRF2 in retinal pigment epithelium layers of NaIO3-treated mice. These results demonstrated that OxyR mitigates NaIO3-induced ARPE19 cell death via targeting NRF2-ferroptosis signaling. Our findings provided potential avenues for the use of OxyR in controlling AMD.},
}

@article {pmid41308839,
year = {2025},
author = {Wang, W and Wazny, VK and Mahadzir, MDA and Maier, AB},
title = {Multivitamin and mineral use: A rapid review of meta-analyses on health outcomes.},
journal = {Ageing research reviews},
volume = {114},
number = {},
pages = {102965},
doi = {10.1016/j.arr.2025.102965},
pmid = {41308839},
issn = {1872-9649},
abstract = {Multivitamin and mineral (MVM) supplements are among the most widely used dietary supplements globally, however, their role in promoting healthspan and longevity remains unclear. This review evaluated comprehensive findings from meta-analyses to clarify their health effects. A rapid review of MEDLINE and EMBASE identified 19 eligible meta-analyses published from 2000 to 2025, encompassing 5535,426 participants, including over 333,943 pregnancies and 904,947 children exposed to maternal MVM supplementation. Randomized controlled trials indicated that MVM use improved global cognition, episodic memory, and immediate recall in older or cognitively intact adults, reduced psychological symptoms in healthy individuals, and lowered systolic blood pressure in at-risk populations. However, no benefits were found for all-cause mortality, COVID-19 outcomes, visual acuity, or multiple cognitive domains, and a higher risk of age-related macular degeneration progression was reported. Observational studies found associations between MVM use and a reduced risk of colorectal cancer, coronary heart disease, cataracts, and fragility hip fractures, but not breast or prostate cancer, stroke, or overall mortality. During pregnancy, MVM supplementation was linked to reduced risks of small-for-gestational-age births and pediatric cancers, but not to preterm birth, stillbirth, or low birth weight. Overall, the findings revealed a lack of consistency in the definition of MVM supplementation, and substantial variability in MVM effectiveness depending on population, age, and health status. These results highlighted the importance of shifting from generalized supplementation approaches to more targeted, personalized nutritional strategies to support healthspan and longevity.},
}

@article {pmid41307906,
year = {2025},
author = {Liem, Y and Vemula, V and Lim, CC and Chong, CCY and Choo, JCJ and Cheng, CY and Sabanayagam, C},
title = {Impact of chronic kidney disease on the incidence of visual impairment and age-related eye diseases in a multi-ethnic Asian population.},
journal = {Journal of global health},
volume = {15},
number = {},
pages = {04316},
pmid = {41307906},
issn = {2047-2986},
mesh = {Humans ; Middle Aged ; Aged ; Male ; Female ; *Renal Insufficiency, Chronic/complications/ethnology/epidemiology ; Singapore/epidemiology ; Incidence ; Adult ; Aged, 80 and over ; *Vision Disorders/epidemiology/ethnology ; *Eye Diseases/epidemiology/ethnology ; *Asian People/statistics & numerical data ; Risk Factors ; Cataract/epidemiology ; },
abstract = {BACKGROUND: The kidney and eye share common metabolic and vascular risk factors, and chronic kidney disease (CKD) has been associated with the prevalence of visual impairment (VI). In this study, we examined the association of CKD with incident VI and major age-related eye diseases, including cataract, age-related macular degeneration (AMD), diabetic retinopathy (DR), and glaucoma, in a multi-ethnic Asian population.

METHODS: We analysed data from 6486 Chinese, Malay, and Indian adults aged 40-80 years who participated in the Singapore Epidemiology of Eye Diseases study at baseline (2004-11) and six-year follow-up visit (2011-17) and were free of VI and the respective eye diseases at baseline. We defined CKD (n = 564; 8.7%) as an estimated glomerular filtration rate (eGFR)<60 ml/min/1.73 m[2], and categorised the severity of CKD into stages G1-G5. Eye examinations included refraction, slit-lamp examinations, and retinal imaging. We defined incident VI as best-corrected visual acuity <20/40 in the better eye. Eye diseases examined included cataract, AMD, retinopathy, including DR in those with diabetes and glaucoma. We examined associations between CKD, VI, and eye diseases using multivariable logistic regression models adjusted for age, gender, ethnicity, diabetes, and hypertension status, presenting the results as odds ratios (ORs) and 95% confidence intervals (CIs).

RESULTS: CKD participants had a higher incidence of any VI (14.3% vs. 3.3%; P < 0.001), any AMD (8.0% vs. 5.4%; P < 0.001), and cataracts (65.1% vs. 40.8%; P < 0.001) than non-CKD participants. VI incidence increased with CKD severity in G1-G2 (3.3%), G3a (13.5%), and G3b-G5 (16.3%) (P < 0.001). In multivariable models, CKD was associated with incident VI (OR = 1.47; 95% CI = 1.03-2.10) and moderate/worse DR (OR = 2.62; 95% CI = 1.35-5.10).

CONCLUSIONS: Our results suggest that the presence of CKD increases the risk and severity of VI and eye diseases in Asian adults. Our findings highlight the importance of regular eye exams for CKD patients to reduce the risk of VI.},
}

Humans
Middle Aged
Aged
Male
Female
*Renal Insufficiency, Chronic/complications/ethnology/epidemiology
Singapore/epidemiology
Incidence
Adult
Aged, 80 and over
*Vision Disorders/epidemiology/ethnology
*Eye Diseases/epidemiology/ethnology
*Asian People/statistics & numerical data
Risk Factors
Cataract/epidemiology

@article {pmid41305085,
year = {2025},
author = {Wang, MH},
title = {Explainable Artificial Intelligence Framework for Predicting Treatment Outcomes in Age-Related Macular Degeneration.},
journal = {Sensors (Basel, Switzerland)},
volume = {25},
number = {22},
pages = {},
pmid = {41305085},
issn = {1424-8220},
support = {82501368//National Natural Science Foundation of China/ ; },
mesh = {Humans ; *Macular Degeneration/therapy/diagnostic imaging/diagnosis ; Aged ; *Artificial Intelligence ; Male ; Female ; Treatment Outcome ; Tomography, Optical Coherence ; Middle Aged ; Prognosis ; Deep Learning ; Fluorescein Angiography ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, yet current tools for forecasting treatment outcomes remain limited by either the opacity of deep learning or the rigidity of rule-based systems. To address this gap, we propose a hybrid neuro-symbolic and large language model (LLM) framework that combines mechanistic disease knowledge with multimodal ophthalmic data for explainable AMD treatment prognosis. In a pilot cohort of ten surgically managed AMD patients (six men, four women; mean age 67.8 ± 6.3 years), we collected 30 structured clinical documents and 100 paired imaging series (optical coherence tomography, fundus fluorescein angiography, scanning laser ophthalmoscopy, and ocular/superficial B-scan ultrasonography). Texts were semantically annotated and mapped to standardized ontologies, while images underwent rigorous DICOM-based quality control, lesion segmentation, and quantitative biomarker extraction. A domain-specific ophthalmic knowledge graph encoded causal disease and treatment relationships, enabling neuro-symbolic reasoning to constrain and guide neural feature learning. An LLM fine-tuned on ophthalmology literature and electronic health records ingested structured biomarkers and longitudinal clinical narratives through multimodal clinical-profile prompts, producing natural-language risk explanations with explicit evidence citations. On an independent test set, the hybrid model achieved AUROC 0.94 ± 0.03, AUPRC 0.92 ± 0.04, and a Brier score of 0.07, significantly outperforming purely neural and classical Cox regression baselines (p ≤ 0.01). Explainability metrics showed that >85% of predictions were supported by high-confidence knowledge-graph rules, and >90% of generated narratives accurately cited key biomarkers. A detailed case study demonstrated real-time, individualized risk stratification-for example, predicting an >70% probability of requiring three or more anti-VEGF injections within 12 months and a ~45% risk of chronic macular edema if therapy lapsed-with predictions matching the observed clinical course. These results highlight the framework's ability to integrate multimodal evidence, provide transparent causal reasoning, and support personalized treatment planning. While limited by single-center scope and short-term follow-up, this work establishes a scalable, privacy-aware, and regulator-ready template for explainable, next-generation decision support in AMD management, with potential for expansion to larger, device-diverse cohorts and other complex retinal diseases.},
}

Humans
*Macular Degeneration/therapy/diagnostic imaging/diagnosis
Aged
*Artificial Intelligence
Male
Female
Treatment Outcome
Tomography, Optical Coherence
Middle Aged
Prognosis
Deep Learning
Fluorescein Angiography

@article {pmid41304869,
year = {2025},
author = {Alali, NM and Aljahdali, A and AlBalawi, HB and Al Jarallah, OJ and Al Zaid, SM and Abuallut, I and ALMarek, F and Shajry, I and Alotaibi, YA and Hazzazi, MA and Magliyah, MS},
title = {Effectiveness, Safety, and Real-World Experience of Brolucizumab: A Systematic Review.},
journal = {Pharmaceuticals (Basel, Switzerland)},
volume = {18},
number = {11},
pages = {},
pmid = {41304869},
issn = {1424-8247},
abstract = {Background/Objectives: Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of approximately 26 kilodaltons (scFv, ~26 kDa) targeting all VEGF-A isoforms. Intravitreal brolucizumab (6 mg) is FDA-approved for neovascular age-related macular degeneration (nAMD) (2019) and diabetic macular edema (DME) (2022). We systematically review the literature on brolucizumab for nAMD and DME, focusing on efficacy, safety, pharmacokinetics, real-world outcomes, and cost-effectiveness in adult and pediatric patients. Methods: Our method involves a comprehensive literature search of PubMed, Embase, Scopus, Cochrane, and related databases (through late 2024) using terms including "brolucizumab," "Beovu," "neovascular AMD," "diabetic macular edema," "safety," "pharmacokinetics," and "pediatric." High-quality clinical trials, meta-analyses, regulatory documents, and real-world studies were prioritized. Results: In pivotal Phase III trials (HAWK/HARRIER for nAMD), brolucizumab 6 mg demonstrated non-inferior visual acuity (VA) gains to aflibercept, with >50% of eyes maintained on 12-week dosing and greater retinal fluid reduction. In DME trials (KESTREL/KITE), brolucizumab was similarly non-inferior to aflibercept for VA and showed superior anatomic drying, with 33-48% of eyes maintained on ≥12-week intervals. However, brolucizumab use has been associated with intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion: clinical trials and post hoc analyses reported higher rates of these events than comparator agents. Real-world cohorts found IOI in ~4-10% of treated eyes, often occurring early (within 3 months) after initiation. Conclusions: In conclusion, Brolucizumab is an effective anti-VEGF option for nAMD and DME, providing durable anatomic control with fewer injections. Non-inferior vision outcomes and superior fluid resolution have been demonstrated. However, it carries a distinct risk of IOI and occlusive vasculitis, necessitating careful patient selection, dosing, and monitoring.},
}

