@article {pmid41454061,
year = {2025},
author = {Guo, S and Liu, R and Liu, Y and Liu, F},
title = {Comment on "Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration".},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41454061},
issn = {1476-5454},
}

@article {pmid41453674,
year = {2025},
author = {Palakkan, AA and Kumar, GS},
title = {Retinal Organoids in Age-Related Macular Degeneration: Promise, Pitfalls, and Progress.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110831},
doi = {10.1016/j.exer.2025.110831},
pmid = {41453674},
issn = {1096-0007},
abstract = {Recent advancements in organoid technology have revolutionized our understanding of organ development and disease modelling. However, despite significant progress, retinal organoids continue to face several limitations, including imperfect architecture, incomplete maturation, limited functional integration, and lack of vascularization. These challenges hinder their potential as accurate models of human retinal biology and disease. In this review, we examine the currently available models of age-related macular degeneration, evaluate the potential of retinal organoids, and discuss their respective advantages and limitations. We also explore strategies to overcome the existing challenges in retinal organoid systems, drawing parallels from progress made in other organoid fields, where similar limitations have been addressed. Implementing these strategies may enhance the structural and functional fidelity of retinal organoids, thereby improving their utility in modelling retinal disorders and advancing regenerative medicine.},
}

@article {pmid41453515,
year = {2025},
author = {Myers, WK and Heath, G and Rohrer, B},
title = {Rate of Age-Related Macular Degeneration in Patients Prescribed Glucagon-Like Peptide-1 Receptor Agonists or Other Weight Loss Therapy.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.12.016},
pmid = {41453515},
issn = {2468-6530},
abstract = {PURPOSE: To compare the hazard of age-related macular degeneration (AMD) among non-diabetic, weight loss-eligible adults prescribed glucagon-like peptide-1 receptor agonists (GLP-1 RAs; semaglutide or liraglutide) versus other weight loss pharmacotherapies (OWL; phentermine, orlistat, setmelanotide, phentermine-topiramate, or bupropion-naltrexone).

DESIGN: Retrospective cohort study.

PARTICIPANTS: Adults ≥ 50 years without diabetes meeting criteria for weight loss pharmacotherapy and prescribed GLP-1 RAs or OWL medications. Before matching, 60 336 patients were included in the GLP-1 RA group and 21 609 in the OWL cohort; after matching, 20 959 patients remained in each cohort.

METHODS: Cohorts were constructed using deidentified data from the TriNetX Research Network (June 2021 - October 2025). Non-diabetic status was defined as absence of diabetes mellitus diagnosis, hemoglobin A1c ≥ 6.5%, or metformin or insulin use. Patients met criteria for weight loss pharmacotherapy with documentation of an obesity diagnosis, BMI ≥ 30 kg/m[2], or BMI ≥ 27 kg/m[2] with dyslipidemia or hypertension, recorded within 1 year before initiation. Inclusion required ≥ 2 prescriptions for a single study medication at least 6 months apart. Patients with recorded medication cross-exposure or outcome diagnoses prior to index were excluded. Cohorts were matched for demographics, established AMD risk factors, covariates influencing treatment allocation, access to ophthalmological care, and proxies for social determinants of health using 1:1 propensity score matching. Outcomes were assessed using Cox proportional hazards models.

MAIN OUTCOME MEASURES: Hazard ratios of nonexudative AMD, exudative AMD, and any AMD (exudative, nonexudative, or unspecified). Changes in BMI and hemoglobin A1c were analyzed to contextualize findings.

RESULTS: Compared with other weight loss pharmacotherapies, GLP-1 RAs were associated with a lower hazard of nonexudative AMD (HR, 0.47; 95% CI, 0.28-0.78) and any AMD (HR, 0.61; 95% CI, 0.43-0.85), with no difference for exudative AMD (HR, 0.63; 95% CI, 0.30-1.32). BMI and hemoglobin A1c were similar over follow-up.

CONCLUSIONS: Among non-diabetic adults ≥ 50 years old eligible for weight loss pharmacotherapy, prescriptions for GLP-1 RAs were associated with a lower incidence of nonexudative and any (nonexudative, exudative, or unspecified) AMD diagnoses compared with other weight loss medications. The difference in new exudative AMD diagnoses was not statistically significant.},
}

@article {pmid41452565,
year = {2025},
author = {Koizumi, H and Honda, S and Yasukawa, T and Kishino, G and Sekiryu, T and Schulze, A and Yamashita, T and Schmidt-Ott, U and Zhao, M and Zhang, X and Berliner, AJ and Chu, KW and Reed, K and Cheng, Y and Bhore, R and Vitti, R and Fujita, I and Leal, S and Iida, T and , },
title = {Intravitreal aflibercept 8 mg in patients from Japan with neovascular age-related macular degeneration: 48-week subgroup analysis of the PULSAR trial.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {41452565},
issn = {1613-2246},
abstract = {PURPOSE: To evaluate the 1-year efficacy and safety of aflibercept 8 mg compared with aflibercept 2 mg in a pre-specified analysis of patients from Japan with neovascular age-related macular degeneration (nAMD) included in PULSAR.

STUDY DESIGN: PULSAR (NCT04423718) was a global, phase 3, randomized, double-masked, non-inferiority study of adults with nAMD. Patients were randomized 1:1:1 to receive aflibercept 8 mg every 12 weeks (8q12), or every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups.

METHODS: This subgroup analysis of Japan and non-Japan cohorts from PULSAR evaluated changes from baseline in best-corrected visual acuity (BCVA), central subfield retinal thickness, durability and safety outcomes.

RESULTS: In the Japan subgroup, least squares (LS) mean (95% CI) changes from baseline in BCVA at week 48 were +6.5 (+0.7, +12.3), +7.9 (+5.1, +10.6), and +4.7 (-0.5, +9.9) letters for patients in the 8q12 (n = 31), 8q16 (n = 33), and 2q8 (n = 33) groups, respectively. The majority of patients in the 8q12 (82.1%) and 8q16 (93.8%) groups maintained their randomized dosing intervals through Week 48. Ocular treatment-emergent adverse events were reported in 35.5%, 30.3%, and 39.4% of patients in the Japan subgroup in 8q12, 8q16, and 2q8 groups, respectively. Similar efficacy and safety results were observed in the non-Japan subgroup.

CONCLUSION: Aflibercept 8 mg has similar efficacy and safety to aflibercept 2 mg when administered at extended dosing intervals in both the Japan and non-Japan subgroups, consistent with the overall PULSAR results.},
}

@article {pmid41451083,
year = {2025},
author = {Chen, X and Li, H and Jiao, Z and Liu, Y and Wu, Y and Qiu, X and Zou, Y and Liu, G},
title = {Association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and age-related macular degeneration: insights from two observational studies.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1724938},
pmid = {41451083},
issn = {2296-858X},
abstract = {OBJECTIVES: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is an innovative measure for assessing cardiovascular disease risk, primarily associated with lipid profiles. Lipid metabolism disorders have been reported to be associated with age-related macular degeneration (AMD), yet the relationship between NHHR and AMD has not been previously explored. This study primarily aims to investigate the potential association between NHHR and the prevalence of AMD.

METHODS: A comprehensive cross-sectional stratified survey using the National Health and Nutrition Examination Survey (NHANES) dataset of the US was conducted, including 4,017 participants aged 40 years and older, from 2005 to 2008. The NHHR was calculated as [Total Cholesterol (TC) - High-Density Lipoprotein Cholesterol (HDL-C)]/HDL-C. Data on AMD were derived from retinal photography. Logistic regression, stratified analysis, RCS curve, ROC/AUC, and subgroup interaction analysis were used to explore the relationship between NHHR and AMD. Meanwhile, patients who visited the People's Hospital Affiliated to Fujian University of Traditional Chinese Medicine (PHFT, China) between November 2021 and September 2025 were recruited retrospectively. All participants who met the study inclusion criteria were screened from the hospital-wide integrated informatics platform for clinical research. Finally, the clinical data of 96 eligible participants of PHFT were included in this study for conducting external validation analysis.

RESULTS: The cross-sectional study from NHANES included 4,017 participants, of whom 3,678 (91.56%) had no AMD and 339 (8.44%) exhibited AMD. The external validation study from PHFT consisted of 48 patients with AMD and 48 non-AMD participants. Both studies indicated that compared with the non-AMD group, the AMD group had a significantly lower NHHR (p < 0.01). In the fully adjusted Model, when NHHR was stratified into tertiles, the results showed that for each one-unit increase in NHHR, the risk of AMD in individuals in the highest tertile was reduced by 33.1 and 76.8%, respectively. The results of the RCS curve and threshold effect analyses from the two studies confirmed a negative correlation trend between the two variables (p < 0.05). The subgroup and interaction analysis, based on data from the NHANES, shows consistent associations between NHHR and AMD across various subgroups.

CONCLUSION: Our preliminary research indicates that NHHR might be a reliable independent indicator of the risk of developing AMD. In the future, large-scale sample studies and more prospective research are still needed to confirm our findings.},
}

@article {pmid41450867,
year = {2026},
author = {Mukherjee, S and Nagarkar, A and Prasad, M and Agron, E and Weber, C and Chew, EY and De Silva, T},
title = {A Datasheet for Age-Related Eye Disease Study 2 on the Database of Genotypes and Phenotypes.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {100953},
pmid = {41450867},
issn = {2666-9145},
abstract = {OBJECTIVE: To provide a comprehensive summary of the controlled-access Age-Related Eye Disease Study 2 (AREDS2) data elements, encompassing phenotypic, imaging, dietary, genetic, and ancillary data.

DESIGN: Dataset description of a multicenter, phase III, randomized clinical trial evaluating lutein + zeaxanthin, ω-3, or both long-chain polyunsaturated fatty acid supplementation in intermediate age-related macular degeneration (AMD). Secondary randomization was offered to all AREDS2 participants to evaluate varying levels of zinc and the potential for elimination of β-carotene, which increases the risk of lung cancer in smokers.

PARTICIPANTS: A total of 4203 participants aged 50-85 years with bilateral intermediate AMD (bilateral large drusen ≥125 μm) or intermediate AMD in one eye and advanced AMD in the other eye were enrolled at 82 clinical centers between 2006 and 2008.

METHODS: Participants attended annual clinic visits, including eye examinations, visual acuity, slit lamp, intraocular pressure, and imaging that included stereoscopic 30° color fundus (fields 1-3) and fundus reflex images in all participants, while fundus autofluorescence images and spectral-domain OCT images were acquired in selected clinics. Telephone contacts at 3 and 6 months and annually thereafter collected adverse events and reinforced visit compliance.

MAIN OUTCOME MEASURES: Progression to advanced AMD (central geographic atrophy or neovascular AMD), incidence of cataract surgery, and loss of ≥15 letters (≥3 lines) of visual acuity from baseline.

RESULTS: Controlled-access data are archived under the database of Genotypes and Phenotypes (dbGaP) website with the accession number phs002015.v2.p1. The data elements include main-study phenotype tables plus multiple ancillary-study tables with cardiovascular, cognitive, nutritional biochemistry, and genetic data. Additional data include dietary assessments, image gradings, visual acuity testing, and cataract surgery documentation. Blood or saliva from >2000 participants was collected; exome-chip data from >1800 and whole-genome sequencing from 1363 participants, including 488 who also participated in the original AREDS, are available under the International AMD Genomics Consortium and dbGaP.

CONCLUSIONS: The AREDS2 dataset's rigorous interventional design, standardized longitudinal ophthalmic imaging gradings, comprehensive dietary and genetic information, and ancillary cardiovascular and cognitive assessments constitute an invaluable resource for elucidating AMD progression, informing nutritional strategies, and artificial intelligence-driven diagnostics.

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

@article {pmid41449919,
year = {2025},
author = {Tang, J and Chen, J and Li, Z and Zhang, G and Zhu, L and Li, H and Su, W and Qin, S},
title = {Genetic Correlation and Mendelian Randomization Analyses Reveal Causal Links Between Metabolic-Associated Diseases or Risk Factors and Major Eye Diseases.},
journal = {Current eye research},
volume = {},
number = {},
pages = {1-12},
doi = {10.1080/02713683.2025.2585338},
pmid = {41449919},
issn = {1460-2202},
abstract = {PURPOSE: This study aims to elucidate the causal relationships and shared genetic architecture between metabolic-associated diseases and risk factors-including hypertension, type 1 diabetes (T1D), type 2 diabetes (T2D), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body mass index (BMI)-and primary vision-threatening eye disorders, involving glaucoma, cataracts, refractive disorders, and age-related macular degeneration (AMD).

METHODS: We analyzed genome-wide association study (GWAS) summary statistics from > 500 000 individuals of European ancestry in the FinnGen, UK Biobank, and MRC-IEU databases to ensure adequate sample size. Linkage disequilibrium score regression (LDSC) was applied to estimate genetic correlations, while two-sample Mendelian randomization (MR) was performed to assess causal effects. Furthermore, a bidirectional Mendelian Randomization was further conducted to examine the directionality of associations between hypertension and cataracts.

RESULTS: This study was the first to reveal genetic correlations and causal effects of hypertension on cataracts, particularly senile cataracts. MR analysis provided evidence that hypertension is causally associated with an increased risk of cataracts, particularly senile cataract, whereas the reverse association was not supported. Additionally, LDL cholesterol was suggested as a protective factor for AMD, while HDL cholesterol was associated with an increased risk. The LDSC analysis also indicated a suggestive genetic correlation between T2D and both cataracts and glaucoma, but not for T1D.

CONCLUSION: This study provides comprehensive evidence of genetic correlations and potential causal relationships between metabolic-associated conditions and major eye diseases contributing to vision loss.},
}

@article {pmid41448679,
year = {2025},
author = {Oldham, E and Hall, RH and Jones, G and Modi, J and Ward, S and Magee, T and Fitzgerald, K and Magana, K and Hughes, G and Ford, AI and Vassar, M},
title = {Assessing uptake of the macular degeneration core outcome set in clinical trials: a cross-sectional study.},
journal = {BMJ open},
volume = {15},
number = {12},
pages = {e104705},
doi = {10.1136/bmjopen-2025-104705},
pmid = {41448679},
issn = {2044-6055},
mesh = {Humans ; Cross-Sectional Studies ; *Macular Degeneration/therapy ; *Clinical Trials as Topic/standards ; *Outcome Assessment, Health Care/standards ; },
abstract = {PURPOSE: Establishing comparability between measured outcomes in clinical trials poses a significant obstacle for systematic reviewers. Core outcome sets (COSs) were developed to address this issue. The macular degeneration (MD) COS is designed to standardise outcome measurement across clinical trials for MD. This study investigates the uptake of the MD COS in standardising outcome measurement across clinical trials.

DESIGN: Cross-sectional analysis METHODS: We conducted a search on ClinicalTrials.gov to locate MD clinical trials that were registered 5 years prior to COS publication through the search date of 26 June 2023 and obtained a pool of 2152 registered studies. After applying various inclusion and exclusion criteria, we analysed 159 trials. We then analysed the COS uptake using an interrupted time series analysis (ITSA) and performed performed analyses of variance (ANOVAs) and Pearson correlations to evaluate associations between trial characteristics and outcome measurement.

RESULTS: ITSA showed no significant change in uptake following the MD COS (2016): mean percentage of completion of the COS increased by 0.24% per month before publication (p=0.27) and by 0.07% per month after publication (p=0.62), indicating no meaningful post-publication slope change in COS use. For context, visual acuity was most commonly measured, while several patient-reported and disutility domains were infrequently captured.

CONCLUSION: No discernible patterns in COS usage for MD trials were observed. We recommend further collaboration between regulators and COS developers to help with COS uptake. Additionally, we suggest that further studies analyse adherence to COSs in respect to regulatory recommendations.},
}

Humans
Cross-Sectional Studies
*Macular Degeneration/therapy
*Clinical Trials as Topic/standards
*Outcome Assessment, Health Care/standards

@article {pmid41448386,
year = {2025},
author = {Wang, X and Delle, C and Nedergaard, M and Wostyn, P},
title = {Glymphatic Transport and Ocular Diseases.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101433},
doi = {10.1016/j.preteyeres.2025.101433},
pmid = {41448386},
issn = {1873-1635},
abstract = {The high metabolic demand of retinal neurons requires tightly regulated mechanisms to maintain homeostasis and ensure the efficient clearance of metabolic waste and excess water. Recent studies have identified a glymphatic-like system in the rodent eye, and growing evidence supports the existence of a similar pathway in the human eye, facilitating fluid exchange and waste removal. The ocular glymphatic system supports bidirectional flow along the optic nerve - anterograde from the retina and retrograde from the brain. In this review, we integrate findings from preclinical models and clinically grounded hypotheses to identify key contributors to glymphatic dysfunction in ocular diseases. These include impaired laminar barrier integrity, pathological perivascular space expansion, aquaporin-4 abnormalities, immature vasculature, and pathological immune activation. Glymphatic impairment has been implicated in murine models of glaucoma, diabetic retinopathy, and ocular manifestations of Alzheimer's disease. Additionally, disrupted glymphatic flow is suspected in papilledema, spaceflight associated neuro-ocular syndrome, and Terson syndrome. We further explore novel associations between glymphatic dysfunction and other blinding disorders such as myopic optic neuropathy, age-related macular degeneration, neuromyelitis optica spectrum disorders, and retinal vasculitis. In delineating these mechanistic links, this review provides a conceptual framework to guide future research in glymphatic contributions to ocular diseases.},
}

@article {pmid41446234,
year = {2025},
author = {Lewis, TR and Castillo, CM and Phan, S and Shores, CR and Hayase, KK and Kim, KY and Ellisman, MH and Alekseev, O and Burns, ME and Arshavsky, VY},
title = {RPE pseudopods maintain photoreceptor outer segment renewal despite subretinal space expansion in Adam9 knockout mice.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2025.12.16.694731},
pmid = {41446234},
issn = {2692-8205},
abstract = {Vision begins in the outer segment compartment of photoreceptor cells, which is constantly renewed through the addition of membrane material at its base and ingestion of mature membranes at its tip by the retinal pigment epithelium (RPE). The close apposition of outer segments to the RPE is believed to be critical for maintaining this renewal process. Yet, in several retinal diseases, expansion of the subretinal space separating photoreceptors from the RPE does not immediately impact photoreceptor functionality. Here, we analyzed outer segment function and renewal in the Adam9 knockout mouse characterized by a major expansion of the subretinal space. Surprisingly, photoreceptor-RPE separation affected neither the sensitivity of photoreceptor light-responses nor the normal rate of outer segment renewal in this mouse prior to the onset of photoreceptor degeneration. The latter is achieved through the formation of elongated RPE "pseudopods" extending across the enlarged subretinal space to ingest outer segment tips. This work suggests that pseudopod formation may underlie the persistence of photoreceptor function in human diseases accompanied by photoreceptor-RPE separation, such as vitelliform macular dystrophy or age-related macular degeneration associated with subretinal drusenoid deposits.},
}

@article {pmid41444944,
year = {2025},
author = {Khathami, AA and Baklola, M and Alalyani, MA and Aljuaid, AT and Alsaeed, R and Ghramah, AA and Aljuaid, OT and AlGarni, RH and Alshahrani, RS and Aldreweash, RS and Alshehri, RS and Albishi, SA and Almutairi, GM and Al-Bawah, N and Ghaith, KAA},
title = {Multimodal artificial intelligence in retinal vascular and neovascular macular diseases: a systematic review of diagnostic and prognostic applications.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-025-04561-3},
pmid = {41444944},
issn = {1471-2415},
abstract = {BACKGROUND: Retinal vascular diseases, including diabetic retinopathy (DR) and retinal vein occlusion (RVO), and neovascular macular diseases such as neovascular age-related macular degeneration (nAMD) are leading causes of vision loss worldwide. With the rapid growth of artificial intelligence (AI), multimodal approaches that integrate diverse imaging modalities and clinical data have emerged as powerful tools for improving diagnosis, prognosis, and risk stratification.

METHODS: This systematic review, conducted according to PRISMA 2020 guidelines, synthesized evidence on the diagnostic and prognostic applications of multimodal AI in retinal vascular diseases. Six databases (PubMed, Embase, Scopus, Web of Science, IEEE Xplore, and Cochrane Library) were searched for English-language studies published between 1 January 2019 and 1 November 2025. Eligible studies applied AI or machine learning models integrating two or more data modalities for diagnosis, prognosis, or prediction in DR, RVO, or AMD. Data extraction, quality appraisal, and narrative synthesis were performed.

RESULTS: From 11,659 identified records, 12 studies met the eligibility criteria. Multimodal AI systems consistently outperformed unimodal models and, in several cases, exceeded expert ophthalmologist performance. Diagnostic accuracy for AMD and polypoidal choroidal vasculopathy (PCV) ranged from 87% to 96%, with fusion-based approaches achieving area under the curve (AUC) values up to 0.989. Prognostic models predicting treatment response or recurrence in nAMD and RVO achieved AUCs between 0.972 and 0.980, surpassing both clinician and single-modality baselines. Hybrid and foundation models integrating imaging, clinical, and textual data demonstrated promising results but variable robustness. Most studies were retrospective, single-center, and exhibited moderate-to-high risk of bias, emphasizing the need for larger, prospective, multicenter validation to establish clinical applicability and generalizability.

CONCLUSION: Multimodal AI demonstrates superior diagnostic and prognostic performance compared to unimodal models and, in some cases, outperforms expert clinicians in managing retinal vascular diseases. Integrating complementary data sources, such as OCT, fundus imaging, and clinical information, enhances model accuracy and generalizability.},
}

@article {pmid41443801,
year = {2025},
author = {Ouchi, C and Hosokawa, MM and Kimura, S and Shiode, Y and Matoba, R and Morita, T and Morizane, Y},
title = {Real-World Outcomes of Anti-Vascular Endothelial Growth Factor Therapy for Neovascular Age-Related Macular Degeneration in Patients Aged 85 or Older.},
journal = {Acta medica Okayama},
volume = {79},
number = {6},
pages = {405-412},
doi = {10.18926/AMO/69842},
pmid = {41443801},
issn = {0386-300X},
mesh = {Humans ; Aged, 80 and over ; Male ; Female ; *Angiogenesis Inhibitors/therapeutic use/administration & dosage ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Treatment Outcome ; *Macular Degeneration/drug therapy ; Visual Acuity ; Ranibizumab/therapeutic use/administration & dosage ; Intravitreal Injections ; Choroidal Neovascularization/drug therapy ; Retrospective Studies ; },
abstract = {We investigated the treatment outcomes of patients aged ≥85 years with neovascular age-related macular degeneration (nAMD) who received anti-vascular endothelial growth factor (anti-VEGF) therapy using either treat-and-extend (TAE) or pro re nata (PRN) regimens for 1 year in real-world clinical practice. Eighty-five eyes from 85 patients were included. Among them, types 1, 2, and 3 macular neovascularization and polypoidal choroidal vasculopathy were present in 27.1%, 17.6%, 18.8%, and 36.5%, respectively. TAE and PRN regimens were used in 43.5% and 56.5% of patients, respectively. At baseline, the PRN group was older and had worse best-corrected visual acuity (BCVA), greater central retinal thickness, and more intraretinal fluid than the TAE group. In the TAE group, the mean number of injections was 7.6, BCVA improved significantly, and all retinal fluid rates decreased. In the PRN group, the mean number of injections was 3.9, BCVA remained unchanged, and the rates of macular fibrosis and atrophy increased. No serious adverse events were observed in either group. Anti-VEGF therapy was safe for patients aged ≥ 85 years with nAMD, and the TAE regimen effectively improved BCVA in this population. BCVA remained unchanged in the PRN-treated patients, with baseline disease severity and/or undertreatment potentially influencing the outcomes.},
}

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

@article {pmid41443587,
year = {2025},
author = {Kwan, WC and Brunton, EK and Goris, T and Begeng, JM and Kameneva, T and Stoddart, PR and Ibbotson, MR and Richardson, RT and Tong, W},
title = {Hybrid Optogenetic and Electrical Stimulation of Retinal Ganglion Cells for Artificial Vision.},
journal = {Brain stimulation},
volume = {},
number = {},
pages = {103012},
doi = {10.1016/j.brs.2025.103012},
pmid = {41443587},
issn = {1876-4754},
abstract = {INTRODUCTION: Millions of adults worldwide experience severe visual impairment due to photoreceptor loss from retinal diseases such as retinitis pigmentosa and macular degeneration. Retinal prostheses that provide artificial vision by stimulating the surviving retinal ganglion cells (RGCs) have emerged as a promising therapy. However, all clinically approved retinal prostheses that use electrical stimulation face the issue of electrical spread. As such, the quality of restored vision provided by existing devices has been limited. Optogenetic approaches provide greater spatial precision, however, they have poor temporal properties compared to electrical stimulation.

MATERIALS AND METHODS: We developed an opto-electrical hybrid approach and surveyed this stimulation strategy in the retina of two animal models: normal-sighted transgenic mice that express ChR2-H134R in a sub-population of RGCs and the degenerated retina of Royal College of Surgeons rats with residual RGCs transduced with ChrimsonR. We conducted whole-cell patch clamp recordings and measured calcium transients with the biosensor GCaMP7s to determine single-cell and population responses to hybrid stimulation, respectively.