@article {pmid41303866,
year = {2025},
author = {Kang, SG and Singh, M and Lee, G and Lee, KE and Vinayagam, R},
title = {Formulation of α-Linolenic Acid-Based Microemulsions for Age-Related Macular Degeneration: Physicochemical Tests and HET-CAM Assays for Anti-Angiogenic Activities.},
journal = {Medicina (Kaunas, Lithuania)},
volume = {61},
number = {11},
pages = {},
pmid = {41303866},
issn = {1648-9144},
support = {1345370673, LINC3.0-2023-54//Ministry of Education and National Research Foundation of Korea/ ; },
mesh = {Emulsions/therapeutic use ; *alpha-Linolenic Acid/therapeutic use/pharmacology ; Animals ; *Angiogenesis Inhibitors/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy ; Chorioallantoic Membrane/drug effects ; Humans ; Chick Embryo ; Drug Delivery Systems/methods ; Chickens ; Mice ; Intravitreal Injections/methods ; },
abstract = {Background and Objectives: Age-related macular degeneration (AMD) is an age-associated retinal disorder characterized by blood-retinal barrier (BRB) breakdown and pathological angiogenesis, leading to vascular leakage. The intravitreal administration of anti-VEGF agents remains the most effective treatment for neovascular AMD. However, repetitive intravitreal injections have risks, causing side effects such as cataracts, bleeding, retina damage, and, in severe cases, post-injection endophthalmitis. Hence, the development of innovative drug delivery systems is essential to minimize the risks and discomfort associated with intravitreal injections. Materials and Methods: We developed a microemulsion (ME)-based topical drug delivery system incorporating α-linolenic acid (ALA). In brief, pseudo-ternary phase diagrams were constructed by the water titration method using different combinations of surfactants and cosurfactants (Smix-Cremophor RH 40: Span 80: Transcutol P in ratios of 1:1.05, 1:1:1, 1:1:1.5) containing ALA as the oil phase. Three blank microemulsions (ME1, ME2, and ME3) were prepared and characterized based on the optimized pseudo-ternary phase equilibrium with a Smix ratio of 1:1:1. Results: ME3, with an average particle size of 38.59 nm, was selected as the optimized formulation for developing drug-loaded ME containing Fenofibrate, Axitinib, and Sirolimus. The drug-loaded ME showed particle size (46.94-56.39 nm) and in vitro release displayed sustained and longer time drug release for 240 h. The irritation and antiangiogenic activities were evaluated using the hen's egg chorioallantoic membrane (HET-CAM) assay employing the optimized ME loaded with each drug. Among the three drug-loaded ME, the Sirolimus ME showed a reduction in blood vessel sprouting in the HET-CAM assay, indicating strong antiangiogenic activity. Treatment with the optimized blank ME and Sirolimus ME significantly (p < 0.05) reduced COX-2 protein expression in LPS-stimulated RAW 264.7 cells, suggesting their potential anti-inflammatory effects. Conclusions: Overall, we suggest that the α-linolenic acid-based Sirolimus microemulsion may serve as a promising topical therapeutic approach for managing AMD and offering a potential alternative to invasive intravitreal injections.},
}

Emulsions/therapeutic use
*alpha-Linolenic Acid/therapeutic use/pharmacology
Animals
*Angiogenesis Inhibitors/therapeutic use/pharmacology
*Macular Degeneration/drug therapy
Chorioallantoic Membrane/drug effects
Humans
Chick Embryo
Drug Delivery Systems/methods
Chickens
Mice
Intravitreal Injections/methods

@article {pmid41303411,
year = {2025},
author = {Gyenes, A and István, L and Papp, A and Resch, M and Récsán, Z and Ecsedy, M and Szepessy, Z and Szabó, A and Lesch, B and Barcsay, G and Borbándy, Á and Sándor, GL and Nagy, ZZ and Kovács, I},
title = {Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303411},
issn = {1422-0067},
mesh = {Humans ; *Visual Acuity/drug effects ; *Ranibizumab/therapeutic use/administration & dosage ; Male ; Female ; *Recombinant Fusion Proteins/therapeutic use/administration & dosage ; Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration & dosage ; Aged ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Macular Degeneration/drug therapy/physiopathology ; Retrospective Studies ; *Angiogenesis Inhibitors/therapeutic use/administration & dosage ; Intravitreal Injections ; Aged, 80 and over ; Treatment Outcome ; Middle Aged ; },
abstract = {The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate 'time in range' (TIR). TIR is defined as 'time spent with best-corrected visual acuity (BCVA) better than 20/40' and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05-1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action.},
}

Humans
*Visual Acuity/drug effects
*Ranibizumab/therapeutic use/administration & dosage
Male
Female
*Recombinant Fusion Proteins/therapeutic use/administration & dosage
Receptors, Vascular Endothelial Growth Factor/therapeutic use/administration & dosage
Aged
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Macular Degeneration/drug therapy/physiopathology
Retrospective Studies
*Angiogenesis Inhibitors/therapeutic use/administration & dosage
Intravitreal Injections
Aged, 80 and over
Treatment Outcome
Middle Aged

@article {pmid41303406,
year = {2025},
author = {Chao, WW and Chao, HW and Peng, PH and Lee, YT and Chao, HM},
title = {Retinal Ischemia: Therapeutic Effects and Mechanisms of Paeoniflorin.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303406},
issn = {1422-0067},
mesh = {Animals ; *Glucosides/pharmacology/therapeutic use ; *Monoterpenes/pharmacology/therapeutic use ; Rats ; Rats, Wistar ; Male ; Vascular Endothelial Growth Factor A/metabolism ; *Ischemia/drug therapy/metabolism/pathology ; Disease Models, Animal ; Retinal Pigment Epithelium/drug effects/metabolism/pathology ; *Retinal Diseases/drug therapy/metabolism/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Cell Survival/drug effects ; Reperfusion Injury/drug therapy/metabolism/pathology ; Apoptosis/drug effects ; Neuroprotective Agents/pharmacology ; },
abstract = {Retinal ischemia is a key factor in the progression of vision-threatening ocular diseases, including central retinal artery/vein occlusion, exudative age-related macular degeneration (eAMD), and proliferative diabetic retinopathy. This study investigates the effects of paeoniflorin along with its related neuroprotective molecular pathways in the treatment of retinal ischemia. Free radical or ischemic-like damage was induced by incubating retinal pigment epithelium (RPE) cells for 24 h with 1 mM hydrogen peroxide (H2O2) or by subjecting retinal neuronal cells to 8 h of oxygen-glucose deprivation (OGD). Both treatments caused significant cell loss. Treatment with paeoniflorin significantly increased cell viability at 0.5 mM in both cell types. In a Wistar rat model of retinal ischemia and reperfusion (I/R) elicited by sustained high intraocular pressure (HIOP), pre-treatment with 0.5 mM paeoniflorin mitigated the ischemia-induced decline in ERG b-wave amplitude, reduction in whole and inner retinal thickness, loss of fluorogold-labeled retinal ganglion cells, and formation of apoptotic cells. Meanwhile, paeoniflorin effectively downregulated pro-neovascular mediators β-catenin, hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), and the pro-inflammatory/angiogenic biomarker angiopoietin-2 (Ang-2), producing effects similar to the Wnt/β-catenin inhibitor (dickkopf-related protein 1), anti-angiogenic pigment epithelium-derived factor (PEDF), and anti-VEGF Avastin (bevacizumab). These findings suggest that paeoniflorin may protect against retinal ischemia through its anti-inflammatory, anti-neovascular/angiogenic, antioxidative, and neuroprotective properties.},
}

Animals
*Glucosides/pharmacology/therapeutic use
*Monoterpenes/pharmacology/therapeutic use
Rats
Rats, Wistar
Male
Vascular Endothelial Growth Factor A/metabolism
*Ischemia/drug therapy/metabolism/pathology
Disease Models, Animal
Retinal Pigment Epithelium/drug effects/metabolism/pathology
*Retinal Diseases/drug therapy/metabolism/pathology
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
Cell Survival/drug effects
Reperfusion Injury/drug therapy/metabolism/pathology
Apoptosis/drug effects
Neuroprotective Agents/pharmacology

@article {pmid41303405,
year = {2025},
author = {Noreen, S and Lim, SS and Lee, D},
title = {Preventive and Protective Effects of Nicotinamide Adenine Dinucleotide Boosters in Aging and Retinal Diseases.},
journal = {International journal of molecular sciences},
volume = {26},
number = {22},
pages = {},
pmid = {41303405},
issn = {1422-0067},
support = {RS-2021-NR060133//NRF/ ; },
mesh = {Humans ; *NAD/metabolism ; Animals ; *Aging/metabolism/drug effects ; *Retinal Diseases/metabolism/prevention & control/drug therapy ; Niacinamide/analogs & derivatives/pharmacology/therapeutic use ; Diabetic Retinopathy/metabolism/drug therapy/prevention & control ; Macular Degeneration/metabolism/drug therapy ; Mitochondria/metabolism/drug effects ; Retina/metabolism/drug effects ; Oxidative Stress/drug effects ; *Protective Agents/pharmacology ; Nicotinamide Mononucleotide/pharmacology/therapeutic use ; Pyridinium Compounds ; },
abstract = {Nicotinamide adenine dinucleotide (NAD[+]) boosting can sustain energy metabolism and neurovascular stability in the retinal tissue. Depletion of NAD[+] is linked to the development of pathological retinal conditions, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Mitochondrial dysfunction, oxidative stress, and inflammation occur in these diseases. This review summarizes substantial evidence of therapeutic NAD[+] boosters, including nicotinamide, nicotinamide mononucleotide, or nicotinamide riboside. They help improve mitochondrial function and lessen neurovascular injury. We also emphasize the importance of natural products and sirtuins in facilitating cytoprotective effects through the regulation of mitochondrial balance and inflammation. Developments in drug delivery methods, such as nanoparticle encapsulation and targeted eye treatments, are promising for enhancing the bioavailability and effectiveness of NAD[+] boosters. The novelty of this work is its combination of mechanistic insights regarding NAD[+] metabolism with efficacy data from preclinical studies. Furthermore, natural products may work together to boost their therapeutic effects against retinal damage. Together, our review article highlights NAD[+] metabolism as a potential therapeutic target for addressing retinal degeneration and maintaining vision in aging, neurologic disorders, and various metabolic diseases, including diabetes.},
}

Humans
*NAD/metabolism
Animals
*Aging/metabolism/drug effects
*Retinal Diseases/metabolism/prevention & control/drug therapy
Niacinamide/analogs & derivatives/pharmacology/therapeutic use
Diabetic Retinopathy/metabolism/drug therapy/prevention & control
Macular Degeneration/metabolism/drug therapy
Mitochondria/metabolism/drug effects
Retina/metabolism/drug effects
Oxidative Stress/drug effects
*Protective Agents/pharmacology
Nicotinamide Mononucleotide/pharmacology/therapeutic use
Pyridinium Compounds

@article {pmid41303260,
year = {2025},
author = {Lee, SY and Hwang, DD},
title = {Short-Term Effects of Intravitreal Ranibizumab Biosimilar Injections in Patients with Neovascular Age-Related Macular Degeneration on Retinal Nerve Fiber Layer Thickness.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41303260},
issn = {2077-0383},
abstract = {Background/Objectives: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD), but concerns remain regarding its potential effects on optic nerve structure. Evidence on the structural safety of ranibizumab biosimilars, including LucenBS[®], is still limited. This study aimed to investigate the short-term effects of intravitreal LucenBS[®] injections on peripapillary retinal nerve fiber layer (RNFL) thickness in previously treated nAMD patients using optical coherence tomography (OCT). Methods: This retrospective, observational case series included 24 eyes from 24 nAMD patients who had previously received anti-VEGF agents other than ranibizumab biosimilar. In bilateral cases, the eye that developed nAMD earlier was selected. Patients received between one and three LucenBS[®] injections, and the mean follow-up period after the final injection was 11.92 ± 4.81 weeks. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and peripapillary RNFL thickness were assessed before and after each injection using spectral-domain OCT. Sectoral and global RNFL values were compared using the Wilcoxon signed-rank test. Results: The mean age of participants was 74.6 ± 9.0 years, and baseline BCVA and IOP were 0.83 ± 0.66 logMAR and 14.88 ± 2.80 mmHg, respectively. RNFL thickness showed no significant changes in either global or sectoral regions after any injection (all p > 0.05). CMT significantly decreased after the first injection (p = 0.007), but remained stable with subsequent treatments. BCVA remained stable after the first and second injections, but slightly worsened after the third injection (p = 0.012). IOP showed no significant changes at any time point. Conclusions: Short-term intravitreal LucenBS[®] injections did not induce structural alterations in the peripapillary RNFL, supporting their short-term ocular safety in previously treated nAMD patients. Although CMT improved after the first injection, functional and anatomical responses varied with repeated dosing. Larger, long-term studies are required to further validate the structural and functional safety of ranibizumab biosimilars in nAMD management.},
}

@article {pmid41303214,
year = {2025},
author = {Wu, KY and Qian, SY and Camiré, A and Kim, DT and Giunta, M},
title = {Aflibercept for Wet Age-Related Macular Degeneration: A Prospective, Randomized Trial Comparing Treat-And-Extend and Fixed Bimonthly Dosing.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41303214},
issn = {2077-0383},
support = {Unknown//Bayer (Canada)/ ; },
abstract = {Background/Objectives: Currently, treatments for age-related macular degeneration (AMD) consist of regular intravitreal injections that exert significant pressure on healthcare systems via their high labor costs and economic burden. To address this, our study's goal is to propose new treatment protocols by comparing the efficacy of bimonthly fixed dosing aflibercept injections versus the treat-and-extend (T&E) approach for wet AMD. Secondary objectives included categorical best-corrected visual acuity (BCVA) changes, anatomical outcomes, treatment intervals, and adverse events. Methods: This study is a 1-year randomized, open-label, prospective trial that included 44 eyes from 44 patients, 32 in the T&E arm and 12 in the bimonthly arm. Treatment-naïve AMD patients with neovascularization were randomized to a bimonthly fixed dosing group or a T&E group after receiving 3 consecutive monthly aflibercept injections. Following the induction doses, retreatment intervals for patients in the T&E arm were adjusted based on a predetermined algorithm. Results: Over 12 months, mean BCVA improvements were 5.0 letters in the bimonthly group and 4.1 in the T&E group (p = 0.096 for non-inferiority test). On average, T&E patients received 9.6 injections compared to 7.7 for those in the fixed dosing group (p < 0.001). Anatomical outcomes were comparable in both treatment arms. Conclusions: In our trial, the T&E approach provided significant visual improvements, but did not meet the threshold for non-inferiority when compared to fixed bimonthly dosing. It was also unable to minimize treatment burden over the course of the first year of injections. Further research is required to optimize the T&E algorithm with aflibercept.},
}

@article {pmid41302976,
year = {2025},
author = {Molin, C and Midena, E and Convento, E and Midena, G and Pilotto, E},
title = {Fixation Stability as a Surrogate for Reading Abilities in Age-Related Macular Degeneration: A Perspective.},
journal = {Journal of clinical medicine},
volume = {14},
number = {22},
pages = {},
pmid = {41302976},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) significantly impacts central vision, fixation site and stability and reading abilities. This work aims to analyze the relationship between retinal fixation parameters measured using microperimetry and reading performance in patients with AMD. We identified the role of fixation stability measurement in the evaluation of reading abilities and discussed its implications both in clinical practice and in clinical trials. Our analysis highlights the importance of retinal fixation assessment as a precise surrogate for evaluating reading ability outcomes in AMD patients and as new clinical endpoint to demonstrate the functional effects of present and emerging target therapies.},
}

@article {pmid41302082,
year = {2025},
author = {Liesenhoff, C and Meyrl, C and Krause, D and Eckardt, F and Lorger, A and Deiters, V and Schiefelbein, J and Klaas, JE and Schworm, B and Priglinger, SG and Siedlecki, J},
title = {High-Dose 8 mg Aflibercept for Neovascular Age-Related Macular Degeneration: Who Is Being Treated with This New Agent?.},
journal = {Life (Basel, Switzerland)},
volume = {15},
number = {11},
pages = {},
pmid = {41302082},
issn = {2075-1729},
abstract = {Purpose: To describe the indication spectrum for high-dose 8 mg aflibercept for neovascular age-related macular degeneration (nAMD) in a real-world cohort in a tertiary referral center. Methods: The database of the University Eye Hospital Munich, Ludwig Maximilians-University was screened for eyes with nAMD treated with 8 mg aflibercept. Demographic data, multimodal imaging and treatment parameters were recorded. Reasons for treatment with 8 mg aflibercept were analyzed. Results: Thirty-four consecutive eyes of 31 patients (mean age 78.6 ± 8.9 years) were identified. There were 22 women (70.1%) and 9 men (29.9%). In all eyes (100%), 8 mg Aflibercept was applied as switching therapy. Prior to switching, the mean anti-vascular endothelial growth factor (VEGF) treatment duration for nAMD was 3.9 ± 2.9 years, pretreatment amounted to a mean of 34.5 ± 26.3 injections, equaling 9.2 ± 2.4 injections/year, and the mean visual acuity (VA) was 0.4 ± 0.4 logMAR. The last treatment before switching was 2 mg aflibercept in 76%, faricimab in 18%, ranibizumab in 3% and bevacizumab in 3% of cases. Reasons for switching included (A) recalcitrant nAMD with persistent fluid despite q4w dosing (17 eyes, 50%), (B) the wish for interval extension (15 eyes, 44%) and (C) macular hemorrhage (2 eyes, 6%). In group B, two-thirds of eyes (10/15, 66.7%) were maintained at ≤q6w prior to switching. Conclusions: In this study, high-dose 8 mg aflibercept was exclusively used as a switch therapy. Most eyes (76%) switched were from pretreatment with 2 mg aflibercept. The main reasons for switching were recalcitrant nAMD with persistent fluid despite q4w dosing (50%) or the wish for treatment extension beyond 6 weeks (32%). In the future, these data will aid in the design of prospective real-world studies comparing the efficacy of high-dose 8 mg aflibercept with older generation treatment options, especially 2 mg aflibercept.},
}

@article {pmid41301918,
year = {2025},
author = {Lee, Y and Seo, JH},
title = {Potential Causal Effects of Cystatin C on Age-Related Macular Degeneration: A Two-Sample Mendelian Randomization Study.},
journal = {Biomedicines},
volume = {13},
number = {11},
pages = {},
pmid = {41301918},
issn = {2227-9059},
support = {VHSMC24002//Veterans Health Service Medical Center Research Grant/ ; },
abstract = {Background/Objectives: Previous studies have shown an association between kidney function and age-related macular degeneration (AMD). This study aims to assess whether the kidney function-related parameters of serum cystatin C and creatinine levels are associated with increased risk of AMD and its subtypes. Methods: Genetic instruments for variants associated with serum cystatin C and creatinine levels as exposure at genome-wide significance (p < 5.0 × 10[-8]) were obtained from the UK Biobank. Genetic data for AMD and its subtypes were obtained from the FinnGen project. A two-sample Mendelian randomization analysis was performed to evaluate the causal effects of serum cystatin C and creatinine levels on AMD and its subtypes. Results: Using an inverse-variance weighted approach, higher cystatin C levels are associated with an increased risk of AMD [odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.04 to 1.22, p = 0.004 for overall AMD; OR = 1.14, 95% CI: 1.04 to 1.25, p = 0.007 for dry AMD; OR = 1.14, 95% CI: 1.03 to 1.26, p = 0.011 for wet AMD]. However, serum creatinine levels did not significantly impact the risk of AMD or its subtypes. Conclusions: This study provides genetic evidence that higher cystatin C levels may be a causal risk factor for AMD and its subtypes, whereas serum creatinine was not. This result implies the need to investigate the effect of cystatin C on AMD potentially independent of kidney function.},
}

@article {pmid41301509,
year = {2025},
author = {Nardella, M and Pellegrini, M and Yu, AC and Adamo, GG and Mura, M and Busin, M},
title = {Nanotechnology-Based Delivery Systems and Retinal Pigment Epithelium: Advances, Targeting Approaches, and Translational Challenges.},
journal = {Biomolecules},
volume = {15},
number = {11},
pages = {},
pmid = {41301509},
issn = {2218-273X},
mesh = {Humans ; *Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Drug Delivery Systems/methods ; Animals ; *Nanotechnology/methods ; Translational Research, Biomedical ; Nanomedicine/methods ; Macular Degeneration/drug therapy ; Retinal Diseases/drug therapy ; Nanoparticles/chemistry ; },
abstract = {The retinal pigment epithelium (RPE) is essential for maintaining retinal integrity, and its dysfunction underlies several progressive ocular diseases, including age-related macular degeneration, choroidal neovascularization (CNV), inherited retinal disorders (IRDs), and proliferative vitreoretinopathy (PVR). Although current therapies have improved disease management, they mainly target secondary pathological mechanisms and do not directly preserve or restore RPE function. Moreover, the delivery of therapeutic molecules or genes to the RPE remains a major challenge due to the presence of multiple ocular barriers and the need for sustained, localized action. Nanomedicine offers innovative solutions to these limitations by enabling precise, controlled, and cell-specific delivery of drugs and genetic materials. Engineered nanocarriers can be optimized to traverse ocular barriers, enhance bioavailability, and modulate the retinal microenvironment. This review summarizes recent advances in nanoscale delivery systems for RPE-targeted therapies, focusing on design principles, targeting strategies, and therapeutic applications, and discusses the translational challenges that must be addressed to bring nanotechnology-based treatments closer to clinical application.},
}

Humans
*Retinal Pigment Epithelium/metabolism/drug effects/pathology
*Drug Delivery Systems/methods
Animals
*Nanotechnology/methods
Translational Research, Biomedical
Nanomedicine/methods
Macular Degeneration/drug therapy
Retinal Diseases/drug therapy
Nanoparticles/chemistry

@article {pmid41301489,
year = {2025},
author = {Intonti, S and Olivieri, C and Reibaldi, M and Borrelli, E and Curcio, C and Conedera, FM},
title = {Translational Molecular and Fluid Biomarkers for Age-Related Macular Degeneration: Practical Insights from Animal Models and Humans.},
journal = {Biomolecules},
volume = {15},
number = {11},
pages = {},
pmid = {41301489},
issn = {2218-273X},
support = {PZ00P3_223803/SNSF_/Swiss National Science Foundation/Switzerland ; },
mesh = {Humans ; *Biomarkers/metabolism ; Animals ; *Macular Degeneration/metabolism/diagnosis/pathology/genetics ; Disease Models, Animal ; Oxidative Stress ; Mice ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss. Its pathogenesis is complex and multifactorial, involving genetic predisposition, inflammation, oxidative stress, and environmental influences, which underscores the need to better understand biomarkers associated with the disease. This review provides a comprehensive translational overview of biomarkers linked to both dry and wet forms of AMD by integrating findings from human studies and preclinical mouse models, including chemical, genetic, and laser-induced paradigms. It outlines key tissue, fluid, and systemic biomarkers related to oxidative stress, inflammation, complement activation, extracellular matrix remodeling, angiogenesis, and gut microbiota alterations. The main findings highlight similarities and differences between human AMD and animal models, identify challenges in biomarker validation, and emphasize the potential of combining biomarker profiles from ocular tissues, blood, tear fluid, aqueous and vitreous humor, and gut microbiome samples to improve early diagnosis, therapeutic monitoring, and personalized treatment strategies. These insights suggest that integrating experimental and clinical biomarker data could advance precision medicine in AMD, facilitating better early detection and individualized therapies. Future research should aim to bridge these datasets to optimize biomarker-driven approaches for AMD management.},
}

Humans
*Biomarkers/metabolism
Animals
*Macular Degeneration/metabolism/diagnosis/pathology/genetics
Disease Models, Animal
Oxidative Stress
Mice

@article {pmid41300437,
year = {2025},
author = {Hong, SJ and Lee, DH and Choi, JW and Lee, H and Sung, Y and Kim, GJ},
title = {Nrf2 Activated by PD-MSCs Attenuates Oxidative Stress in a Hydrogen Peroxide-Injured Retinal Pigment Epithelial Cell Line.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {11},
pages = {},
pmid = {41300437},
issn = {2076-3921},
support = {RS - 2025 - 431 02313877//Industry - Academia - Research Institute (IAR) Collabo R&D Fund Grant funded by the Korean Government/ ; },
abstract = {Age-related macular degeneration (AMD) is a retinal degenerative disease caused by oxidative stress. Thus, we aimed to reduce oxidative stress through the use of placenta-derived mesenchymal stem cells (PD-MSCs). To induce oxidative stress in ARPE-19 cells, we treated them with 200 µM hydrogen peroxide (H2O2) for 2 h and then cocultured them with PD-MSCs. The dissociation of the KEAP1/Nrf2 complex, along with the expression of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT), increased in the coculture group compared with the H2O2 treatment group (* p < 0.05). The expression levels of antioxidant genes increased in the cocultured group compared with those in the H2O2 treatment group (* p < 0.05), whereas the ROS levels decreased in the cocultured group (* p < 0.05). Additionally, both the expression of mitochondrial dynamics markers and the mitochondrial membrane potential increased when the cells were cocultured with PD-MSCs (* p < 0.05). PD-MSC cocultivation decreased the expression levels of lipoproteins (* p < 0.05). Finally, we confirmed that PD-MSCs promoted the expression of RPE-specific genes in H2O2-injured ARPE-19 cells (* p < 0.05). These findings suggest a new aspect of stem cell treatment for AMD induced by oxidative stress.},
}