RESULTS: Hybrid stimulation reduced both electrical and optogenetic activation thresholds. Optical thresholds could be halved with electrical supplementation and synergistically, the opto-electrical coupling reduced the electrical intensity requirements to elicit action potentials by ∼50% (p <0.0001). Additionally, hybrid stimulation evoked significantly higher firing frequencies, by an order of up to 2x, when compared to electrical or optical-only methods (p < 0.0001). These properties of hybrid stimulation were replicated in the diseased retina, where the reduced activation thresholds contributed to significantly reduced spread of activation compared to electrical stimulation alone (p<0.05), a challenge that persists in devices that utilise extracellular electrical stimulation. Hybrid stimulation improved the spatial resolution of RGC activation when applied at nerve-electrode spacing reflective of current epiretinal and suprachoroidal devices.

CONCLUSION: As hybrid stimulation permits more localized stimulation when compared to electrical-only stimulation methods and can improve response reliability whilst reducing optical intensity thresholds when compared to optical-only methods, hybrid stimulation may not only improve the resolution and refresh rate of future visual prostheses but may also provide greater control in neuromodulation for any bionic device that interfaces with neural tissue.},
}

@article {pmid41443408,
year = {2025},
author = {Joo, JH and Zhao, AH and Chalasani, M and Allan, KC and Rachitskaya, AV},
title = {Impact of Glucagon-like Peptide-1 Receptor Agonists on Age-Related Macular Degeneration at a Tertiary Ophthalmology Center.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2025.12.014},
pmid = {41443408},
issn = {2468-6530},
abstract = {OBJECTIVE: There is ongoing debate in the literature on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RA) on age-related macular degeneration (AMD). This study examines the effect of GLP-1RA on the risk of AMD development compared to other glucose-lowering medications at a single ophthalmology center.

DESIGN: Retrospective cohort study.

SUBJECTS: 30,515 GLP-1RA users, 48,906 SGLT-2i, 286,066 metformin, and 164,361 insulin users aged 50+ years had 1-year minimum drug duration between 2016 and 2025. After propensity score matching (PSM), each cohort included 7,561 patients. Patients with diabetic macular edema, severe or proliferative diabetic retinopathy, and with history of prior retinal surgeries were excluded.

METHODS: The relative risk of developing nonexudative AMD was measured at yearly drug duration intervals up to 3 years using logistic regression models controlling for age, sex, race, smoking status, and HbA1C %. Manual review was performed on a random sampling of AMD cases to optimize accuracy. Cox proportional hazards (CPH) validation analyses in PSM cohorts were performed, matching additionally for BMI, history of hypertension, chronic kidney disease, and diabetes duration.

MAIN OUTCOME MEASURES: The primary outcome was the relative risk of nonexudative AMD up to 3 years on GLP-1RAs compared to alternate anti-hyperglycemic agents.

RESULTS: GLP-1RA was associated with decreased risk of nonexudative AMD compared to metformin and insulin at all three years and compared to SGLT-2i only after 3 years of use (3 years: metformin RR=0.25, 95% CI 0.14-0.41, insulin RR=0.28, 95% CI 0.15-0.46, SGLT-2i RR=0.42, 95% CI 0.22-0.74). In PSM cohorts, CPH analyses showed a reduced risk only compared to insulin (HR=0.45, 95% CI 0.27-0.76).

CONCLUSION: GLP-1RA use was associated with lower risk of nonexudative AMD compared to metformin, insulin, and SGLT-2i in logistic regression models. The risk reduction persisted for insulin in CPH analyses in smaller PSM cohorts.},
}

@article {pmid41441525,
year = {2025},
author = {Cohen, R and Kerman, T and Trivizki, O},
title = {Bilateral Sterile Intraocular Inflammation Following Intravitreal Aflibercept 8 mg Injections: A Case Report.},
journal = {Reports (MDPI)},
volume = {8},
number = {4},
pages = {},
doi = {10.3390/reports8040249},
pmid = {41441525},
issn = {2571-841X},
abstract = {Background and Clinical Significance: To report a case of bilateral sterile intraocular inflammation following intravitreal aflibercept 8 mg (Eylea HD) injections. Case Presentation: An 89-year-old woman with bilateral neovascular age-related macular degeneration (nAMD) developed blurred vision and mild ocular pain in both eyes four days after receiving aflibercept 8 mg injections in both of her eyes. Examination revealed a marked anterior chamber reaction with Descemet's folds, 2+ vitreous cells, and 3+ vitreous haze bilaterally. Intraocular pressures were normal, and B-scan ultrasonography confirmed attached retinas with bilateral vitreous opacities. The clinical presentation initially raised concern for infectious endophthalmitis; however, the bilateral presentation, quiet conjunctivae, and prior history of sterile inflammation after aflibercept 2 mg supported a diagnosis of sterile intraocular inflammation. The patient was hospitalized and treated with intensive topical corticosteroids, antibiotics, and cycloplegics, resulting in rapid improvement and complete resolution of symptoms within four days with recovery of baseline vision. Conclusions: Intravitreal aflibercept 8 mg can be associated with bilateral sterile intraocular inflammation, even in patients who previously tolerated standard-dose aflibercept. Awareness of this potential adverse event is essential to avoid unnecessary interventions and to guide appropriate management.},
}

@article {pmid41439341,
year = {2025},
author = {Moore, NC and Song, YE and Gulyayev, AV and Miskimen, KL and Laux, RA and Lynn, A and Fuzzell, SL and Hochstetler, SD and Miller, D and Caywood, LJ and Clouse, JE and Herington, SD and Wang, W and Wang, P and Liu, Y and Dorfsman, DA and Nittala, MG and Sadda, SR and Stambolian, D and Ogrocki, PK and Lerner, AJ and Cuccaro, ML and Vance, JM and Scott, WK and Pericak-Vance, M and Haines, JL},
title = {Basic Science and Pathogenesis.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 1},
number = {},
pages = {e106578},
doi = {10.1002/alz70855_106578},
pmid = {41439341},
issn = {1552-5279},
mesh = {Humans ; *Alzheimer Disease/genetics ; High-Temperature Requirement A Serine Peptidase 1 ; Polymorphism, Single Nucleotide/genetics ; *Macular Degeneration/genetics ; Female ; Male ; Aged ; *Complement Factor H/genetics ; *Genetic Predisposition to Disease/genetics ; *Proteins/genetics ; *Serine Endopeptidases/genetics ; Aged, 80 and over ; Risk Factors ; Middle Aged ; },
abstract = {BACKGROUND: Late-onset Alzheimer Disease (LOAD) shares multiple pathologic features and genetic risk factors with Age-related Macular Degeneration (AMD). Amyloid-beta (Ab) forms amyloid plaques in the brain and aggregates with other proteins and lipids to form drusen deposits in the retina of AMD eyes. CFH and HTRA1, genes coding for Ab-processing complement proteins, are the strongest genetic risk factors for AMD, but the association with LOAD has been equivocal. In addition, the APOE e4 allele, LOAD's strongest genetic risk factor, has the opposite effect (e.g. is protective) for AMD. Therefore, we investigated whether the strongest genetic risk factors for AMD, CFH and ARMS2/HTRA1 also influence risk of LOAD.

METHOD: Utilizing our large dataset of mid-Western Amish individuals, we performed single nucleotide polymorphism (SNP) association analysis on the ARMS2/HTRA1 and CFH loci to determine their association with LOAD. This analysis included 152 LOAD cases and 746 cognitively unimpaired controls, all evaluated by consensus review of clinical test results. Those with known AMD were excluded from this study.

RESULT: Our preliminary results found no significant association between LOAD and the individual SNPs defining the CFH or ARMS2/HTRA1 loci. As these genes are in regions of strong linkage disequilibrium, these SNPs define a small set of extended haplotypes, which have known differential impact on AMD.

CONCLUSION: Single SNP association analyses did not expose any significant associations between LOAD and single SNPs at the CFH or ARMS2/HTRA1 loci. Examining the haplotype association with LOAD will allow for increased power and better understanding of the risk these two loci confer to LOAD.},
}

Humans
*Alzheimer Disease/genetics
High-Temperature Requirement A Serine Peptidase 1
Polymorphism, Single Nucleotide/genetics
*Macular Degeneration/genetics
Female
Male
Aged
*Complement Factor H/genetics
*Genetic Predisposition to Disease/genetics
*Proteins/genetics
*Serine Endopeptidases/genetics
Aged, 80 and over
Risk Factors
Middle Aged

@article {pmid41439218,
year = {2026},
author = {Vo, A and Shen, LL and Pak, I and Taha, AT and Diaz, AZ and Stewart, JM},
title = {Association between Baseline Subfoveal Choroidal Thickness and Anatomical and Functional Outcomes in Geographic Atrophy.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {100986},
pmid = {41439218},
issn = {2666-9145},
abstract = {OBJECTIVE: To investigate the relationship between baseline subfoveal choroidal thickness (SFChT) and both visual outcomes and geographic atrophy (GA) growth rate, and to assess whether SFChT mediates the treatment effect of oral metformin on GA progression.

DESIGN: Secondary analysis of a randomized controlled trial.

PARTICIPANTS: Seventy eyes (34 metformin; 36 observation) from 44 participants (21 metformin; 23 observation) with GA and ≥6 months of follow-up in the METformin for the MINimization of Geographic Atrophy Progression study.

METHODS: Subfoveal choroidal thickness was measured from baseline OCT. We calculated GA area growth rate by subtracting the GA area at the first visit from the GA area at the last visit and dividing the result by the time interval. Geographic atrophy perimeter-adjusted growth rate was calculated by dividing GA area growth rate by the mean GA perimeter between the first and last visit.

MAIN OUTCOME MEASURES: Longitudinal changes in GA area and visual acuity.

RESULTS: Baseline SFChT was not significantly associated with baseline GA area (P = 0.51), baseline best-corrected visual acuity (BCVA) (P = 0.49), baseline low-luminance visual acuity (LLVA) (P = 0.85), or rim area focal hyperautofluorescence signals (P = 0.29). Baseline SFChT was not significantly associated with GA perimeter-adjusted growth rate (P = 0.74), the decline rate of BCVA (P = 0.14), and the decline rate of LLVA (P = 0.71). However, sensitivity analyses in GA subgroups found that baseline SFChT was associated with decreased rate of BCVA decline in patients with foveal-involving GA (Spearman ρ = 0.03, P = 0.03). Baseline SFChT did not significantly influence the effect of oral metformin on GA perimeter-adjusted growth rate (P = 0.78).

CONCLUSIONS: Greater baseline SFChT was significantly associated with slower BCVA decline in eyes with foveal-involving GA, suggesting a possible localized role of choroidal thickness in preserving central vision. However, SFChT was not associated with GA growth rate, LLVA decline, or baseline anatomical and functional measures. It also did not mediate the effect of oral metformin. While SFChT lacks prognostic value for GA progression overall, it may hold limited relevance for central vision outcomes in foveal-involving GA.

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

@article {pmid41439215,
year = {2026},
author = {Ueda-Arakawa, N and Sato, Y and Miyake, M and Takahashi, A and Mori, Y and Miyara, Y and Hara, C and Kitajima, Y and Maruko, R and Kawai, M and Ohnaka, M and Koizumi, H and Maruyama-Inoue, M and Yanagi, Y and Iida, T and Kondo, M and Sakamoto, T and Tsujikawa, A},
title = {Impact of Reticular Pseudodrusen on Clinical and Ocular Characteristics and Progression Rate of Geographic Atrophy in Japanese Patients.},
journal = {Ophthalmology science},
volume = {6},
number = {2},
pages = {100984},
pmid = {41439215},
issn = {2666-9145},
abstract = {PURPOSE: To elucidate the impact of reticular pseudodrusen (RPD) on the clinical and ocular characteristics and progression rate of geographic atrophy (GA) in Japanese patients.

DESIGN: A multicenter, retrospective, observational cohort study.

PARTICIPANTS: A total of 173 eyes from 173 Japanese patients (135 with conventional GA and 35 with pachychoroid GA) were included; 79 eyes with conventional GA were included in the follow-up group.

METHODS: Reticular pseudodrusen status, GA type (conventional/pachychoroid), GA location (central/noncentral), GA pattern (unifocal/multifocal), subfoveal choroidal thickness (SFCT), and fellow-eye status were assessed using multimodal imaging. The GA progression rate was calculated in both mm[2]/year and mm/year (square root transformation [SQRT]) after semiautomatic measurement of the GA area on fundus autofluorescence images.

MAIN OUTCOME MEASURES: Clinical and ocular characteristics and progression rate of GA according to RPD status.

RESULTS: Reticular pseudodrusen were observed in 42.4% (73 eyes) of the 173 study eyes, 54.1% of the eyes with conventional GA, and none of the eyes with pachychoroid GA. Among patients with conventional GA, those with RPD were significantly more female (56.2 vs. 30.6%, P = 0.003), had better visual acuity (0.31 vs. 0.50 in logarithm of the minimum angle of resolution, P = 0.03), a smaller SFCT (141.7 vs. 185.0 μm, P = 0.02), higher prevalence of noncentral (56.2 vs. 32.3%, P = 0.005) and multifocal GA (68.5 vs. 29.0%, P < 0.001), and bilateral late age-related macular degeneration (AMD) (93.1 vs. 65.0%, P < 0.0001) than those without RPD. The GA progression rate was significantly higher in eyes with RPD than in eyes without RPD (0.34 vs. 0.18 mm/year [SQRT], P < 0.001).

CONCLUSIONS: Reticular pseudodrusen are frequently observed in Japanese patients with conventional GA. Clinical and ocular characteristics differ according to the RPD status, similarly in White patients. Geographic atrophy in the presence of RPD progresses rapidly, at a rate comparable to that in White patients, and most patients with RPD exhibit bilateral late AMD. Given that RPD in eyes with GA constitutes a strong risk factor for both fast GA progression and bilateral late AMD, GA with RPD should be treated at an early stage prior to foveal involvement, even though GA in Asians has been reported to progress slowly.

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

@article {pmid41438708,
year = {2025},
author = {Liu, X and Wang, Y and Huang, J and Chen, L and Cai, T and Wang, Q and Li, S and Yu, G and Chen, Y and Luo, D and Ding, X},
title = {Sustained suppression of choroidal neovascularization by intraocularly stable tetrahedral network encapsulated miR-22-3p.},
journal = {Materials today. Bio},
volume = {35},
number = {},
pages = {102578},
pmid = {41438708},
issn = {2590-0064},
abstract = {Choroidal neovascularization (CNV), characterized by abnormal vessel growth and vascular leakage, is the hallmark of wet age-related macular degeneration (wAMD) and a leading cause of irreversible vision loss. Although anti-vascular endothelial growth factor (VEGF) therapies remain the current standard, their frequent administration and limited long-term efficacy highlight the need for novel treatments. Here, we developed a miR-22-3p-loaded tetrahedral framework nucleic acids (tFNAs-miR22) nanostructure and evaluated its efficacy in CNV suppression. The nanocomplex was structurally validated, exhibiting high assembly fidelity and superior intraocular stability compared to serum conditions. In a laser-induced CNV mouse model, a single intravitreal injection of tFNAs-miR22 significantly reduced lesion size and leakage by day 10, with efficacy comparable to aflibercept. In a rat model of stable and long-lasting CNV, tFNAs-miR22 demonstrated durable inhibition of vascular leakage by Day 21, showing greater persistence compared to aflibercept. This effect was dose-dependent, with the high-dose group outperforming aflibercept in suppressing leakage. Transcriptomic profiling of hypoxia-challenged HUVECs further revealed that tFNAs-miR22 modulates angiogenic pathways, including suppression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) axis. These findings demonstrate the potent and long-lasting therapeutic effects of tFNAs-miR22, supporting its promise as a next-generation, gene-regulatory nanotherapy for sustained inhibition of CNV.},
}

@article {pmid41437494,
year = {2026},
author = {Jianjun, Y},
title = {Bilateral hypertensive retinopathy (grade 4): Case report and review of the literature on intravitreal injection anti-VEGF therapy.},
journal = {Clinical and experimental hypertension (New York, N.Y. : 1993)},
volume = {48},
number = {1},
pages = {2604831},
doi = {10.1080/10641963.2025.2604831},
pmid = {41437494},
issn = {1525-6006},
mesh = {Humans ; Intravitreal Injections ; *Hypertensive Retinopathy/drug therapy/complications ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Male ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Female ; Middle Aged ; Macular Edema/drug therapy/etiology ; Aged ; Visual Acuity ; Ranibizumab ; Choroidal Neovascularization/etiology/drug therapy ; Treatment Outcome ; Bevacizumab ; },
abstract = {OBJECTIVE: To introduce bilateral hypertensive retinopathy (HR) (grade 4) complicated with macular edema (ME) patients with binocular intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) treatment.

METHODS: Three cases of hypertensive retinopathy were observed. The fundus examination was consistent with HR (grade 4). The patients received anti-VEGF intraocular injection.

RESULTS: The patient's ME and optic nerve edema were significantly reduced, visual acuity was significantly improved, and a case of secondary choroidal neovascularization (CNV) in the fundus of HR (grade 4) was also noted.

CONCLUSIONS: The use of intravitreal anti-VEGF agents in stage IV hypertensive retinopathy appears satisfactory but not perfect. In severe cases with vitreous hemorrhage, early injection avoids vitrectomy.},
}

Humans
Intravitreal Injections
*Hypertensive Retinopathy/drug therapy/complications
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
Male
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
Female
Middle Aged
Macular Edema/drug therapy/etiology
Aged
Visual Acuity
Ranibizumab
Choroidal Neovascularization/etiology/drug therapy
Treatment Outcome
Bevacizumab

@article {pmid41435998,
year = {2025},
author = {Li, Y and Yuan, S and Zhang, C and Hu, P and Huang, X and Zhou, J and Liu, D and Zhou, X},
title = {Engineered nanoparticles for subconjunctival delivery to the retinal pigment epithelium: A multi-target therapy for dry AMD.},
journal = {Journal of controlled release : official journal of the Controlled Release Society},
volume = {},
number = {},
pages = {114563},
doi = {10.1016/j.jconrel.2025.114563},
pmid = {41435998},
issn = {1873-4995},
abstract = {Dry age-related macular degeneration (dAMD) is a leading cause of irreversible blindness, driven by oxidative stress-induced retinal pigment epithelial (RPE) cell degeneration. Existing therapies suffer from poor bioavailability and insufficient multi-pathway modulation. To address this, we developed P(R)/T-Lf nanoparticles, a subconjunctivally administered nanotherapy co-loaded with resveratrol (Res) and dual-functionalized with trimethyl chitosan (TMC) and lactoferrin (Lf). The P(R)/T-Lf NPs exhibited: (1) prolonged ocular retention via TMC-mediated mucoadhesion and enhanced RPE targeting through Lf receptor binding; (2) sustained Res release over 35 days, effectively scavenging reactive oxygen species and inhibiting ferroptosis by downregulating NOX2, ACSL4, and COX2 while restoring GPX4; (3) superior therapeutic outcomes in NaIO3-induced dAMD models, preserving retinal morphology and function. Comparative studies demonstrated that P(R)/T-Lf NPs outperformed non-targeted controls. This nanoplatform provides a translation-ready strategy to concurrently tackle oxidative stress, inflammation, and ferroptosis via sustained, targeted delivery, representing a transformative approach for dAMD therapy.},
}

@article {pmid41435247,
year = {2025},
author = {Gu, X and Terebuh, P and Xu, R and Kaelber, D and Davis, P},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e099176},
doi = {10.1002/alz70860_099176},
pmid = {41435247},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; Retrospective Studies ; *Blindness/epidemiology/etiology ; *Macular Degeneration/epidemiology/complications ; Middle Aged ; *Alzheimer Disease/epidemiology ; Aged, 80 and over ; *Public Health ; *Dementia/epidemiology ; Risk Factors ; Cohort Studies ; Dementia, Vascular/epidemiology ; },
abstract = {BACKGROUND: Research suggests a link between blindness, age-related macular degeneration (AMD), and a higher risk of dementia. Since AMD can lead to blindness, it remains unclear whether this elevated risk is due to the disease's underlying pathology or its ability to cause blindness. The presence of Aβ amyloid proteins in AMD retinas' drusen adds further complexity. This study aims to determine whether the dementia risk is attributed to AMD pathogenesis or the resulting blindness.

METHOD: We conducted a retrospective cohort study using TriNetX, a deidentified electronic health record platform, focusing on patients aged over 50 years. Non-blind patients with exudative AMD (n = 36,138) and non-exudative AMD (n = 102,494) were compared to non-blind individuals without AMD (n = 1,901,246). We calculated hazard ratios (HR) for Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia over five years. Additionally, we compared blind patients (n = 59,835) with non-blind patients (n = 920,118) for the same outcomes. Cohorts were propensity-matched for age, gender, race/ethnicity, and other dementia risk factors. Sensitivity analyses assessed dementia risk across age groups and by AMD status in blind patients.

RESULT: AMD in non-blind patients was either not associated with dementia or linked to a reduced risk, while blindness showed a strong positive association. Exudative AMD showed no increased VaD risk (HR=0.825, CI = [0.68, 1.001]) but had a significantly reduced risk of AD (HR=0.815, CI=[0.697, 0.952]) and all-cause dementia (HR=0.792, CI=[0.766, 0.818]). Non-exudative AMD also showed no significant risk of VaD (HR=0.893, CI=[0.791, 1.009]) but had a significantly reduced risk of AD (HR=0.86, CI = [0.782, 0.947]) and all-cause dementia (HR=0.862, CI=[0.818, 0.908]). Blindness was linked to a significantly increased risk of AD (HR=1.429, CI = [1.276, 1.602]), VaD (HR=1.665, CI=[1.488, 1.862]), and all-cause dementia (HR=1.383, CI=[1.304, 1.466]). This pattern is consistent across various age groups in patients above 50 years old and in blind patients as well.

CONCLUSION: AMD is associated with a mildly reduced risk of Alzheimer's dementia when controlling for blindness. Prior reports linking AMD to dementia likely reflect the impact of blindness rather than shared pathology. This protective effect may be due to AMD treatments like AREDS2 vitamins, which support cognitive health.},
}

Humans
Male
Female
Aged
Retrospective Studies
*Blindness/epidemiology/etiology
*Macular Degeneration/epidemiology/complications
Middle Aged
*Alzheimer Disease/epidemiology
Aged, 80 and over
*Public Health
*Dementia/epidemiology
Risk Factors
Cohort Studies
Dementia, Vascular/epidemiology

@article {pmid41433985,
year = {2025},
author = {Gillis, G and Blane, J and Patel, R and Fynes-Clinton, S and Farafontova, I and Makan, D and Martos, L and Raymont, V and Suri, S and Griffanti, L and Mackay, CE},
title = {Public Health.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 6},
number = {},
pages = {e105761},
doi = {10.1002/alz70860_105761},
pmid = {41433985},
issn = {1552-5279},
mesh = {Humans ; Male ; Female ; Aged ; *Public Health ; Prevalence ; United Kingdom/epidemiology ; *Dementia/epidemiology ; Comorbidity ; Middle Aged ; *Multimorbidity ; Aged, 80 and over ; Cohort Studies ; Chronic Disease/epidemiology ; },
abstract = {BACKGROUND: Multimorbidity across the lifespan, especially during critical age windows, is associated with increased dementia risk. In this study, we sought to characterise the accumulation of long-term conditions (LTCs) in a real-world memory clinic population at the Oxford Brain Health Clinic (OBHC). We contextualise these prevalences with comparison to UK Biobank (UKB).

METHOD: By 2025, medical histories extracted from primary care records were available on the OBHC Research Database for 190 NHS memory clinic patients. 50 LTCs or categories of LTCs were prioritised during extraction and grouped according to body system (Figure 1), recording the first time each diagnosis was made. To align with previous comorbidity lists (Patel et al., medRxiv, 2024), some conditions were merged (e.g., cancers, types of arthritis), and others were extracted from free-text (e.g., anaemia, macular degeneration, osteoporosis, prostate, sleep disorders, hyperlipidaemia), resulting in a list of 31 LTCs for comparison. In line with the OBHC cohort, UKB participants younger than or deceased before age 65 were excluded. A supplementary comparison was performed including only those with a dementia diagnosis, excluding those from UKB who were diagnosed before age 65; only pre-dementia LTCs were considered.

RESULT: On average, OBHC patients had 4 comorbid diagnoses before attending their memory clinic appointment; osteoarthritis and hypertension were most common, with a relative prevalence of 46.8% and 43.7%, respectively (Figure 1). In early adulthood, psychiatric conditions were most prevalent in OBHC patients, but cardiovascular conditions accumulated most rapidly across midlife to become the most prevalent (Figure 2). Of the 10 most prevalent LTCs in the OBHC, arthritis, depression, and IBS were more prevalent than in UKB (Figure 3A). OBHC dementia patients had significantly lower prevalences of hypertension, cardiovascular disease, and anaemia than UKB dementia patients (Figure 3B).