@article {pmid41300254,
year = {2025},
author = {Shi, C and Lee, J and Shi, D and Wang, G and Yuan, F and Lai, TYY and Liu, J and Lu, Y and Liu, D and Qin, B and Zee, BC},
title = {AI-Based Retinal Image Analysis for the Detection of Choroidal Neovascular Age-Related Macular Degeneration (AMD) and Its Association with Brain Health.},
journal = {Brain sciences},
volume = {15},
number = {11},
pages = {},
pmid = {41300254},
issn = {2076-3425},
abstract = {Purpose: This study aims to develop a method for detecting referable (intermediate and advanced) age-related macular degeneration (AMD) and neovascular AMD, as well as providing an automatic segmentation of choroidal neovascularisation (CNV) on colour fundus retinal images. We also demonstrated that brain health risk scores estimated by AI-based Retinal Image Analysis (ARIA), such as white matter hyperintensities and depression, are significantly associated with AMD and neovascular AMD. Methods: A primary dataset of 1480 retinal images was collected from Zhongshan Hospital of Fudan University for training and 10-fold cross-validation. Additionally, two validation subdataset comprising 238 images (retinal images and wide-field images) were used. Using fluorescein angiography-based labels, we applied the InceptionResNetV2 deep network with the ARIA method to detect AMD, and a transfer ResNet50_Unet was used to segment CNV. The risks of cerebral white matter hyperintensities and depression were estimated using an AI-based Retinal Image Analysis approach. Results: In a 10-fold cross-validation, we achieved sensitivities of 97.4% and 98.1%, specificities of 96.8% and 96.1%, and accuracies of 97.0% and 96.4% in detecting referable AMD and neovascular AMD, respectively. In the external validation, we achieved accuracies of 92.9% and 93.7% and AUCs of 0.967 and 0.967, respectively. The performances on two validation sub-datasets show no statistically significant difference in detecting referable AMD (p = 0.704) and neovascular AMD (p = 0.213). In the segmentation of CNV, we achieved a global accuracy of 93.03%, a mean accuracy of 91.83%, a mean intersection over union (IoU) of 68.7%, a weighted IoU of 89.63%, and a mean boundary F1 (BF) of 67.77%. Conclusions: The proposed method shows promising results as a highly efficient and cost-effective screening tool for detecting neovascular and referable AMD on both retinal and wide-field images, and providing critical insights into CNV. Its implementation could be particularly valuable in resource-limited settings, enabling timely referrals, enhancing patient care, and supporting decision-making across AMD classifications. In addition, we demonstrated that AMD and neovascular AMD are significantly associated with increased risks of WMH and depression.},
}

@article {pmid41297526,
year = {2025},
author = {Paneerselvam, GS and Wai, NJ and Sheng, LJ and Kenneth, LKC},
title = {Cost-Effectiveness of Vascular Endothelial Growth Factor Inhibitors in the Management of Wet Age-Related Macular Degeneration: A Systematic Review.},
journal = {Value in health regional issues},
volume = {53},
number = {},
pages = {101542},
doi = {10.1016/j.vhri.2025.101542},
pmid = {41297526},
issn = {2212-1102},
abstract = {OBJECTIVES: To evaluate the cost-effectiveness of VEGF inhibitors, ranibizumab, aflibercept, bevacizumab, brolucizumab, pegaptanib, and conbercept for wAMD treatment.

METHODS: A systematic search was conducted in PubMed, Cochrane, and SpringerLink databases to identify cost-effectiveness analyses and cost-utility analyses related to wAMD treatment. Eligible studies were assessed using Drummond's 10-point checklist to evaluate methodological quality. The extracted data included intervention costs, quality-adjusted life-years, and incremental cost-effectiveness ratios.

RESULTS: Twenty-two studies met the inclusion criteria. Bevacizumab and brolucizumab were frequently reported as cost-effective alternatives, offering comparable or superior visual outcomes at lower costs than ranibizumab or aflibercept. Pegaptanib was consistently less cost-effective. Findings for ranibizumab versus aflibercept varied by treatment regimen and analytic assumptions. Across studies, cost-effectiveness estimates were influenced by model perspective, time horizon, exclusion of adverse events, and single-eye modeling. A further limitation is that in contexts of non-inferior efficacy, small incremental quality-adjusted life-years differences may artificially inflate incremental cost-effectiveness ratios, potentially overstating the costs relative to benefits.

CONCLUSIONS: Decision making in wAMD treatment requires more thorough economic evaluations that incorporate standardized methodologies and lengthy cost assessments.},
}

@article {pmid41297424,
year = {2025},
author = {Zhou, L and Ma, Y and Li, X and Cao, G},
title = {Gut-eye axis in ophthalmic diseases: Focus on ocular neurodegeneration.},
journal = {Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie},
volume = {193},
number = {},
pages = {118800},
doi = {10.1016/j.biopha.2025.118800},
pmid = {41297424},
issn = {1950-6007},
abstract = {Ocular neurodegeneration comprises a group of complex processes that severely affect visual function and is recognized as a key pathogenetic process in a variety of blinding ocular diseases, including glaucoma, diabetic retinopathy, age-related macular degeneration and retinitis pigmentosa. Although these diseases have different etiologies and mechanisms, apoptosis, metabolic disorders and oxidative damage are common features shared by all of them. Increasing evidence indicates that gut microbiota regulates distant organs by engaging in the host's neural, endocrine, immune regulation and even intercellular information. However，in ocular degenerative diseases, specific gut microbiota and their metabolites play an important role in ocular degenerative diseases. Therefore, in this review, we summarize the pathways through which the "gut-eye axis" functions and the mechanisms by which it interacts with ocular degenerative diseases, as well as the alterations in gut microbiota profiles observed in several common ocular degenerative diseases. Additionally, we provide an outlook on the clinical application of the "gut-eye axis", including its potential diagnostic, therapeutic, and adjunctive therapies.},
}

@article {pmid41294847,
year = {2025},
author = {Alam, J and Ponnam, A and Souvangini, A and Gopi, S and Ildefonso, CJ and Biswal, MR},
title = {EPO-R76E Enhances Retinal Pigment Epithelium Viability Under Mitochondrial Oxidative Stress Induced by Paraquat.},
journal = {Cells},
volume = {14},
number = {22},
pages = {},
pmid = {41294847},
issn = {2073-4409},
support = {R01 EY033415/EY/NEI NIH HHS/United States ; R01EY033415/EY/NEI NIH HHS/United States ; },
mesh = {*Oxidative Stress/drug effects ; *Retinal Pigment Epithelium/metabolism/pathology/drug effects ; Humans ; *Mitochondria/metabolism/drug effects ; *Paraquat/toxicity/pharmacology ; *Erythropoietin/genetics/metabolism ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Cell Line ; NF-E2-Related Factor 2/metabolism ; Apoptosis/drug effects ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, primarily driven by oxidative stress-induced degeneration of retinal pigment epithelium (RPE). Erythropoietin (EPO), a hematopoietic cytokine with neuroprotective properties, has been shown to reduce apoptosis and retinal degeneration. In this study, we examined the cytoprotective role of a non-erythropoietic EPO variant, EPO-R76E, in suppressing oxidative stress and mitochondrial dysfunction related to oxidative stress in RPE cells. Stable ARPE-19 cell lines expressing EPO-R76E were generated via lentiviral transduction and exposed to paraquat to induce oxidative stress. Oxidative stress was induced using paraquat. EPO-R76E expression conferred increased cell viability and resistance to mitochondrial damage, as assessed by cytotoxicity assays. Western blot analysis revealed reduced expression of ferritin and p62/SQSTM1, diminished activation of p-AMPK and NRF2, and restoration of GPX4 levels, indicating enhanced antioxidant defenses. Moreover, intracellular iron accumulation and reactive oxygen species were significantly reduced in EPO-R76E-expressing cells exposed to paraquat. These findings suggest that EPO-R76E promotes mitochondrial homeostasis and modulates oxidative stress pathways. Our study positions EPO-R76E as a promising therapeutic candidate for halting RPE degeneration in AMD.},
}

*Oxidative Stress/drug effects
*Retinal Pigment Epithelium/metabolism/pathology/drug effects
Humans
*Mitochondria/metabolism/drug effects
*Paraquat/toxicity/pharmacology
*Erythropoietin/genetics/metabolism
Cell Survival/drug effects
Reactive Oxygen Species/metabolism
Cell Line
NF-E2-Related Factor 2/metabolism
Apoptosis/drug effects

@article {pmid41294302,
year = {2025},
author = {Quarta, A and Corradetti, G and Romano, F and Trinco, A and Feo, A and Corvi, F and Nardi, C and Alhelaly, M and Abbasgholizadeh, R and Chujo, S and Popovic, M and Soylu, C and Chung, YC and Kwak, HD and Rattu, R and Nittala, MG and Staurenghi, G and Sadda, SR},
title = {Distinct Profiles of Choriocapillaris Involvement in Extensive Macular Atrophy With Pseudodrusen-Like Appearance and Geographic Atrophy.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {14},
pages = {64},
pmid = {41294302},
issn = {1552-5783},
mesh = {Humans ; *Geographic Atrophy/physiopathology/diagnosis/etiology ; Retrospective Studies ; Female ; *Choroid/blood supply ; Cross-Sectional Studies ; Male ; Tomography, Optical Coherence/methods ; Aged ; Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Drusen/diagnosis/physiopathology ; Capillaries/pathology/physiopathology ; *Macular Degeneration/complications/diagnosis/physiopathology ; Visual Acuity ; Fundus Oculi ; Middle Aged ; Regional Blood Flow/physiology ; },
abstract = {PURPOSE: To quantitatively compare choriocapillaris flow deficit percentages (CCFD%) between eyes with extensive macular atrophy with pseudodrusen-like appearance (EMAP) and geographic atrophy (GA) secondary to age-related macular degeneration (AMD), and to identify predictive factors for CCFD% at the atrophy margin.

METHODS: This retrospective cross-sectional study included 53 eyes (27 with GA and 26 with EMAP). CCFD% were computed within a 500-µm-wide marginal zone (CCFD%_M) and beyond the margin (CCFD%_BM) using compensated en face optical coherence tomography angiography (OCTA) images. Atrophy-to-fovea distance (AFD) was quantified by pixel-wise Euclidean analysis.

RESULTS: Eyes with EMAP demonstrated significantly higher CCFD% compared to GA both at the atrophy margin (CCFD%_M, P < 0.05) and beyond (CCFD%_BM, P < 0.01). In univariable analysis, belonging to the GA group was associated with a 5.9-unit reduction in CCFD%_M, reflecting a substantial preservation of choriocapillaris (CC) perfusion in GA relative to EMAP. AFD was greater in EMAP (2.35 ± 0.56 mm) than GA (1.74 ± 0.55 mm; P = 0.014) suggesting more eccentric positioning of the lesions in the former. A multivariable mixed-effects model confirmed disease subtype (EMAP vs. GA) as an independent determinant of CC impairment with EMAP associated with a significantly higher CCFD%_M (P < 0.01).