CONCLUSION: Although the rankings of conditions between cohorts were largely similar, we found potentially important differences in the prevalence of LTCs between a large population cohort and a real-world patient sample. Ascertaining comparable data across research and clinical cohorts is a harmonisation challenge that needs to be met so the impact of multimorbidity on brain health can inform the development of personalised interventions.},
}

Humans
Male
Female
Aged
*Public Health
Prevalence
United Kingdom/epidemiology
*Dementia/epidemiology
Comorbidity
Middle Aged
*Multimorbidity
Aged, 80 and over
Cohort Studies
Chronic Disease/epidemiology

@article {pmid41433627,
year = {2025},
author = {Grapentine, S and Hazan, A and Alterini, T and Codirenzi, A and DiGregorio, J and Hitchon, S and Kemp, T and Lin, YP and Mayo, B and Oren, N and Rinaldi, A and Shaked, E and Bornbaum, CC and Visee, R and Bietenhader, M and Boudreau, JM and Naureen, R and Weeks, J and Li, X},
title = {Developing Topics.},
journal = {Alzheimer's & dementia : the journal of the Alzheimer's Association},
volume = {21 Suppl 7},
number = {},
pages = {e108584},
doi = {10.1002/alz70861_108584},
pmid = {41433627},
issn = {1552-5279},
mesh = {Humans ; Aged ; Female ; Male ; Aged, 80 and over ; Middle Aged ; *Alzheimer Disease/diagnostic imaging/diagnosis ; *Retina/diagnostic imaging/pathology ; *Artificial Intelligence ; Positron-Emission Tomography ; Prospective Studies ; Cognitive Dysfunction/diagnostic imaging ; },
abstract = {BACKGROUND: Artificial intelligence (AI)-based retinal hyperspectral imaging (rHSI) represents a promising, non-invasive approach to detecting Alzheimer's disease (AD)-related pathology, offering scalability and potential point-of-care utility. Prior findings from Bio-Hermes-001 demonstrated strong concordance between RetiSpec's rHSI model and amyloid PET (Aβ-PET). Bio-Hermes-002 builds on this work in a racially and clinically diverse cohort. While full rHSI performance data are forthcoming, we report preliminary participant characteristics relevant to real-world deployment of retinal imaging technologies.

METHOD: Bio-Hermes-002 is an ongoing prospective, multi-site study of ∼1,200 participants (n =387enrolled at time of reporting) aged 60-89 (mean 72.1), stratified into cognitively normal, MCI, and mild-to-moderate AD cohorts. Retinal imaging was performed using RetiSpec's rHSI system. Amyloid and Tau PET imaging is ongoing; thus, analyses to date are descriptive. Comparative analysis with PET will be presented.

RESULT: Among enrolled participants, 57.4% were female and the cohort was both racially and ethnically diverse, with 18% of participants identifying as Hispanic or Latino and 19.4% identifying as non-Caucasian. Notably, 19.4% of participants self-reported eye conditions (e.g., n=25 cataracts, n=15 glaucoma, n=9 age-related macular degeneration). Ophthalmologist review of images to confirm prevalence of comorbid eye conditions is forthcoming. The prevalence and distribution of eye conditions emphasizes the importance of validating retinal imaging tools in populations reflective of real-world clinical settings, where such comorbidities are common. Feasibility assessments suggest that high-quality retinal images were obtainable across a broad range of participants, including those with eye conditions (e.g., cataracts), supporting the applicability of AI-based rHSI in heterogeneous clinical populations. Analysis of retinal image quality and its relationship to ocular health status will be presented alongside AI model performance data relative to gold standard PET scans.

CONCLUSION: Preliminary findings from Bio-Hermes-002 reinforce the feasibility of AI-based retinal imaging in diverse and heterogeneous populations. Given the prevalence of ocular comorbidities such as cataracts, validation of retinal biomarkers under real-world conditions is critical. Final results, including RetiSpec's AI model performance against amyloid PET and comparative ensemble analyses, will be presented at the conference.},
}

Humans
Aged
Female
Male
Aged, 80 and over
Middle Aged
*Alzheimer Disease/diagnostic imaging/diagnosis
*Retina/diagnostic imaging/pathology
*Artificial Intelligence
Positron-Emission Tomography
Prospective Studies
Cognitive Dysfunction/diagnostic imaging

@article {pmid41433217,
year = {2025},
author = {Li, Y and Mou, B and Song, X},
title = {Long-Term Trends in the Global Burden of Age-Related Macular Degeneration: Sex Differences, Aging Effects, and Future Projections in Middle-Aged and Older Adults.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1-20},
doi = {10.1159/000550175},
pmid = {41433217},
issn = {1423-0259},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a major cause of irreversible vision loss in middle-aged and older populations worldwide. Understanding its long-term epidemiological trends is essential for anticipating future healthcare needs and guiding preventive strategies. This study characterizes the global, regional, and national burden of AMD in adults aged ≥45 years, with a focus on sex disparities, aging effects, and projected trends Methods: Using data from the Global Burden of Disease Study 2021, we analyzed the prevalence and disability-adjusted life years (DALYs) of AMD across age, sex, region, country, and Socio-Demographic Index (SDI) groups. We applied an Age-Period-Cohort (APC) model to disentangle the effects of aging, temporal changes, and birth cohort on AMD risk. Frontier analysis was conducted to identify best-practice benchmarks in disease burden reduction. The association between SDI and AMD burden was assessed to evaluate health inequities. An Autoregressive Integrated Moving Average (ARIMA) model was used to project age-standardized DALY rates (ASDR) and prevalence rates (ASPR) from 2022 to 2036.

RESULTS: Between 1990 and 2021, the absolute number of AMD cases and DALYs nearly doubled. In 2021, both prevalence and DALY rates increased exponentially with age, with females exhibiting consistently higher rates across all age groups. The APC model indicated a declining trend in AMD risk over successive birth cohorts, suggesting potential improvements in early-life or cumulative risk factors. Notably, the highest age-standardized rates were observed in low-SDI regions, highlighting significant global inequities in disease burden. ARIMA projections suggest a modest but concerning increase in the global ASDR, rising to 6.80 (95% CI: 5.82-7.78) by 2036, with female ASDR reaching 7.46 (95% CI: 6.29-8.63).

CONCLUSIONS: The burden of AMD remains substantial and is projected to grow, particularly among aging populations and in low-resource settings. The persistent sex disparity, especially the elevated burden in elderly women, calls for targeted screening and intervention programs. These findings emphasize the need for equitable, age- and sex-sensitive public health strategies to mitigate the rising impact of AMD in the coming decades.},
}

@article {pmid41432997,
year = {2025},
author = {Liang, L and Song, Z and Li, Y and Li, H},
title = {The global disease burden and associated risk factors of age-related macular degeneration: a comprehensive analysis.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {50},
pmid = {41432997},
issn = {1573-2630},
mesh = {Humans ; *Macular Degeneration/epidemiology ; Male ; Female ; Risk Factors ; Prevalence ; Aged ; Global Burden of Disease/trends ; Middle Aged ; Global Health ; Disability-Adjusted Life Years ; Aged, 80 and over ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is the leading cause of blindness among middle-aged and older adults, bringing a heavy health burden. Understanding the patterns of AMD disease burden and the risk factors associated with early AMD development is crucial for formulating targeted public health policies.

METHODS: We estimated the prevalence of AMD and disability-adjusted life year (DALY) using data from the 2021 Global Burden of Disease (GBD). Our analysis examined trends in prevalence and DALY by age, sex, and sociodemographic index (SDI) at global, regional, and national levels from 1990 to 2021. We performed data analysis using two Mendelian randomization (MR) samples to explore the causal relationship between lipid metabolism, nutrients, and early AMD risk. The primary analysis was conducted using the inverse variance weighting method, along with a range of sensitivity analyses.

RESULTS: In 2021, AMD's DALY was 570,000, the age-standardized prevalence rate (ASPR) was 94.00/100,000 (95% UI, 78.32-114.42), and the age-standardized disability rate (ASDR) was 6.78/100,000 (95% UI, 4.70-9.32). The burden of AMD showed a downward trend during the study period. The disease burden is closely related to socioeconomic development and is unevenly distributed, with a heavier burden in low sociodemographic index (SDI) regions, especially in southern and central sub-Saharan Africa. Age-specific DALYs showed a gradual increasing trend, with female DALYs higher than male DALYs in all age groups. Decomposition analysis showed that population growth led to an increase in AMD DALYs. Projections from the Bayesian Age-Period Cohort (BAPC) model indicate that global AMD DALYs may continue to rise by 2045. Additionally, multivariate Mendelian randomization (MVMR) evaluation results showed that triglycerides (TG) (OR, 0.82; 95% CI, 0.73-0.92; p = 0.001) and high-density lipoprotein (HDL) (OR, 1.15; 95% CI, 1.04-1.28; p = 0.009) were significantly associated with early AMD. For every one standard deviation increase in TG levels, the risk of AMD decreases by an average of 18%. Higher TG levels are a protective factor for early AMD. However, the effect of HDL on AMD is the opposite of that of TG. For every one standard deviation increase in HDL levels, the risk of AMD increases by an average of 15%. Higher HDL levels are a risk factor for AMD.

CONCLUSIONS: AMD remains a major health problem worldwide, especially in low SDI regions. Population growth and aging have the most significant impact on AMD DALYs. HDL was identified as a risk factor, while TG was identified as a protective factor. These findings highlight the need for targeted interventions in low SDI regions, including dietary control, early screening, and addressing socioeconomic factors through balanced dietary plans.},
}

Humans
*Macular Degeneration/epidemiology
Male
Female
Risk Factors
Prevalence
Aged
Global Burden of Disease/trends
Middle Aged
Global Health
Disability-Adjusted Life Years
Aged, 80 and over

@article {pmid41432839,
year = {2025},
author = {Galindo, AM and Ohayon, A and Hod, K and Levin, MF and Geffen, N and Shulman, S},
title = {Real-world evidence of long-term durability and efficacy of faricimab as an advanced treatment line for NVAMD and DME.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {47},
pmid = {41432839},
issn = {1573-2630},
mesh = {Humans ; Retrospective Studies ; Intravitreal Injections ; Male ; Female ; Aged ; *Visual Acuity ; Angiogenesis Inhibitors/administration & dosage ; *Macular Edema/drug therapy/diagnosis ; Follow-Up Studies ; Treatment Outcome ; Tomography, Optical Coherence/methods ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Aged, 80 and over ; Time Factors ; *Wet Macular Degeneration/drug therapy/diagnosis ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Fluorescein Angiography ; Middle Aged ; Antibodies, Bispecific ; },
abstract = {PURPOSE: To evaluate the efficacy and durability of intravitreal Faricimab (Vabysmo) in patients with neovascular age-related macular degeneration (NVAMD) and diabetic macular edema (DME).

METHODS: A retrospective study was conducted at a tertiary ophthalmology center. Eyes with NVAMD or DME which had received previous Anti-vascular endothelial growth factor (A-VEGF) treatment before switching to Faricimab were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and injection intervals were recorded at baseline and follow-up visits of up to 2.5 years.

RESULTS: A total of 192 eyes (160 with NVAMD and 32 with DME) from 155 patients were included. The mean patient age was 79.5 ± 9.6 years, with an average follow-up duration of 468.1 ± 120.4 days from baseline. In the NVAMD cohort, BCVA improved from 0.43 ± 0.33 logMAR at baseline to 0.34 ± 0.30 at 1.5 years (p < 0.05). CST decreased significantly from a mean of 308.3 ± 65.3 Micrometers to 242.4 ± 44.8 Micrometers at two years (p < 0.001). The mean interval between injections increased from a mean of 33.9 ± 9.6 days at baseline to 77.6 ± 42.6 days at two years, reflecting a significant extension throughout the observation period (p < 0.001). In eyes with DME, CST declined from 403.6 ± 121.9 Micrometers at baseline to 303.2 ± 105.2 Micrometers at one year (p < 0.001), while BCVA remained stable. Injection intervals extended from 34.4 ± 10.3 to 60.9 ± 20.5 days at one year (p < 0.001).

CONCLUSION: In this study of previously treated eyes with NVAMD and DME, Faricimab demonstrated sustained anatomical and functional benefits alongside meaningful injection interval extension.},
}

Humans
Retrospective Studies
Intravitreal Injections
Male
Female
Aged
*Visual Acuity
Angiogenesis Inhibitors/administration & dosage
*Macular Edema/drug therapy/diagnosis
Follow-Up Studies
Treatment Outcome
Tomography, Optical Coherence/methods
*Diabetic Retinopathy/drug therapy/diagnosis/complications
Aged, 80 and over
Time Factors
*Wet Macular Degeneration/drug therapy/diagnosis
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Fluorescein Angiography
Middle Aged
Antibodies, Bispecific

@article {pmid41432510,
year = {2025},
author = {Fursova, AZ and Strunina, YV},
title = {[Analysis the frequency of using Aflibercept (8 mg) in the treatment of neovascular age-related macular degeneration and diabetic macular edema compared with other anti-VEGF agents].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {6},
pages = {92-100},
doi = {10.17116/oftalma202514106192},
pmid = {41432510},
issn = {0042-465X},
mesh = {Humans ; *Recombinant Fusion Proteins/administration & dosage ; *Receptors, Vascular Endothelial Growth Factor/administration & dosage ; *Macular Edema/drug therapy/diagnosis/etiology ; Intravitreal Injections/methods ; Angiogenesis Inhibitors/administration & dosage ; *Diabetic Retinopathy/drug therapy/diagnosis/complications ; Treatment Outcome ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Ranibizumab/administration & dosage ; Visual Acuity ; *Macular Degeneration/drug therapy/diagnosis ; },
abstract = {PURPOSE: This study aimed to evaluate the frequency of use of the drug aflibercept in the form of a 114.3 mg/mL, 0.263 mL solution for injection (hereinafter aflibercept 8 mg), compared with alternative anti-VEGF agents in adult patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) over a long-term period (2 years).