CONCLUSIONS: CC impairment is more pronounced in EMAP than in GA, with EMAP exhibiting more extensive and diffuse CCFD, particularly at the atrophy margins. This pattern may reflect a more aggressive vascular compromise in EMAP. These findings underscore a distinct CC pathoanatomy between the two conditions, with implications for disease progression and therapeutic targeting.},
}

Humans
*Geographic Atrophy/physiopathology/diagnosis/etiology
Retrospective Studies
Female
*Choroid/blood supply
Cross-Sectional Studies
Male
Tomography, Optical Coherence/methods
Aged
Fluorescein Angiography/methods
Aged, 80 and over
*Retinal Drusen/diagnosis/physiopathology
Capillaries/pathology/physiopathology
*Macular Degeneration/complications/diagnosis/physiopathology
Visual Acuity
Fundus Oculi
Middle Aged
Regional Blood Flow/physiology

@article {pmid41293996,
year = {2025},
author = {Xin, X and Zhao, X and Han, X and Pu, W},
title = {ASNS Regulates H2O2-Induced Senescence, Oxidative Stress, and Glucose Metabolism in ARPE-19 Cells by Modulating USP13 Expression.},
journal = {BioFactors (Oxford, England)},
volume = {51},
number = {6},
pages = {e70057},
pmid = {41293996},
issn = {1872-8081},
support = {2023GLLH0239//Science and Technology Program of the Joint Fund of Scientific Research for the Public Hospitals of InnerMongolia Academyof Medical Sciences/ ; 2023YK17//Scientific Research Program of Aerospace Medical and Healthcare Technology Group Co./ ; },
mesh = {Oxidative Stress/drug effects ; Humans ; Hydrogen Peroxide/pharmacology ; *Glucose/metabolism ; Cellular Senescence/drug effects ; Animals ; Cell Line ; Retinal Pigment Epithelium/metabolism/drug effects/pathology ; *Macular Degeneration/genetics/metabolism/pathology ; Cell Survival/drug effects ; Reactive Oxygen Species/metabolism ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a common degenerative disease of the eye that ultimately leads to irreversible vision loss. Asparagine synthase (ASNS) is an aminotransferase, and its low expression is associated with retinal damage. The present study centered on the protective effect of ASNS on retinal epithelial cells. We found that in the AMD cell model, overexpression of ASNS reduced SA-β-gal staining and ROS production, and increased cell viability in H2O2-treated ARPE-19 cells. In addition, overexpression of ASNS increased glucose consumption, lactate production, extracellular acidification rate (ECAR), and oxygen consumption rate (OCR) and enhanced the expression of glycolytic markers. Molecular mechanistic studies revealed that ASNS was highly bound to USP13 protein and increased USP13 expression. Furthermore, ASNS protected the retinal epithelium from oxidative stress damage in an animal model of AMD. Taken together, these findings suggest that the ASNS/USP13 axis plays an important regulatory role in AMD development. Our findings not only emphasized the understanding of the role of glucose metabolism in AMD, but also identified a promising target for future AMD therapy.},
}

Oxidative Stress/drug effects
Humans
Hydrogen Peroxide/pharmacology
*Glucose/metabolism
Cellular Senescence/drug effects
Animals
Cell Line
Retinal Pigment Epithelium/metabolism/drug effects/pathology
*Macular Degeneration/genetics/metabolism/pathology
Cell Survival/drug effects
Reactive Oxygen Species/metabolism
Disease Models, Animal

@article {pmid41293704,
year = {2025},
author = {Guo, Y and Hormel, TT and Wu, AL and Gao, M and Hwang, TS and Bailey, ST and Jia, Y},
title = {AI-aided segmentation of four types of drusen in volumetric OCT.},
journal = {Biomedical optics express},
volume = {16},
number = {11},
pages = {4380-4391},
pmid = {41293704},
issn = {2156-7085},
abstract = {Drusen are a hallmark biomarker of age-related macular degeneration (AMD), with their size, number, and morphology (type) closely linked to disease severity and progression. Accurate segmentation and classification of drusen from optical coherence tomography (OCT) images are essential for objective AMD assessment and monitoring. In this work, we present a deep learning framework that combines a convolutional neural network for automated drusen segmentation with a dedicated classification module to distinguish four clinically relevant, distinct drusen types based on segmentation output. We evaluated our approach on a comprehensive dataset and achieved a mean Dice score of 0.74 ± 0.21 for voxel-wise segmentation accuracy and a critical success index of 0.69 ± 0.24 for drusen count accuracy. This method demonstrates substantial improvements in the quantitative drusen analysis and offers a promising tool for enhanced AMD diagnosis and tracking of disease progression.},
}

@article {pmid41293061,
year = {2025},
author = {Lorenzi, M and Ebohon, S and Kissner, J and Comiskey, J and Paap, M and Bouchet, C and Garnham, A and Wissinger, E},
title = {Network Meta-Analysis of Bevacizumab Gamma Versus Competing Interventions for Treating Neovascular Age-Related Macular Degeneration in the United Kingdom.},
journal = {Journal of market access & health policy},
volume = {13},
number = {4},
pages = {58},
pmid = {41293061},
issn = {2001-6689},
abstract = {This study aimed to determine the relative efficacy of bevacizumab gamma (an ophthalmic formulation of bevacizumab) versus alternative interventions relevant to the treatment of neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) via a systematic literature review (SLR) and network meta-analysis (NMA). An SLR was conducted to identify randomized controlled trials (RCTs) of anti-vascular endothelial growth factor (anti-VEGF) therapies for the treatment of nAMD in adult patients relevant to the UK context. The included anti-VEGF treatments were ranibizumab, aflibercept, faricimab, and bevacizumab gamma. Bayesian NMA models were used to estimate relative efficacy in terms of change from baseline (CFB) in best-corrected visual acuity (BCVA) at 12 months, the proportion of patients gaining 15 or more letters at 12 months, and the proportion of patients losing less than 15 letters at 12 months. Twenty-two relevant RCTs were included in the NMA. At 12 months, all anti-VEGF treatments were similarly efficacious to ranibizumab 0.5 mg every four weeks (Q4W) in terms of CFB in BCVA, the proportion of patients gaining 15 or more letters, and the proportion of patients losing less than 15 letters (except for ranibizumab 0.5 mg every 12 weeks [Q12W] and ranibizumab 0.5 mg pro re nata [PRN]). Bevacizumab gamma provided similar improvements in visual acuity to other anti-VEGF treatments.},
}

@article {pmid41292308,
year = {2025},
author = {Kim, TR and Kim, TG and Choi, J and Yu, SY and Kim, K},
title = {Quantitative Analysis of Drusen in Korean Patients: A 36-Month Follow-Up Study.},
journal = {Korean journal of ophthalmology : KJO},
volume = {},
number = {},
pages = {},
doi = {10.3341/kjo.2025.0104},
pmid = {41292308},
issn = {2092-9382},
abstract = {PURPOSE: This study aimed to quantitatively evaluate longitudinal changes in drusen area and volume over 36 months in Korean patients and to identify the factors associated with these changes and the development of advanced age-related macular degeneration (AMD).

METHODS: In this retrospective study, 38 eyes from 38 patients diagnosed with drusen were analyzed. The drusen area and volume were measured using spectral-domain optical coherence tomography (SD-OCT, Cirrus 5000; Carl Zeiss Meditec, Dublin, CA, USA) with an automated retinal pigment epithelium (RPE) elevation map algorithm. To minimize bias from variable follow-up intervals, an annualized classification framework was adopted. Based on percentage change in drusen area within the 5-mm circle, eyes were categorized as progressed (increase >20%), stable (change within ±20%), or regressing (decrease >20%).

RESULTS: Both drusen area and volume increased significantly up to 24 months (area: p = 0.003; volume: p = 0.028) and then showed a modest decline at 36 months, remaining above baseline levels. No significant difference in the proportions of progressed, stable, or regressing eyes was observed across 12-month intervals or compared with baseline (all p > 0.05). A larger baseline 5-mm drusen area was significantly associated with the development of advanced AMD (adjusted odds ratio = 2.818; 95% confidence interval, 1.022-7.767; p = 0.045). Eyes that exhibited at least one episode of drusen regression showed a higher incidence of advanced AMD (36.8% vs 5.3%; p = 0.042).

CONCLUSIONS: Drusen in Korean patients demonstrated dynamic morphological remodeling over time. Drusen regression was not a benign phenomenon but rather a potential high-risk marker for progression to advanced AMD. These findings highlight the importance of population-specific, quantitative SD-OCT monitoring for early risk stratification in East Asian eyes.},
}

@article {pmid41284475,
year = {2025},
author = {Cui, Y and Song, Z and Wang, X},
title = {Bisphosphonate-related ocular adverse events: a pharmacovigilance study based on the FAERS database.},
journal = {Endocrine connections},
volume = {},
number = {},
pages = {},
doi = {10.1530/EC-25-0482},
pmid = {41284475},
issn = {2049-3614},
abstract = {This retrospective study aimed to identify and characterize signals of ocular adverse events (AEs) related to bisphosphonates (BPs) using FDA Adverse Event Reporting System (FAERS) data (2004Q1-2024Q3) to inform future safety investigations. Disproportionality analysis was conducted utilizing the reporting odds ratio (ROR), proportional reporting ratio (PRR), and Bayesian confidence propagation neural network (BCPNN) methods to identify BP-related ocular AE signals. Additionally, a modified ROR method was utilized to examine differences across gender and age. Among 6,965 ocular AE reports for five BPs (alendronate, zoledronate, pamidronate, risedronate, and ibandronate), 136 positive signals were identified, predominantly unlisted in drug labels. Notable risks included ocular inflammatory AEs (especially zoledronate) and novel risk signals such as cataract, glaucoma, and macular degeneration. Standardized MedDRA queries (SMQ) linked BPs to 11 eye disorders, with scleral disorders common to all five BPs and pamidronate involving the broadest SMQ categories. Ocular AEs for alendronate, zoledronate, and pamidronate exhibited age-related differences, while those for alendronate and zoledronate showed gender differences. This study identifies high-risk and novel ocular AEs related to BPs. These findings warrant further validation in future studies.},
}

@article {pmid41283579,
year = {2025},
author = {Cao, JA and Zhou, AW and Teagle, GM and Baumann, LM and Sahraravand, RA and Wong, CW and De Zanet, S and Jovic, N and Steiner, P and Patel, SB and Minaker, SA and MacCumber, MW and Brown, DM and Al-Khersan, H and Wykoff, CC},
title = {Geographic Atrophy Progression in Clinical Practice Before and After Pegcetacoplan Treatment.},
journal = {Vision (Basel, Switzerland)},
volume = {9},
number = {4},
pages = {},
pmid = {41283579},
issn = {2411-5150},
support = {N/A//Texas Retina Research Foundation (TRRF), Houston, Texas/ ; },
abstract = {This retrospective study evaluated changes in ocular characteristics and retinal pigment epithelium (RPE) and photoreceptor ellipsoid zone (EZ) depletion rates before and after intravitreal pegcetacoplan initiation in clinical practice. A total of 168 eyes from 110 patients with GA secondary to age-related macular degeneration (AMD) who received at least 3 pegcetacoplan injections were included. Data was collected from 5 years before to 9 months after pegcetacoplan initiation. RPE and EZ depletion areas were measured using an automated artificial intelligence (AI) algorithm on optical coherence tomography (OCT) images. At baseline, 76 eyes (45.2%) had concurrent neovascular AMD (nAMD), with mean RPE and EZ depletion areas of 3.3 mm[2] and 4.9 mm[2], respectively. By pegcetacoplan initiation, these increased to 8.6 mm[2] and 11.2 mm[2], respectively, with 151 eyes (89.9%) having concurrent nAMD and 155 eyes (92.3%) having subfoveal GA. Pre-treatment to post-treatment RPE and EZ square root depletion rates decreased from 0.25 mm/year to 0.096 mm/year, and 0.26 mm/year to 0.049 mm/year, respectively. Mean best-recorded visual acuity (BRVA) worsened by 0.05 logMAR annually before and after treatment. These real-world findings align with data from the pegcetacoplan phase 3 trials, showing reduced RPE and EZ depletion rates without changes in rates of BRVA loss. Additional studies are warranted.},
}

@article {pmid41283408,
year = {2025},
author = {Barranco Garcia, J and Ferrazzini, T and Coito, A and Brügger, D and Abegg, M},
title = {Recovery of the Pupillary Response After Light Adaptation Is Slowed in Patients with Age-Related Macular Degeneration.},
journal = {Journal of eye movement research},
volume = {18},
number = {6},
pages = {},
pmid = {41283408},
issn = {1995-8692},
abstract = {Purpose: This study evaluates a novel, non-invasive method using a virtual reality (VR) headset with integrated eye trackers to assess retinal function by measuring the recovery of the pupillary response after light adaptation in patients with age-related macular degeneration (AMD). Methods: In this pilot study, fourteen patients with clinically confirmed AMD and 14 age-matched healthy controls were exposed to alternating bright and dark stimuli using a VR headset. The dark stimulus duration increased incrementally by 100 milliseconds per trial, repeated over 50 cycles. The pupillary response to the re-onset of brightness was recorded. Data were analyzed using a linear mixed-effects model to compare recovery patterns between groups and a convolutional neural network to evaluate diagnostic accuracy. Results: The pupillary response amplitude increased with longer dark stimuli, i.e., the longer the eye was exposed to darkness the bigger was the subsequent pupillary amplitude. This pupillary recovery was significantly slowed by age and by the presence of macular degeneration. Test diagnostic accuracy for AMD was approximately 92%, with a sensitivity of 90% and a specificity of 70%. Conclusions: This proof-of-concept study demonstrates that consumer-grade VR headsets with integrated eye tracking can detect retinal dysfunction associated with AMD. The method offers a fast, accessible, and potentially scalable approach for retinal disease screening and monitoring. Further optimization and validation in larger cohorts are needed to confirm its clinical utility.},
}

@article {pmid41282784,
year = {2025},
author = {Zhang, PW and Wan, ZH and Liu, S and Wang, J and Sripathi, S and Li, W and Ahn, J and Li, S and Fan, L and Berlinicke, CA and Qian, J and Merbs, SL and Zack, DJ},
title = {HTRA1-AS1 , an ARMS2 -region long non-coding RNA, is downregulated in retinas of age-related macular degeneration patients.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282784},
abstract = {PURPOSE: The human 10q26 locus is a major genetic risk factor for age-related macular degeneration (AMD). Fine mapping by linkage and large-scale genome-wide association studies (GWAS) has narrowed this region to a 30-kb interval encompassing the ARMS2 and HTRA1 genes. However, the causative gene(s), risk variants, and underlying pathogenic mechanisms remain unresolved.

METHODS: Long non-coding RNA (lncRNA) candidates within the ARMS2-HTRA1 region were identified using human postmortem retinal RNA-seq data and public databases (NCBI, Ensembl). Candidate transcripts were validated by RT-PCR and Sanger sequencing. Published single-cell RNA-seq datasets were analysed to define cell type-specific expression, and RNA levels were compared between AMD and non-AMD donor retinas. Additionally, expression changes were assessed in human iPSC-derived retinal pigment epithelium (RPE) cells exposed to cigarette smoke extract (CSE) and paraquat (PQT).

RESULTS: We identified and validated a lncRNA, HTRA1-AS1 , and its transcript variants (ENST00000647969.1) within the ARMS2 locus. HTRA1-AS1 overlaps ARMS2 and is transcribed in the antisense orientation. It is predominantly expressed in rod photoreceptors, Müller glia and Choroid/RPE, and its retinal expression was significantly reduced in AMD compared with controls (43 AMD donors vs. 44 controls, p = 0.007). By contrast, HTRA1 mRNA showed no significant difference (p = 0.121). Furthermore, ENST00000647969.1, HTRA1-AS1 and ARMS2 expression increased dramatically, up to 101-fold, 8-fold and 75-fold, respectively, in induced pluripotent stem cells (iPSC)-derived RPE cells following cigarette smoke extract (CSE)-induced oxidative stress but showed no significant change after paraquat treatment.

CONCLUSION: These findings suggest that HTRA1-AS1 , a dysregulated lncRNA within the ARMS2 locus, may act as a non-coding element contributing to transcriptional mis-regulation underlying AMD pathogenesis.},
}

@article {pmid41282676,
year = {2025},
author = {Banijamali, SMA and Versek, C and Lashkari, K and Bex, P and Sridhar, S},
title = {Mobile Objective Diagnostics of Macular Degeneration using Dark-Adapted Visual Evoked Potentials.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {41282676},
abstract = {PURPOSE: Delayed Dark-Adapted vision Recovery (DAR) is a known biomarker for Age-related Macular Degeneration (AMD); however, its measurement is often cumbersome for both patients and examiners. In this study, we developed NeuroVEP, a portable, wireless, and user-friendly system designed to objectively assess Dark-Adapted Visual Evoked Potentials (DAVEP).

METHODS: NeuroVEP consists of a headset with a smartphone that delivers controlled photo-bleach and monocular pattern reversal stimuli while utilizing custom electroencephalography (EEG) electrodes and electronics to measure DAVEP. The system allows for separate analysis of the near peripheral and macular visual field of each eye, completing the test in a comfortable, single-session format (<25 minutes) without requiring subjective patient feedback.The NeuroVEP test protocol included: (i) Mesopic luminance pattern reversal VEP for macular and peripheral regions (5 mins), (ii) Full-field photopic pattern reversal VEP (2.5 mins), (iii) Scotopic luminance DAVEP recovery post photo-bleach (up to 15 mins), measured simultaneously from both eyes.The data were analyzed for 66 participants, divided into four cohorts: (A) Age-matched healthy controls with no ophthalmic pathologies (n=10), (B) Early-stage AMD (AREDS1) (n=19), (C) Intermediate-stage AMD (AREDS3) (n=18), (D) Advanced-stage AMD (AREDS4/5) (n=19).Advanced signal processing and machine learning methodologies were applied to filter and process the VEP responses from the DAR segment of the experiment. 13 discriminating features were extracted from the processed signals and classified for each participant using a Bayesian statistical framework and Gaussian Mixture Model (GMM).

RESULTS: The algorithm demonstrated: 86% accuracy in early-stage AMD detection (Healthy vs. Early AMD) (Sensitivity: 97%, Specificity: 65%, AUC-ROC: 0.81 and AUC-PR: 0.92) and 93% accuracy in overall AMD detection (Healthy vs. All AMD stages) (Sensitivity: 98%, Specificity: 65%, AUC-ROC: 0.82 and AUC-PR: 0.97).

CONCLUSIONS: We successfully developed a portable, objective user-friendly VEP system and an advanced Bayesian-GMM statistical analysis framework capable of identifying DAR deficits in AMD patients. This novel technology shows high potential for early AMD detection and could serve as a non-invasive, objective diagnostic tool for AMD screening in clinical and remote settings.},
}

@article {pmid41282061,
year = {2025},
author = {Lizińczyk, AM and Pankiewicz, JE and Cullina, WL and Franco, LA and Sullivan, PM and Sadowski, MJ},
title = {APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-7820890/v1},
pmid = {41282061},
issn = {2693-5015},
abstract = {APOE polymorphism affects the risk of occurrence and the rate of progression in several neurodegenerative diseases including Alzheimer's disease, primary tauopathies, α-synucleinopathy, and age-related macular degeneration, but its role in prionoses remains unestablished. Using APOE targeted replacement (TR) mice, we investigated how APOE genotype affects key neurodegenerative mechanisms involved in prion pathology. Male and female ε2/ε2 , ε3/ε3 , and ε4/ε4 APOE -TR mice were inoculated with 22L mouse-adapted scrapie strain or normal brain homogenate and monitored with behavioral testing from 10-week post inoculation (wpi.) onward. Mice were euthanized at 23 wpi. when all prion-infected animals were symptomatic, and their brains were analyzed for multiple neuropathological, biochemical, and transcriptomic metrics. ε4/ε4 22L mice featured the shortest disease latency time, the worst neurological score, and the highest load of spongiform lesions. ε2/ε2 22L mice performed significantly better than ε4/ε4 22L mice but significantly worse than ε3/ε3 22L animals. Numerous aspects of PrP proteinopathy were exacerbated in the presence of the ε4 allele including increased PrP [Sc] accumulation, reduced PrP solubility, and increased PrP oligomerization. These metrics were comparable between ε2/ε2 22L and ε3/ε3 22L mice. Prion pathology significantly increased brain apolipoprotein (apo) E levels, with the greatest increase in ε4/ε4 22L mice. All apoE isoforms formed complexes with conformationally altered PrP, but this interaction was the strongest in ε4/ε4 22L mice. ε4/ε4 22L mice had the highest load of reactive microglia and astrocytes and upregulation of transcriptomic markers typical of neurodegenerative microglia and astrocytes, followed by ε2/ε2 22L , with ε3/ε3 22L having the lowest. Thus, APOE polymorphism differentially regulates the progression of prion pathology attributable to two ε4 -affected mechanisms: increased conversion and accumulation of PrP [Sc] and worsened prion-associated neuroinflammation. Though less severely than ε4 , the ε2 allele also increased the inflammatory response, rendering disease outcome worse relative to the ε3 allele. Our findings suggest both ε4 and ε2 alleles are disadvantageous determinants in prion pathology.},
}

@article {pmid41281747,
year = {2025},
author = {Yang, B and Yang, K and Chen, Y and Xi, R and Han, J and Li, S and Chen, J and Wu, Y},
title = {Activation of GSDME by all-trans-retinal increases sensitivity to photoreceptor ferroptosis.},
journal = {International journal of biological sciences},
volume = {21},
number = {15},
pages = {7029-7042},
pmid = {41281747},
issn = {1449-2288},
mesh = {Animals ; *Ferroptosis/physiology/drug effects/genetics ; Mice ; Mice, Knockout ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; *Photoreceptor Cells, Vertebrate/metabolism ; *Retinaldehyde/metabolism/pharmacology ; Mice, Inbred C57BL ; Lipid Peroxidation ; Mitochondria/metabolism ; Retinal Degeneration/metabolism ; Macular Degeneration/metabolism ; ATP-Binding Cassette Transporters ; },
abstract = {Impaired clearance of all-trans-retinal (atRAL) due to visual cycle dysfunction contributes to photoreceptor atrophy, a key pathological hallmark of Stargardt disease type 1 (STGD1) and dry age-related macular degeneration (AMD). Prior studies have shown that light-induced atRAL accumulation promotes ferroptosis and activates gasdermin E (GSDME) in retinal photoreceptors of Abca4[-/-]Rdh8[-/-] mice, a model for STGD1 and dry AMD that exhibits visual cycle disorders. However, the role of GSDME in photoreceptor ferroptosis remains unclear. In this study, we revealed that GSDME activation by atRAL triggered photoreceptor ferroptosis and retinal atrophy via mitochondrial damage and oxidative stress. Knocking out GSDME significantly attenuated light-induced photoreceptor ferroptosis and retinal degeneration in Abca4[-/-]Rdh8[-/-] mice. Moreover, deleting the Gsdme gene in photoreceptor cells prevented atRAL-induced ferroptosis by inhibiting mitochondrial reactive oxygen species (mitoROS) production, iron overload, and lipid peroxidation. Notably, treatment with the mitoROS scavenger MitoTEMPO mitigated ferroptosis in atRAL-loaded photoreceptor cells and dramatically relieved photoreceptor ferroptosis and retinal degeneration in light-exposed Abca4[-/-]Rdh8[-/-] mice. We found that both GSDME elimination and MitoTEMPO treatment repressed atRAL-induced photoreceptor ferroptosis and retinal atrophy by inactivating the mitoROS-induced oxidative stress. In conclusion, GSDME-mediated photoreceptor ferroptosis is crucial for inducing structural and functional damage of the retina in retinopathies caused by atRAL accumulation, thereby providing new therapeutic insights for the prevention and treatment of STGD1 and dry AMD.},
}

Animals
*Ferroptosis/physiology/drug effects/genetics
Mice
Mice, Knockout
Oxidative Stress
Reactive Oxygen Species/metabolism
*Photoreceptor Cells, Vertebrate/metabolism
*Retinaldehyde/metabolism/pharmacology
Mice, Inbred C57BL
Lipid Peroxidation
Mitochondria/metabolism
Retinal Degeneration/metabolism
Macular Degeneration/metabolism
ATP-Binding Cassette Transporters

@article {pmid41280070,
year = {2025},
author = {Shin, K and Brown, W and Tian, Y and Gopinath, T and Bobkov, AA and Marinelli, F and Marassi, FM},
title = {Structural basis for lipid binding by the blood protein vitronectin, a component of HDL.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.11.01.685992},
pmid = {41280070},
issn = {2692-8205},
abstract = {Vitronectin (Vn) is a multifunctional blood glycoprotein involved in cell adhesion and migration, blood coagulation, and inflammation. It is a component of the high-density lipoprotein (HDL) proteome, and often found associated with the calcified, lipid-rich, protein deposits that are a hallmark of age-related macular degeneration, Alzheimer's disease, atherosclerosis and other aging-related diseases. Here we explored the molecular basis for lipid binding by Vn using isothermal titration calorimetry (ITC), nuclear magnetic resonance (NMR) and all-atom molecular dynamics (MD) simulations. The data reveal a hydrophobic groove on the surface of the hemopexin-like (HX) domain of Vn, that is capable of binding phosphatidylcholine (PC). Conformational landscape analyses of multiple, independent MD simulations identify key structural motifs and intermolecular contacts mediating the association of Vn with PC, and show that lipid binding is guided by interactions with positively charged and hydrophobic residues that organize the lipids in a tail-to-tail bilayer-like arrangement within the groove. Collectively, the data establish a comprehensive structural model for Vn association with HDL and provide mechanistic insight into its accumulation within lipid-rich deposits characteristic of age-related pathologies.},
}