MATERIAL AND METHODS: A review of the literature was conducted to assess the frequency of administration of anti-VEGF drugs included in the Vital and Essential Drugs (VED) list as of 01.10.2025. Based on the results of published studies, an indirect comparison was performed evaluating the frequency of administration of aflibercept (114.3 mg/mL, 0.263 mL) with ophthalmic drugs used in clinical practice (aflibercept 40 mg/mL, 0.278 mL; brolucizumab 120 mg/mL, 0.23 mL; ranibizumab 10 mg/mL, 0.23 mL) in patients with nAMD and DME over 2 years of therapy. The difference in the number of injections should be interpreted as follows: a negative value indicates fewer injections of aflibercept 8 mg compared with brolucizumab 6 mg and ranibizumab 0.5 mg, while a positive value corresponds to fewer injections when compared with aflibercept 2 mg (as accepted in the original publication).

UNLABELLED: If the difference in frequency of drug administration was statistically significant, additional assessments were performed: the potential number of avoided injections when using a less frequent dosing regimen, and the potential number of additional patients who could receive such treatment.

RESULTS: Aflibercept 8 mg administered in dosing intervals extended up to 24 weeks for patients with nAMD was associated with a statistically significant reduction in the number of injections compared with aflibercept 2 mg: 2.37 (95% CI: 1.88 to 2.86) and 2.6 (95% CI: 2.11 to 3.09); with brolucizumab 6 mg: -1.82 (95% CI: -2.8 to -0.8) and -1.7 (95% CI: -3.0 to -0.4); with ranibizumab 0.5 mg: -7.17 (95% CI: -8.5 to -5.9) and -3.15 (95% CI: -3.7 to -2.6) in the first and second year, respectively.

UNLABELLED: Aflibercept 8 mg administered in dosing intervals extended up to 24 weeks for patients with DME was associated with a statistically significant reduction in the number of injections compared with aflibercept 2 mg: 3.57 (95% CI: 3.1 to 4.0) and 2.7 (95% CI: 2.1 tot 3.3); with brolucizumab 6 mg: -1.97 (95% CI: -2.5 to -1.4) and -1.56 (95% CI: -2.2 to -1.0) in the first and second year, respectively. In a similar comparison between aflibercept 8 mg and ranibizumab 0.5 mg (extended-interval regimen) in DME patients, the difference in the number of injections was 5.7 injections in both the first and second year; however, the value was calculated without determining the confidence interval (CI), which is a limitation of this study.

CONCLUSIONS: The use of aflibercept 8 mg in the treatment of nAMD and DME demonstrates a reduction in the number of intravitreal injections, accompanied by a significant reduction in the socioeconomic burden.},
}

Humans
*Recombinant Fusion Proteins/administration & dosage
*Receptors, Vascular Endothelial Growth Factor/administration & dosage
*Macular Edema/drug therapy/diagnosis/etiology
Intravitreal Injections/methods
Angiogenesis Inhibitors/administration & dosage
*Diabetic Retinopathy/drug therapy/diagnosis/complications
Treatment Outcome
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Ranibizumab/administration & dosage
Visual Acuity
*Macular Degeneration/drug therapy/diagnosis

@article {pmid41432509,
year = {2025},
author = {Neroeva, NV and Fursova, AZ and Faizrakhmanov, RR and Plyukhova, AA and Bobykin, EV and Gordeeva, MV and Karlova, EV and Bosov, ED and Nikiforova, AA},
title = {[Use of faricimab in neovascular age-related macular degeneration and diabetic macular edema in Russia. Results of the FARWATER retrospective study].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {6},
pages = {82-91},
doi = {10.17116/oftalma202514106182},
pmid = {41432509},
issn = {0042-465X},
mesh = {Humans ; Male ; Female ; Russia/epidemiology ; Retrospective Studies ; *Macular Edema/drug therapy/diagnosis/etiology/physiopathology ; Visual Acuity/drug effects ; *Diabetic Retinopathy/drug therapy/diagnosis/complications/physiopathology ; Aged ; Treatment Outcome ; Angiogenesis Inhibitors/administration & dosage ; Intravitreal Injections ; Middle Aged ; Tomography, Optical Coherence/methods ; *Wet Macular Degeneration/drug therapy/diagnosis ; Antibodies, Bispecific ; },
abstract = {UNLABELLED: Despite the positive outcomes of anti-VEGF therapy, neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) remain major medical and social challenges, and optimization of their treatment is an urgent need.

PURPOSE: This study evaluated the effectiveness of Vabysmo (faricimab) in the treatment of patients with nAMD and DME in real-world clinical practice in Russia.

MATERIAL AND METHODS: A multicenter retrospective analysis was conducted based on the medical records of 328 patients (370 eyes) with nAMD and 87 patients (112 eyes) with DME (both treatment-naïve and previously treated with anti-VEGF agents) who received faricimab from July 2023 to February 2025. The following primary effectiveness indicators were assessed: changes in visual acuity (VA) and central retinal thickness (CRT) after the first four faricimab injections. Secondary outcome indicators included changes in VA, CRT, and selected disease biomarkers at 6, 12, and 18 months of treatment, as well as injection intervals during the maintenance phase.

RESULTS: After the first four consecutive faricimab injections, VA improved by 8.1 ETDRS letters (p<0.05) in the nAMD group and by 12.8 ETDRS letters (p<0.05) in the DME group. CRT decreased by 103.3 μm (p<0.05) and 177.4 μm (p<0.05), respectively. These improvements remained stable during further follow-up (8.78±4.51 months in the nAMD group and 10.48±5.24 months in the DME group, up to a maximum of 19 months in both groups). The proportion of patients who achieved injection intervals of ≥12 weeks was 27.9% in the nAMD group and 38.5% in the DME group.

CONCLUSION: Faricimab demonstrated high clinical effectiveness in real-world settings in patients with nAMD and DME, with the potential to reduce the treatment burden for patients and the healthcare system.},
}

Humans
Male
Female
Russia/epidemiology
Retrospective Studies
*Macular Edema/drug therapy/diagnosis/etiology/physiopathology
Visual Acuity/drug effects
*Diabetic Retinopathy/drug therapy/diagnosis/complications/physiopathology
Aged
Treatment Outcome
Angiogenesis Inhibitors/administration & dosage
Intravitreal Injections
Middle Aged
Tomography, Optical Coherence/methods
*Wet Macular Degeneration/drug therapy/diagnosis
Antibodies, Bispecific

@article {pmid41432505,
year = {2025},
author = {Yusef, Y and Avetisov, KS and Khalatyan, AS and Shishparenok, AN and Blinova, VG and Gladilina, YA and Zhdanov, DD},
title = {[Monocyte telomere length as a novel biomarker of macular atrophy and response to anti-VEGF therapy in age-related macular degeneration].},
journal = {Vestnik oftalmologii},
volume = {141},
number = {6},
pages = {52-61},
doi = {10.17116/oftalma202514106152},
pmid = {41432505},
issn = {0042-465X},
mesh = {Humans ; Male ; Female ; Aged ; Tomography, Optical Coherence/methods ; *Monocytes/metabolism/pathology ; *Angiogenesis Inhibitors/administration & dosage ; *Macular Degeneration/diagnosis/drug therapy ; Visual Acuity ; *Telomere/genetics ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Biomarkers ; *Macula Lutea/pathology/diagnostic imaging ; Treatment Outcome ; *Geographic Atrophy/diagnosis/drug therapy ; },
abstract = {UNLABELLED: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the elderly. Monocyte telomere length is proposed as a marker of cellular senescence in this condition.

PURPOSE: This study investigated the association between monocyte telomere length and retinal parameters in different forms of AMD, as well as in patients receiving antiangiogenic therapy.

MATERIAL AND METHODS: Monocyte telomere length was measured in 84 patients (mean age 79±9 years) divided into four groups: non-exudative AMD with geographic atrophy (neAMD-GA), neovascular AMD (nAMD) with macular atrophy (nAMD-MA), nAMD without MA, and controls. Monocytes were isolated using immunomagnetic separation, and telomere length was determined by quantitative PCR (qPCR). Retinal parameters were assessed via optical coherence tomography (OCT) of the macular region.

RESULTS: Significant telomere shortening was observed in AMD compared to the controls (p<0.05). In the nAMD-MA group, telomere length correlated positively with best-corrected visual acuity (BCVA) after treatment (rs=0.661; p=0.0014) and the type of atrophy (p<0.0001); shorter telomeres were associated with greater BCVA decline after therapy (rs=-0.452; p=0.0419). In nAMD without MA, telomere length correlated with reduced height of neuroepithelial detachment (NED) under anti-VEGF treatment (rs=0.50; p=0.0252). No significant associations were found in the neAMD-GA and control groups.

CONCLUSION: These findings highlight monocyte telomere length as a potential biomarker for predicting macular atrophy progression and treatment outcomes in AMD. Further research is needed to confirm these associations and to explore sex/ethnic disparities in telomere length in this disease.},
}

Humans
Male
Female
Aged
Tomography, Optical Coherence/methods
*Monocytes/metabolism/pathology
*Angiogenesis Inhibitors/administration & dosage
*Macular Degeneration/diagnosis/drug therapy
Visual Acuity
*Telomere/genetics
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Biomarkers
*Macula Lutea/pathology/diagnostic imaging
Treatment Outcome
*Geographic Atrophy/diagnosis/drug therapy

@article {pmid41430718,
year = {2025},
author = {Martins, B and Boia, R and Correia, D and Ribeiro-Rodrigues, T and Ramalho, J and Ambrósio, AF and Girão, H and Fernandes, R},
title = {Retinal pigment epithelium-derived extracellular vesicles mediate outer blood retinal barrier disruption in response to AMD-related stress.},
journal = {Cell communication and signaling : CCS},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12964-025-02587-0},
pmid = {41430718},
issn = {1478-811X},
support = {Doctoral research fellowship 2020.04811//Foundation for Science and Technology (FCT, Portugal)/ ; CIBB (Center for Innovative Biomedicine and Biotechnology) research unit (UIDB/04539/Base/2020 and UIDP/04539/Programatico/2020)//Foundation for Science and Technology (FCT, Portugal)/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss among the elderly, primarily affecting the central vision. This progressive degenerative disease is characterized by the dysregulation and degeneration of the retinal pigment epithelium (RPE), a crucial cell layer beneath the photoreceptors that maintains outer retinal homeostasis. Emerging evidence suggests that during AMD, stressed RPE cells release extracellular vesicles (EVs) carrying bioactive cargo, which may compromise the outer blood-retinal barrier (oBRB) and accelerate disease progression. This study explores the role of EVs released by RPE cells under pro-inflammatory conditions in disrupting retinal integrity.

METHODS: Highly polarized primary cultures of porcine RPE (pRPE) and porcine eyecups with the RPE exposed were treated with tumor necrosis factor (TNF), lipopolysaccharide (LPS), or EVs derived from inflamed RPE cells. Additionally, Balb/c mice were intravitreally injected with RPE-derived EVs.

RESULTS: We show that EVs secreted by the apical membrane domain of porcine RPE cells exposed to LPS or TNF impair the RPE monolayer in polarized cultures, disrupt the oBRB in ex vivo porcine eyecups, and induce retinal structural damage detected in vivo in Balb/c mice. Intravitreal injection of LPS-derived EVs triggers photoreceptor and RPE layers thinning, increases reactivity in astrocytes and Müller cells, promotes pro-inflammatory microglial activation and recruitment, particularly into the outer retina, and elevates retinal apoptosis. Mechanistically, matrix metalloproteinases (MMPs) activity mediates EV-induced RPE monolayer disruption, whereas MMPs activity inhibition mitigates these effects.

CONCLUSION: Our findings reveal a novel EV-driven mechanism contributing to retinal degeneration progression, highlighting inflammation-derived apical EVs as key players in diseases involving oBRB dysfunction. Targeting EV-mediated signaling and MMPs activity may offer therapeutic strategies for preserving retinal structure and function in inflammatory retinal diseases such as age-related macular degeneration.},
}

@article {pmid41430144,
year = {2025},
author = {Hengerer, FH and Stanzel, B and Hoyos-Chacon, J and Suarez, M and Beckers, S and Busatto, P and Badalà, F},
title = {Safety and efficacy of an extended macular vision intraocular lens (IOL) for age-related macular degeneration (AMD) in real-world settings.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-025-04515-9},
pmid = {41430144},
issn = {1471-2415},
abstract = {PURPOSE: To assess the safety and efficacy of the EyeMax Mono (SharpView Ophthalmology) extended macular vision intraocular lens (IOL), in patients with age-related macular degeneration (AMD) undergoing cataract surgery.

METHODS: This retrospective multicentre study analyzed real-world data from 196 AMD eyes (146 patients) across 15 medical centres in Europe. All eyes received the single-piece, hydrophobic acrylic, EyeMax Mono IOL. AMD severity was classified by the centre. Outcomes included intraoperative and postoperative complications and changes in corrected distance and near visual acuity (CDVA and CNVA, respectively).