@article {pmid41279388,
year = {2025},
author = {Maniglia, M and Vice, J and Maxwell, E and Visscher, KM and Seitz, AR},
title = {Examining oculomotor behavior in central vision loss with a gaze-contingent display.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41279388},
issn = {2692-8205},
support = {R21 EY033623/EY/NEI NIH HHS/United States ; },
abstract = {Patients with central vision loss due to macular degeneration (MD) must rely on their peripheral vision for tasks normally performed by the fovea. Many patients develop a preferred retinal locus (PRL), an eccentric retinal location used as a substitute for the damaged fovea in tasks such as face recognition, navigation, and reading. However, the mechanisms underlying PRL development remain elusive, and no single hypothesis fully explains its characteristics. Investigations into PRL development are hindered by oculomotor assessments, which often focus on fixation ability while neglecting other eye movement characteristics and potentially conflating different behaviors over time. In previous work, we introduced a series of oculomotor metrics in cases of simulated central vision loss, demonstrating that complex profiles of eye movement behavior can be extracted from a simple visual task. Here we present longitudinal data from 10 patients with MD as evidence of the feasibility of using these metrics to characterize different profiles of eye movements following central vision loss. Consistent with findings in healthy individuals using artificial scotoma, the metrics reveal substantial individual differences in behavior, both at baseline and after visual training. Overall, patients exhibit significantly higher saccadic re-referencing than controls, despite larger inter-individual differences. These metrics provide a detailed evaluation of oculomotor behavior in patients with central vision loss and offer a valuable tool for assessing progress in training protocols.},
}

@article {pmid41279129,
year = {2025},
author = {Zhang, PW and Liu, S and Li, W and Fan, L and Li, S and Wan, ZH and Berlinicke, CA and Merbs, SL and Zack, DJ},
title = {Identification and functional characterization of an AMD associated c-ABL binding SNP streak within the ARMS2 gene promoter region.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.1101/2025.10.27.684937},
pmid = {41279129},
issn = {2692-8205},
abstract = {BACKGROUND: Large-scale genome-wide association studies (GWAS) have identified the human 10q26 locus as a major genetic risk factor for age-related macular degeneration (AMD). The AMD-associated interval has been refined to a 5,196 bp segment flanking the ARMS2-HTRA1 region, excluding HTRA1 and the ARMS2 3' indel (443del54ins) variant by risk haplotype analysis. Although the missense SNP rs10490924 has been proposed as a functional variant, its role in AMD remains controversial, and the causative variants and underlying mechanisms within this region remain unresolved.

METHODS: An unbiased bioinformatic screen identified a 5-SNP block within the 5,196 bp interval that potentially alters c-ABL protein binding. Protein-DNA interactions were validated using electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assays. Genetic association with AMD (dry and wet subtypes) was assessed in patient cohorts using blood genomic DNA. The regulatory effect of the 5-SNP block was further examined using luciferase reporter assays.

FINDINGS: We identified a 5-SNP block located ∼556 bp upstream of the ARMS2 start codon, representing a cluster of predicted c-ABL tyrosine kinase binding sites. This block, in complete linkage disequilibrium with rs10490924 (A69S), showed a strong association with both wet and dry AMD (136 controls, 179 dry AMD, 251 wet AMD). EMSA and ChIP confirmed direct c-ABL binding, while luciferase reporter assays demonstrated reduced transcriptional activity mediated by the 5-SNP block in the presence of c-ABL.

INTERPRETATION: Our results suggest that the c-ABL-responsive 5-SNP regulatory streak in the ARMS2 promoter region act as functional non-coding elements that may contribute to AMD pathogenesis through altered transcriptional regulation.},
}

@article {pmid41278837,
year = {2025},
author = {Oshima, Y and Hussey, KA and Hagen, J and Smit-McBride, Z and Moorthy, M and Matsubara, JA and Flajnik, M and Johnston, RJ and Vogel, BE},
title = {Complement Factor H and its C. elegans homolog regulate IFT52/OSM-6 and CNG channel localization in sensory neurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41278837},
issn = {2692-8205},
support = {P30 EY012576/EY/NEI NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Current disease models propose AMD pathogenesis is a consequence of cytolytic damage and tissue inflammation that result from defective repression of alternative complement pathway activity by complement factor H (CFH). However, recent studies demonstrate functions for CFH that are outside of its established role in the alternative complement pathway, suggesting that novel CFH-mediated mechanisms may influence AMD initiation and progression. Our previous demonstration that CFH and its nematode homolog, CFH-1, modulate inversin/NPHP-2 accumulation in vertebrate photoreceptor and C. elegans sensory neuron cilia during aging suggests that AMD patients with CFH loss-of-function mutations have cilia defects that may contribute to photoreceptor dysfunction. Here, we investigate the consequences of CFH and CFH-1 loss-of-function mutations on the dynamics and localization of intraflagellar transport (IFT) train and visual cycle components in these cells. In C. elegans sensory neurons, IFTB1 components IFT52/OSM-6 and IFT88/OSM-5 are transported at similar rates in WT animals but IFT52/OSM-6 transport slows significantly in cfh-1 mutant animals while IFT88/OSM-5 is unaffected. Defective localization of IFT52/OSM-6 in photoreceptors of CFH knockout mice and in human photoreceptors from AMD high-risk CFH Y402H homozygotes, suggest an evolutionarily conserved role for CFH in promoting IFT52/OSM-6 transport and localization in sensory neuron cilia. In addition, distribution of CNG channel subunits in C. elegans cfh-1 mutant sensory neurons and CFH Y402H high-risk human photoreceptors are distinct from their WT and Y402 low-risk counterparts. Together, the data indicate previously unappreciated functions for CFH in IFT train organization and cilia protein localization and suggest a novel mechanism for photoreceptor segment thinning, an early AMD biomarker that has been linked to CFH high-risk variants.},
}

@article {pmid41278702,
year = {2025},
author = {Oshima, Y and Nagidi, Y and Moorthy, ME and Heier, J and Matsubara, JA and Hardin, J and Flajnik, M and Vogel, BE},
title = {TEP-1, a glial thioester protein is required for cilia organization and intraflagellar transport in ensheathed sensory neurons.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {41278702},
issn = {2692-8205},
support = {P40 OD010440/OD/NIH HHS/United States ; R01 EY032868/EY/NEI NIH HHS/United States ; },
abstract = {Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, is characterized by progressive degeneration of retinal photoreceptors. Traditional disease models suggest that defective repression of thioester protein C3 activity by complement factor H (CFH) is a major contributor to pathogenesis in AMD and a related disease, early-onset drusen maculopathy (EODM). Our previous study identified novel functions for human CFH and C. elegans CFH-1 in the maintenance of inversin compartment integrity in photoreceptors and mechanosensory neurons, indicating that CFH has a novel, evolutionarily conserved role in cilia compartment organization that is distinct from its established function in alternative complement pathway regulation. Here, we investigate the C. elegans thioester protein TEP-1, an ancestral relative of C3 and other members of the AMCOM family (C4, C5, CD109, and alpha-2-macroglobulin). TEP-1 localizes to select glial cell surfaces and regulates inversin compartment organization and intraflagellar transport (IFT) within the cilia of ensheathed sensory neurons. In addition to revealing a novel role for an AMCOM family member in sensory neuron structure and protein transport, the localization of C3 and CFH on human photoreceptors provides support for non-canonical models of AMD and EODM pathogenesis in which defects in cilia structure and protein transport contribute directly to the progressive photoreceptor dysfunction that characterizes these diseases.},
}

@article {pmid41277047,
year = {2025},
author = {Choe, S and Ye, J and Zhang, T and Gao, J},
title = {Advanced Drug Delivery Systems for Age-Related Macular Degeneration Treatment: Latest Trends and Future Prospects.},
journal = {Advanced healthcare materials},
volume = {},
number = {},
pages = {e03757},
doi = {10.1002/adhm.202503757},
pmid = {41277047},
issn = {2192-2659},
support = {W2442037//National Natural Science Foundation of China/ ; 2023GSP006851//Chinese Government Scholarship/ ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. While wet AMD is primarily characterized by choroidal neovascularization, dry AMD is characterized by dysfunction of the retinal pigment epithelium. One of the key challenges in AMD treatment is achieving efficient drug delivery to the posterior segment, a task complicated by the anatomical and physiological barriers, such as rapid clearance from the vitreous. Current therapeutic approaches, mainly constituted by frequent intravitreal injections of anti-vascular endothelial growth factor agents for wet AMD, place a heavy burden on patients, leading to complications such as retinal detachment and endophthalmitis. This review highlights recently developed drug delivery systems designed to overcome these challenges and the potential of these systems to transform AMD management. These systems include hydrogels, nanocarriers, and biologically derived vesicles, which enable sustained, localized drug release and improved targeting. Additionally, device-based delivery systems such as microneedles, ultrasound-mediated systems, magnetically guided systems, 3D bioprinting, and implantable sustained-release devices are explored for their potential to reduce injection frequency and improve therapeutic outcomes. Lastly, it outlines future efforts needed to accelerate the clinical adoption of these innovative therapies, with a focus on patient safety, efficacy, and quality of life in AMD treatment.},
}

@article {pmid41276957,
year = {2025},
author = {Yang, CC and Weng, CC and Chou, YB and Huang, YM and Lin, TC and Chen, SJ and Hwang, DK},
title = {Early anatomical outcomes of faricimab vs. aflibercept 2 mg in treatment-naïve neovascular AMD and PCV: A head-to-head comparative study in Taiwan.},
journal = {Journal of the Chinese Medical Association : JCMA},
volume = {},
number = {},
pages = {},
doi = {10.1097/JCMA.0000000000001320},
pmid = {41276957},
issn = {1728-7731},
abstract = {BACKGROUND: While clinical trials have established the non-inferiority of faricimab compared to aflibercept regarding 1-year visual acuity, real-world evidence directly comparing their early effects on anatomical changes remains limited. This study aimed to compare the early effects of these treatments in treatment-naïve Asian patients with neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV).

METHODS: This retrospective study included treatment-naive nAMD patients who received three monthly intravitreal injections of 6.0 mg/0.05 mL faricimab or 2.0 mg/0.05 mL aflibercept. Best-corrected visual acuity (BCVA), central macular thickness (CMT), subfoveal choroidal thickness (SFCT), pigment epithelial detachment (PED), subretinal fluid (SRF), intraretinal fluid (IRF), hyperreflective foci (HRF), and subretinal hyperreflective material (SHRM) were assessed monthly for 4 months.

RESULTS: A total of 76 eyes of 76 patients (38 per group) were enrolled in this study. Baseline characteristics were comparable between the two groups, and there were no significant differences in BCVA, CMT, SFCT, SRF and IRF at 4 months (p > 0.05). However, the faricimab group had significant improvements in BCVA at months 2, 3, and 4 (p < 0.05), while this was not seen in the aflibercept group. The decrease in mean logarithm of the minimum angle of resolution (logMAR) was from 0.78 ± 0.47 to 0.66 ± 0.65 in the faricimab group compared to 0.78 ± 0.41 to 0.72 ± 0.60 in the aflibercept group (p = 0.348) at 4 months. Moreover, significantly fewer faricimab-treated patients had PED (67.6% vs. 91.9%, p = 0.016), SHRM (32.4% vs. 59.5%, p = 0.022), and HRF (52.9% vs. 89.2%, p = 0.001) at 4 months.

CONCLUSION: Faricimab and aflibercept demonstrated comparable effects on BCVA, CMT, and SFCT. However, faricimab was associated with better early control of PED, SHRM, and HRF. Further prospective trials are needed to validate our findings.},
}

@article {pmid41275318,
year = {2025},
author = {Lim, J and Cho, H and Ramkumar, H and Adrean, SD},
title = {Neovascular age-related macular degeneration complicated by large submacular hemorrhage managed with faricimab monotherapy.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00771-5},
pmid = {41275318},
issn = {2056-9920},
}

@article {pmid41273407,
year = {2025},
author = {Ferreira, AM and Vilares-Morgado, R and Martins, L and Marques-Couto, P and Rocha-Sousa, A and Carneiro, Â and Falcão, M},
title = {Non-exudative macular neovascularization: a 3-year follow-up study assessing the progression for exudative or atrophic stages.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41273407},
issn = {1435-702X},
abstract = {INTRODUCTION: Non-exudative macular neovascularization (NE-MNV) has been linked to smaller areas of geographic atrophy (GA), suggesting it may slow the progression of complete retinal pigment epithelium and outer retinal atrophy (cRORA). This study aims to determine whether NE-MNV affects the prevalence and progression to later stages of age-related macular degeneration (AMD) over 3 years in the fellow eyes of patients with unilateral exudative AMD.