RESULTS: The postoperative spherical equivalent was + 1.25 ± 1.32 D. Postoperative LogMAR CDVA improved significantly from a baseline of 0.57 ± 0.38 to 0.38 ± 0.34 (n = 191, p < 0.001), while CNVA improved from 0.49 ± 0.32 at baseline to 0.35 ± 0.27 postoperatively (n = 141, p < 0.001). 63% gained > 1 line of CDVA and 27.5% gained ≥ 3 lines. For CNVA, 41.5% gained > 1 line, and 21.8% gained ≥ 3 lines. The greatest gains occurred in intermediate AMD eyes: CDVA + 0.21 logMAR, CNVA + 0.12 logMAR. Only 2.1% of eyes lost > 1 line of CDVA or CNVA.

CONCLUSIONS: The EyeMax Mono intraocular lens (IOL) safely enhances both distant (CDVA) and near (CNVA) visual acuity in patients with age-related macular degeneration, particularly in eyes with intermediate AMD. These findings are consistent with those in the published scientific literature.},
}

@article {pmid41429947,
year = {2025},
author = {Gelir, F and Akan, T and Carmichael, OT and Bhuiyan, MS and Conrad, SA and Vanchiere, JA and Kevil, CG and Bhuiyan, MAN},
title = {Topological Feature Extraction from Multi-color Channels for Pattern Recognition: An Application to Fundus Image Analysis.},
journal = {Journal of imaging informatics in medicine},
volume = {},
number = {},
pages = {},
doi = {10.1007/s10278-025-01791-1},
pmid = {41429947},
issn = {2948-2933},
support = {P20GM121307//Foundation for the National Institutes of Health/ ; R01HL172970//Foundation for the National Institutes of Health/ ; R01HL145753//Foundation for the National Institutes of Health/ ; R01HL145753-01S1//Foundation for the National Institutes of Health/ ; R01HL145753-03S1//Foundation for the National Institutes of Health/ ; R01HL149264//Foundation for the National Institutes of Health/ ; },
abstract = {The automated analysis of medical images is crucial for early disease detection. In recent years, deep learning has become popular for medical image analysis. In this study, we employed color-based topological features with deep learning for pattern recognition. The data topology provides information about the image's shape and global features such as connectivity and holes. We used different color channels to identify changes in topological footprints by altering the image's color. We extracted topological, local binary pattern (LBP), and Gabor features and used machine learning and deep learning models for disease classification. The model's performance was tested using three open-source fundus image databases: the Asia Pacific Tele-ophthalmology Society (APTOS 2019) data, the Optic Retinal Image Database for Glaucoma Analysis (ORIGA), and the Automatic Detection Challenge on Age-Related Macular Degeneration (ICHALLENGE-AMD). We have found that topological features from different color models provide important information for disease diagnosis.},
}

@article {pmid41429246,
year = {2025},
author = {Murray, M and Schifano, F and Chiappini, S and Corkery, JM and Guirguis, A},
title = {Potential eye disorders in people with and without Type 2 diabetes mellitus exposed to GLP-1 receptor agonists; an examination of the FAERS (FDA Adverse Event reporting System) database.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2025.12.015},
pmid = {41429246},
issn = {1879-1891},
abstract = {PURPOSE: As use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) for Type 2 diabetes (T2DM) and weight management increases, emerging research identifies various adverse drug reactions. This study aimed to expand this research base, focusing on eye disorders in people with and without T2DM, a novel consideration.

DESIGN: A retrospective clinical cohort disproportionality analysis of reports made to the Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: FAERS was queried regarding selected GLP-1RAs. Python 3.11 was adopted to develop a program, quantifying reported cases between January 2017 - September 2025 (January 2022-September 2025 for tirzepatide) meeting the criteria for cases with and without T2DM. Main outcome measures Reporting Odds Ratios (RORs) >4.000 and 95% confidence intervals were calculated, with metformin and orlistat as controls.

RESULTS: Compared to metformin, semaglutide showed increased reporting of optic ischaemic neuropathy (ROR: 12.269 [0.915-1.967]), cataract (ROR: 31.879 [2.463-4.461]) and retinopathy (ROR: 5.185 [0.556-2.736]) in T2DM patients, and retinopathy (ROR: 9.424 [1.081-3.406]) and retinal haemorrhage (ROR: 10.253 [0.319-4.336]) in non-T2DM patients. Tirzepatide showed increased reporting of optic ischemic neuropathy (ROR: 4.619 [0.726-2.335]) and macular degeneration (ROR: 15.579 [0.554-4.938]) in T2DM patients and eye swelling (ROR: 6.475 [0.407-3.329]) in non-T2DM patients. Liraglutide showed increased reporting of cataract (ROR: 53.866 [2.945-5.028]), diabetic retinopathy (ROR: 18.162 [1.753-4.045]) and macular degeneration (ROR: 26.261 [1.076-5.460]) in T2DM patients and cataract (ROR: 9.628 [1.387-3.142]) and macular degeneration (ROR: 9.557 [0.110-4.405]) in non-T2DM patients.

CONCLUSIONS: These results provide a signal of increased reporting of various eye disorders with GLP-1RA use compared to metformin across T2DM and non-T2DM patient cases. Further research is required to support these findings and confirm a biological causation.},
}

@article {pmid41428610,
year = {2025},
author = {Muzi, A and Gregori, G and Mangoni, L and Mogetta, V and Chhablani, J and Fruttini, D and Fiore, T and Rizzo, C and Mariotti, C and Lupidi, M},
title = {Functional and Structural Impact of Switching to Bevacizumab in neovascular-AMD Patients Treated with Aflibercept or Ranibizumab.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251409237},
doi = {10.1177/11206721251409237},
pmid = {41428610},
issn = {1724-6016},
abstract = {PurposeTo evaluate the functional and structural outcomes in patients with neovascular age-related macular degeneration (nAMD) switched from ranibizumab or aflibercept to bevacizumab.MethodsThis retrospective study included 197 eyes of 192 patients (mean age 83 ± 6 years; 38% male). Patients previously treated with ranibizumab (n = 79) or aflibercept (n = 118) were transitioned to bevacizumab. Best-corrected visual acuity (BCVA) was recorded with ETDRS charts and converted to logMAR. Spectralis SD-OCT was used to evaluate intraretinal and subretinal fluid, presence of retinal pigment epithelium detachment (PED), PED height and central retinal thickness (CRT) at baseline and after 6 months.ResultsMean BCVA decreased from 0.4 ± 0.3 to 0.5 ± 0.4 logMAR (p = 0.048). The proportion of eyes with intraretinal or subretinal fluid rose from 27% to 69% (p = 0.017). Subgroup analysis indicated greater functional and structural worsening in younger patients and in those switched from aflibercept. Mean PED height showed a non-significant increase from 163 ± 94 to 166 ± 95 µm (p = 0.091), mean PED height showed a non-significant increase from 163 ± 94 to 166 ± 95 µm (p = 0.091). In contrast, mean CRT increased substantially from 294 ± 30 µm at baseline to 310 ± 26 at 6 months (p (p < 1 × 10[-7]).ConclusionsSwitching from ranibizumab or aflibercept to bevacizumab may lead to reduced visual function and an increase in structural-OCT markers of disease activity, including greater intraretinal/subretinal fluid, CRT and worsening PED features, particularly in younger individuals and in eyes previously treated with aflibercept.},
}

@article {pmid41427444,
year = {2025},
author = {Yi, C and Luo, C and Zhao, J and Roubeix, C and Lechner, J and Penalva, R and Yang, N and Liu, J and Wang, Q and Chakravarthy, U and Sennlaub, F and Chen, M and Xu, H},
title = {Long-term low-dose aspirin promotes laser-induced choroidal neovascularization through suppressing TSP-1 expression.},
journal = {Frontiers in cellular neuroscience},
volume = {19},
number = {},
pages = {1716229},
pmid = {41427444},
issn = {1662-5102},
abstract = {PURPOSE: To investigate the impact of low-dose, long-term aspirin use on neovascular age-related macular degeneration (nAMD).

METHODS: Adult C57BL/6J or Thbs-1[-/-] mice were treated with daily aspirin (1.25 mg/kg) for 8 weeks before being subjected to laser-induced choroidal neovascularization (CNV). The animals were left for 7-10 days with continued aspirin use before the eyes were collected for further investigations. Bone marrow-derived macrophages (BMDMs) and primary retinal pigment epithelial (RPE) cells were treated with different concentrations of aspirin (1, 10, 100 μM) for two days before being subjected to LPS+IFNγ for 16 h. The expression of cytokine genes was evaluated by qRT-PCR. The concentrations of thrombospondin-1 (TSP-1) were measured by ELISA.

RESULTS: Aspirin treatment did not affect circulating immune cell profiles in normal mice but significantly increased CD11b[+] cells in laser-induced CNV mice. The treatment significantly increased the severity of laser-induced CNV and reduced serum levels of TSP-1. In vitro aspirin treatment upregulated Tnfa and Ccl22, down-regulated Thbs-1 mRNA expression, and reduced TSP-1 production in LPS+IFNγ-treated M1 BMDMs but not RPE cells. Thbs-1[-/-] mice developed severe laser-induced CNV, which was not affected by aspirin intervention. nAMD patients had significantly lower serum levels of TSP-1 than healthy controls, although no significant difference was found between nAMD patients with and without aspirin use.

CONCLUSION: Low-dose long-term aspirin use promoted the severity of laser-induced CNV by down-regulating TSP-1. Lower serum levels of TSP-1 may be a risk factor for nAMD. The long-term ocular safety of aspirin should be validated in prospective cohorts.},
}

@article {pmid41426719,
year = {2025},
author = {Agius, D and Mamo, J and Calleja, N and Smith, AF and Carbonaro, F},
title = {Estimating the costs and quality of life impact of vision loss in the population aged 50-80 years in Malta: evidence from The Malta Eye Study.},
journal = {Frontiers in public health},
volume = {13},
number = {},
pages = {1706208},
pmid = {41426719},
issn = {2296-2565},
mesh = {Humans ; Aged ; *Quality of Life ; Aged, 80 and over ; Male ; Middle Aged ; Female ; Malta/epidemiology ; *Vision Disorders/economics/epidemiology ; *Cost of Illness ; *Health Care Costs/statistics & numerical data ; Prevalence ; },
abstract = {BACKGROUND: Visual impairment and related ocular conditions impose substantial direct, indirect, and intangible costs, encompassing healthcare expenses, productivity losses, and reduced quality of life. Despite the global relevance of visual impairment, no comprehensive cost analysis has yet been conducted in an older adult Maltese population aged 50-80 years.

METHODS: Prevalence estimates from the population-based Malta Eye Study were used to calculate indirect costs via the gross national income per capita method with disability weight assumptions. Direct medical costs for key ocular conditions, including refractive error, cataract, age-related macular degeneration, diabetic retinopathy, and glaucoma, were estimated using prevalence, hospital, and private data performance indices and relevant cost data, enabling estimation of service coverage and unmet care needs. Intangible costs were derived from quality-of-life measures using the National Eye Institute Visual Function Questionnaire-39 to calculate disability weights and years lived with disability (YLD).

RESULTS: The productivity losses from blindness and moderate-severe visual impairment among individuals aged 50-80 were estimated at €16.0 million per annum (95% CI €6.0-€43.0 million). The estimated annual direct medical costs from the main ocular causes were estimated to sum up to €53.4 million (95% CI €44.6-€67.0 million), with unmet needs amounting to €20.8 million (95% CI €15.5-€28.5 million). Cataract (56.9%) and refractive error (24.5%) accounted for the highest shares of such costs. Vision-related quality of life correlated with the severity and laterality of visual impairment. Mild unilateral visual impairment carried the highest YLD rate 2264.4 YLDs per 100,000 while uncorrected refractive error carried the highest YLD rate among the visually impairing causes (2452.7 YLDs per 100,000).

DISCUSSION: Visual impairment imposes a considerable economic and quality-of-life burden on an older adult population in Malta, driven largely by cataracts, refractive error, and productivity losses. These results emphasize the need for preventive and treatment strategies and underscore the importance of future cost-benefit and cost-effectiveness analyses to help guide eye health policy in Malta.},
}

Humans
Aged
*Quality of Life
Aged, 80 and over
Male
Middle Aged
Female
Malta/epidemiology
*Vision Disorders/economics/epidemiology
*Cost of Illness
*Health Care Costs/statistics & numerical data
Prevalence

@article {pmid41425747,
year = {2025},
author = {Helland-Hansen, BA and Sverstad, A and Petrovski, G and Larsen, SE},
title = {Dynamic Pupillary Responses in Age-Related Macular Degeneration: A Controlled Clinical Study Using High-Frequency Video-Oculography.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {4689-4707},
pmid = {41425747},
issn = {1177-5467},
abstract = {PURPOSE: To investigate whether dynamic pupillary responses differ between patients with age-related macular degeneration (AMD) and healthy controls (HC), and to evaluate their potential as functional biomarkers using high-frequency, VR-based video-oculography.