METHODS: Observational study including 61 patients with unilateral exudative AMD assessing 3-year cRORA progression and exudative conversion in the fellow eye. Patients were grouped based on the presence (NE-MNV) or absence of NE-MNV (no NE-MNV). The prevalence and progression of tomographic cRORA, GA on fundus autofluorescence (FAF) and exudative conversion rates were compared.

RESULTS: Sixty-one patients were included in our cohort. The prevalence of NE-MNV was 24.6%. We identified a 36.3% bilateral exudative conversion rate (n = 4) in the NE-MNV group and a 15.2% conversion rate in the eyes without NE-MNV (n = 7) at 3 years (p = 0.036). There were no significant differences in cRORA or FAF GA prevalence between groups (2/15 (13.3%) with NE-MNV vs. 11/35 (31.4%) without NE-MNV, p = 0.410). Eyes with NE-MNV presented a significantly smaller cRORA greatest linear diameter (GLD) than eyes without NE-MNV (1342.3 ± 1260 vs. 2897 ± 1925.3, p = 0.023), and a smaller FAF GA area (4.5 ± 3.7 vs. 11.9 ± 10.6 mm2, p = 0.042). The presence of reticular pseudodrusen and hypertransmission defects were significantly associated with the GA phenotype (p = 0.002 and p < 0.001, respectively) while the identification of concurrent large drusen was significantly associated with the presence of MNV, both exudative and non-exudative (p = 0.023). The increase in OCTA NE-MNV area and the presence of anastomosis and loops pattern were associated with exudative conversion (p = 0.046 and p = 0.032, respectively).

CONCLUSION: The presence of NE-MNV was associated with smaller cRORA GLD and FAF GA area, corroborating that NE-MNV may prevent the progression of cRORA. One third of the eyes with NE-MNV converted to exudative AMD over 3-years. Reticular pseudodrusen, hypertransmission defects and concurrent large drusen were significant OCT biomarkers for late stages AMD. Extended monitoring is required to confirm these results at long term.},
}

@article {pmid41272236,
year = {2025},
author = {Pidishetty, D and Damera, SK and Murugavel, M and Susaimanickam, PJ and Chittajallu, SNSH and Kushawah, G and Sarkar, P and Bharadwaj, SR and Mishra, R and Mariappan, I},
title = {Loss of retinal stem cell reserve and lipofuscin accumulation accelerates cone-rod degeneration and replicates Stargardt disease in abca4b null zebrafish.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-025-28951-1},
pmid = {41272236},
issn = {2045-2322},
abstract = {Mutations in ABCA4 gene causes Stargardt macular degeneration, which manifests with toxic lipofuscin deposits in the outer retina, gradual atrophy of RPE cells, followed by photoreceptor cell loss. The cone-enriched retina, with macula-like 'area-temporalis' of zebrafish are better models than rodents for studying human macular dystrophies. Here, we generated abca4b knockout zebrafish model using CRISPR/Cas9 editing and evaluated the early and late-stage retinal changes. In adult abca4b[-/-] mutants, the RPE cells exhibited hyperpigmentation, altered retinomotor behaviour and lipofuscin accumulation, but they remained viable. However, the photoreceptors underwent progressive degeneration, with a sequential loss of blue and UV cones, followed by red and green cones and finally the rod cells. This triggered the chronic activation and early depletion of retinal stem cells at the ciliary marginal zone of mutants and resulted in accelerated outer-retinal degeneration and severe visual defects, despite them retaining the Müller glia-dependant retinal repair potential.},
}

@article {pmid41271910,
year = {2025},
author = {Tabuchi, H and Nagasato, D and Tanabe, M and Murata, K and Ishitobi, N and Kato, D and Kazunori, A},
title = {Evaluation of deep learning-based retinal pigment epithelium segmentation for a widely used optical coherence tomography device.},
journal = {Scientific reports},
volume = {15},
number = {1},
pages = {41310},
pmid = {41271910},
issn = {2045-2322},
mesh = {Humans ; *Tomography, Optical Coherence/methods/instrumentation ; *Retinal Pigment Epithelium/diagnostic imaging/pathology ; *Deep Learning ; Algorithms ; Aged ; Macular Degeneration/diagnostic imaging ; Male ; Female ; Diabetic Retinopathy/diagnostic imaging ; Middle Aged ; *Image Processing, Computer-Assisted/methods ; },
abstract = {To develop our proposed technology method to improve retinal pigment epithelium (RPE) detection in optical coherence tomography (OCT) images and compare its efficacy with Topcon's automated segmentation algorithm across multiple retinal diseases and healthy eyes. OCT images from 88 patients with age-related macular degeneration (AMD) were used for our proposed technology model training and validation. For testing with separate images were obtained from patients with AMD (100), diabetic retinopathy (DR; 50), epiretinal membrane (ERM; 50), branch retinal vein occlusion (BRVO; 50), and healthy eyes (50). The proposed technology was used to identify RPE in OCT images using the Pyramid Scene Parsing Network on top of ResNet-50. The accuracy of the proposed technology method in RPE detection was measured using the mean absolute error (MAE) and compared with Topcon's automated segmentation algorithm for each retinal condition. As compared with Topcon's automated segmentation algorithm, the proposed technology showed significantly better MAEs across all conditions: AMD (2.18 vs. 4.79), DR (1.69 vs. 3.17), ERM (1.50 vs. 2.67), BRVO (1.86 vs. 2.98), and healthy eyes (1.59 vs. 2.28). Notably, the proposed technology's superiority was most evident in the AMD group. The proposed technology method outperformed Topcon's automated segmentation algorithm in accurately visualizing RPE in OCT images across all tested conditions, especially in AMD. Our results indicate the proposed technology's potential to elevate the RPE segmentation which can lead to enhancing ophthalmology care by providing more accurate OCT imaging analyses.},
}

Humans
*Tomography, Optical Coherence/methods/instrumentation
*Retinal Pigment Epithelium/diagnostic imaging/pathology
*Deep Learning
Algorithms
Aged
Macular Degeneration/diagnostic imaging
Male
Female
Diabetic Retinopathy/diagnostic imaging
Middle Aged
*Image Processing, Computer-Assisted/methods

@article {pmid41270813,
year = {2025},
author = {Jiang, L and Xu, Z and Ma, J and Cai, W and Lin, R and Hu, C and Luo, Y and Liang, F and Wu, Y and Yu, J},
title = {siRASA1 in vascular endothelial cells alleviates subretinal fibrosis through inhibiting macrophage-myofibroblast transdifferentiation via SHH signaling pathway.},
journal = {Cellular signalling},
volume = {138},
number = {},
pages = {112261},
doi = {10.1016/j.cellsig.2025.112261},
pmid = {41270813},
issn = {1873-3913},
abstract = {Subretinal fibrosis (SRF) is a vision-threatening complication of neovascular age-related macular degeneration (nAMD) driven by angiogenesis, inflammation, and collagen deposition，which is refractory to current anti-VEGF treatments. This study investigates the role of RASA1 in promoting SRF through Sonic Hedgehog (SHH) signaling. We found that VEGF stimulation upregulates RASA1 in human umbilical vein endothelial cells (HUVECs), potentiating the secretion of SHH. Secreted SHH then activates the SHH-SMO/PTCH1-GLI1 axis in macrophages, driving their transdifferentiation into myofibroblasts and promoting fibrogenesis. Furthermore, a positive feedback loop was identified: macrophage-derived EFNB2 activated EphB4-RASA1 in HUVECs, exacerbating fibrosis. To therapeutically disrupt this circuit, we engineered a multifunctional nanoparticle system, MGPDA@Eylea/siRASA1, for the co-delivery of siRASA1 and the anti-VEGF drug Eylea. This nanotherapeutic demonstrated excellent biocompatibility and effectively attenuated the fibrotic cascade by suppressing RASA1 expression, inhibiting SHH signaling, and mitigating macrophage-to-myofibroblast transition (MMT), thereby delaying SRF progression. Our work unveils a previously unrecognized intercellular circuit driving fibrosis and presents a promising nanomedicine-based strategy for managing fibrotic complications in nAMD.},
}

@article {pmid41270236,
year = {2025},
author = {Shi, N and Li, J and Shang, M and Zhang, W and Xu, K and Li, Y and Liang, L},
title = {Detection and Management of Geographic Atrophy Secondary to Age-Related Macular Degeneration Using Noninvasive Retinal Images and Artificial Intelligence: Systematic Review.},
journal = {Journal of medical Internet research},
volume = {27},
number = {},
pages = {e81328},
pmid = {41270236},
issn = {1438-8871},
mesh = {Humans ; *Artificial Intelligence ; Deep Learning ; *Geographic Atrophy/diagnostic imaging/etiology/diagnosis/therapy ; *Macular Degeneration/complications/diagnostic imaging ; *Retina/diagnostic imaging ; Tomography, Optical Coherence ; },
abstract = {BACKGROUND: Geographic atrophy (GA), the endpoint of dry age-related macular degeneration (AMD), is irreversible. The recent approval by the Food and Drug Administration of a complement component 3 inhibitor marks a significant breakthrough, highlighting the critical importance of early detection and management of GA. Consequently, there is an urgent and unmet need for efficient, accurate, and accessible methods to identify and monitor GA. Artificial intelligence (AI), particularly deep learning (DL), applied to noninvasive retinal imaging, offers a promising solution for automating and enhancing GA management.

OBJECTIVE: This systematic review aimed to assess the performance of AI using noninvasive imaging modalities and compare it with clinical expert assessment as the ground truth.

METHODS: Two consecutive searches were conducted on PubMed, Embase, Web of Science, Scopus, Cochrane Library, and CINAHL. The last search was performed on October 5, 2025. Studies using AI for GA secondary to dry AMD via noninvasive retinal imaging were included. Two authors worked in pairs to extract the study characteristics independently. A third author adjudicated disagreements. Quality Assessment of Diagnostic Accuracy Studies-AI and Prediction Model Risk of Bias Assessment Tool (PROBAST) were applied to evaluate the risk of bias and application.

RESULTS: Of the 803 records initially identified, 176 were found through an updated search. Subsequently, 200 papers were assessed in full text, of which 41 were included in the final analysis, 10 for GA detection, 20 for GA assessment and progression, and 11 for GA lesion prediction. The reviewed studies collectively involved at least 24,592 participants (detection: n=7132, assessment and progression: n=14,064, and prediction: n=6706), with a wide age range of 50 to 94 years. The studies spanned a diverse array of countries, including the United States, the United Kingdom, China, Austria, Australia, France, Israel, Italy, Switzerland, and Germany, as well as a multicenter study encompassing 7 European nations. The studies used a variety of imaging modalities to assess GA, including color fundus photography, fundus autofluorescence, near-infrared reflectance, spectral domain-optical coherence tomography (OCT), swept-source (SS)-OCT, and 3D-OCT. DL algorithms (eg, U-Net, ResNet50, EfficientNetB4, Xception, Inception v3, and PSC-UNet) consistently showed remarkable performance in GA detection and management tasks, with several studies achieving performance comparable to clinical experts.

CONCLUSIONS: AI, particularly DL-based algorithms, holds considerable promise for the detection and management of GA secondary to dry AMD with performance comparable to ophthalmologists. This review innovatively consolidates evidence across GA management-from initial detection to progression prediction-using diverse noninvasive imaging. It has strong potential to augment clinical decision-making. However, to realize this potential in real-world settings, future research is needed to robustly enhance reporting specifications, ensure data diversity across populations and devices, and implement rigorous external validation in prospective, multicenter studies.},
}

Humans
*Artificial Intelligence
Deep Learning
*Geographic Atrophy/diagnostic imaging/etiology/diagnosis/therapy
*Macular Degeneration/complications/diagnostic imaging
*Retina/diagnostic imaging
Tomography, Optical Coherence