METHODS: A controlled clinical study included 17 AMD patients and 17 age-matched HCs; four AMD participants were excluded for low recording quality. Dynamic pupillary responses were recorded with the BulbiCam video-oculography system (400 Hz), which presented independent monocular light stimuli through multiple permutations of bright (300 cd/m²) and dark (5 cd/m²) conditions. Measured variables included pupil diameter, latency, peak velocity, and pupil diameter-time integral (PDTI). Each eye was tested separately, and repeated sessions were analysed for reliability (intraclass correlation coefficient, ICC), repeatability (agreement index, AI), and stability (stability index, SI). Group differences were assessed using analysis of variance (ANOVA) and receiver operating characteristic (ROC) analysis.

RESULTS: AMD eyes showed larger steady-state pupil diameter and higher PDTI than controls (p < 0.05). First peak velocity was reduced in the worst eye only, while latencies were unchanged. PDTI and diameter demonstrated high reliability and stability across repetitions, and ROC analysis confirmed effective group discrimination.

CONCLUSION: High-frequency VR pupillometry detected reproducible functional alterations in AMD, consistent with impaired macular photoreceptor input but preserved reflex transmission. PDTI and diameter serve as diagnostic (population-level) and monitoring (patient-level) biomarkers, offering a non-invasive and objective method for AMD detection and follow-up in clinical and research settings.},
}

@article {pmid41425744,
year = {2025},
author = {Johari Moghadam, MM and Montazeri, F and Feldman, S and Lee, SC and Yiu, G and Moshiri, A and Emami-Naeini, P and Moussa, K and Park, SS},
title = {Longitudinal Choriocapillaris and Retinal Vascular Flow Changes on OCTA with Progression to Advanced AMD.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {4651-4662},
pmid = {41425744},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate retinal and choriocapillaris (CC) vascular flow changes on optical coherence tomography angiography (OCTA) associated with progression of intermediate age-related macular degeneration (iAMD) to geographic atrophy (GA) or neovascular AMD (nAMD).

PATIENTS AND METHODS: This retrospective, longitudinal cohort study included 68 eyes from 50 patients with iAMD at baseline who underwent OCTA and clinical examination at baseline and at 24 months. Quantitative analysis of CC flow deficits (FDs) and superficial capillary plexus vessel density (VD) was performed at baseline and after 24 months by comparing eyes that progressed to GA or nAMD to eyes that remained stable.

RESULTS: Over 24 months, 7 eyes (10.3%) developed GA and 9 eyes (13.2%) developed nAMD, including 2 that progressed to both. Eyes that developed GA had significantly greater CC FD total area at baseline when compared with stable iAMD eyes (p=0.013) and developed significant decrease in parafoveal VD (p=0.026) and full macular VD (p=0.019) after GA onset. In contrast, eyes that developed nAMD showed no significant OCTA differences at baseline when compared to stable iAMD eyes but developed a new significant increase in CC FD total area (p=0.044) and FAZ perimeter (p=0.036) after nAMD onset (p=0.044).

CONCLUSION: In iAMD eyes progressing to GA, CC ischemia was detectable before GA onset, with subsequent retinal VD loss after GA development. In iAMD eyes progressing to nAMD, CC ischemia developed concurrent with neovascularization. OCTA-derived CC and retinal flow metrics may serve as non-invasive biomarkers to stratify iAMD eyes at risk for progression.},
}

@article {pmid41425574,
year = {2025},
author = {Li, P and Wang, Q and Yang, Y and Ding, Z},
title = {Autoimmune thyroid disease and human health: a systematic review of Mendelian randomization studies.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1689498},
pmid = {41425574},
issn = {1664-3224},
mesh = {Humans ; *Mendelian Randomization Analysis ; *Thyroiditis, Autoimmune/genetics/epidemiology ; Genetic Predisposition to Disease ; *Autoimmune Diseases/genetics ; },
abstract = {UNLABELLED: We systematically summarized current Mendelian randomization (MR) evidence on the causal relationships between autoimmune thyroid disease (AITD) and a wide range of human health outcomes. Original MR studies related to AITD published up to March 1, 2025, were retrieved from PubMed and Embase. For studies investigating the same exposure-outcome associations, meta-analyses were performed to synthesize the evidence after excluding overlapping samples where applicable. The methodological quality of the included studies was assessed using the STROBE-MR checklist. A total of 123 MR publications met the inclusion criteria. MR analyses indicated that AITD significantly increased the risk of coronary atherosclerosis, deep venous thrombosis, chronic obstructive pulmonary disease, major depression, diabetic neuropathy, carpal tunnel syndrome, neuromyelitis optica spectrum disorder, diabetic retinopathy, childhood absence epilepsy, rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, inflammatory bowel disease, crohn's disease, vitiligo, myasthenia gravis, alopecia areata, type 1 and type 2 diabetes, sarcoidosis, frozen shoulder, drug eruptions, cataract, early age-related macular degeneration, pernicious anemia, Helicobacter pylori infection, temporomandibular disorders, migraine, frailty, primary biliary cholangitis, knee osteoarthritis, gout, and osteoporosis, while decreasing the risk of lung cancer, polyneuropathies, allergic rhinitis, telomere length, and serum vitamin A levels. The included MR studies were of high methodological quality and provided robust evidence supporting the bidirectional relationships between AITD and various health outcomes. These findings emphasize the importance and necessity of preventing and managing AITD while offering new perspectives and directions for future research on its prevention and treatment.

https://www.crd.york.ac.uk/prospero/, identifier CRD42023469038.},
}

Humans
*Mendelian Randomization Analysis
*Thyroiditis, Autoimmune/genetics/epidemiology
Genetic Predisposition to Disease
*Autoimmune Diseases/genetics

@article {pmid41425305,
year = {2025},
author = {Jensen, EG and Jakobsen, TS and Schnabolk, G and Wilson, K and Rask-Pedersen, M and Jensen, N and Andersen, GR and Thiel, S and Aagaard, L and Rohrer, B and Askou, AL and Corydon, TJ},
title = {Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.},
journal = {Molecular therapy. Methods & clinical development},
volume = {33},
number = {4},
pages = {101620},
pmid = {41425305},
issn = {2329-0501},
abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of vision loss and is characterized by choroidal neovascularization (CNV). Current CNV management requires multiple treatments and lacks long-term efficiency, creating a need for better therapeutics. wAMD pathogenesis is associated with excessive activation of the complement system, contributing to retinal damage. Therefore, we generated a vector expressing the small alternative pathway-targeting nanobody, hC3Nb1, to treat wAMD. We demonstrate that hC3Nb1 is efficiently expressed and secreted by mammalian cells and shows full alternative pathway and partial classical pathway inhibition in vitro. A dual-promoter approach was used to generate a lentiviral-based vector for co-expression of hC3Nb1 and marker protein eGFP. Profound and safe hC3Nb1-expression, along with its secretion from the retinal pigment epithelium (RPE), was confirmed following subretinal injection of nanobody expressing-vector in mice. The therapeutic potential of vector-encoded hC3Nb1 was demonstrated in vitro by protecting RPE from complement-mediated stress, and in vivo by reducing laser-induced CNV sizes in a mouse model consistent with complement inhibition. For the first time, nanobodies expressed in the eye are used therapeutically, and our findings suggest that hC3Nb1-based gene therapy may be a safe and long-acting treatment for wAMD and other chorioretinal diseases with dysregulated complement activation.},
}

@article {pmid41424614,
year = {2025},
author = {Song, X and Gao, G and Ye, K and Xu, P and Wang, Y and Zhang, S and Zheng, D and Ge, J and Zhong, X},
title = {Subretinal suspensions of hiPSC-derived retinal pigment epithelium cells form functional monolayers in NOD-SCID mice facilitating treatment of advanced retinal diseases.},
journal = {Regenerative therapy},
volume = {30},
number = {},
pages = {503-514},
pmid = {41424614},
issn = {2352-3204},
abstract = {INTRODUCTION: Transplantation of human induced pluripotent stem cells derived retinal pigment epithelium (hiPSC-RPE) is regarded as one of the most promising strategies for advanced retinal degenerative diseases leading to blindness, such as age-related macular degeneration. Despite its therapeutic potential, this approach is encumbered by critical challenges, notably the survival of donor RPE cells post-transplantation and the successful reconstruction of a functional RPE layer.

METHODS: With our previously reported strategy, abundant hiPSC-RPEs were generated from human induced pluripotent stem cells. These cells were characterized in vitro by morphology, marker expression and function. Further, hiPSC-RPE cell suspensions were injected into the eyes of NOD-SCID mice. Animals were monitored by optical coherence tomography screening and color fundus imaging to evaluate the survival of hiPSC-RPEs. Polarity, maturity, integration and phagocytosis of hiPSC-RPEs were analyzed histologically.

RESULTS: hiPSC-RPE cells exhibited a cobblestone morphology with abundant microvilli and tight junctions, expressed RPE specific molecular markers, and possessed ability to phagocytize photoreceptor outer segments (POS), thereby resembling the characteristics of the native human RPE cells. Following transplantation into NOD-SCID mice, the cells survived for the 8-week testing period and formed a highly organized monolayer in regions with an intact Bruch's membrane (BM) in the host retina. The reconstructed RPE layer expressed both human-specific and RPE-specific markers with POS phagocytic function. No severe adverse effects, such as malignant tumors or infections, were observed.

CONCLUSIONS: These findings demonstrate that hiPSC-RPE suspensions can survive and form RPE monolayers with morphological and functional features analogous to those of native human RPE cells in the host retina with a healthy BM. Our study may facilitate the development of cell-based therapies for treatment of advanced retinal degenerations.},
}

@article {pmid41423015,
year = {2025},
author = {Chen, X and Zhuang, X and He, G and Li, M and Zhang, X and Pu, J and Ji, Y and Zhang, Y and Hao, X and Wen, F},
title = {Increased Choroidal Stromal Volume and Altered Choriocapillaris Perfusion in Neovascular AMD: An SS-OCTA Association Study.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105327},
doi = {10.1016/j.pdpdt.2025.105327},
pmid = {41423015},
issn = {1873-1597},
abstract = {PURPOSE: This study aimed to characterize quantitative choroidal metrics using swept-source optical coherence tomography angiography (SS-OCTA) across different stages associated with neovascular age-related macular degeneration (nAMD) and to identify structural and vascular associations.

METHODS: This cross-sectional study utilized SS-OCTA to quantify 6.0×6.0 mm² macular choriocapillaris flow density (CCFD), choroidal volume (CV), choroidal stromal volume (CSV), and choroidal vascular volume (CVV), choroidal stromal index (CSI), choroidal vascularity index (CVI) and CSV/CVV ratio. Comparisons were conducted between each pair of three groups: control eyes from healthy participants, fellow eyes and nAMD affected eyes from the same unilateral nAMD patients (fellow eyes representing a potential preclinical stage).

RESULTS: The study included 230 healthy control eyes from 116 age- and sex- matched participants, 110 unaffected fellow eyes and 104 nAMD affected eyes from 110 unilateral nAMD patients. Median CCFD was 45.33% (IQR: 4.82%) in controls, 46.50% (IQR: 2.35%) in fellow eyes and 44.41% (IQR: 6.68%) in nAMD eyes. Significant differences were found between controls and fellow eyes (Adjusted P = 0.003) and between fellow eyes and nAMD eyes (Adjusted P < 0.001). Median CSV was significantly higher in both unaffected fellow eyes (5.92 mm³, IQR: 2.67 mm³; Adjusted P = 0.006) and nAMD affected eyes (6.12 mm³, IQR: 2.71 mm³; Adjusted P = 0.012) compared to controls (5.49 mm³, IQR: 2.00 mm³). Other absolute volumes also showed significant intergroup differences: CV differed between control and fellow eyes (Adjusted P = 0.033), while CVV differed significantly only between affected and fellow eyes (Adjusted P = 0.015). In contrast, normalized compositional metrics (CSI, CVI and CSV/CVV ratio) showed no significant intergroup differences (all Adjusted P > 0.05). Multivariate regression analysis in nAMD affected eyes revealed an overall inverse correlation between CSV and CCFD, with this relationship reaching statistical significance the superior nasal, nasal, inferior temporal, inferior and inferior nasal quadrants (P < 0.05).

CONCLUSION: This cross-sectional study demonstrated an association between increased CSV and the presence of nAMD, including in high-risk fellow eyes. The inverse correlation between CSV and CCFD in nAMD eyes suggested a potential interplay between stromal expansion and microvascular compromise. These findings highlighted increased CSV as a candidate biomarker that warranted investigation in future longitudinal studies to determine its prognostic value for nAMD development.},
}

@article {pmid41422988,
year = {2025},
author = {Ghosh, S and Parua, P and Jana, K and Ghosh, SK and Ghosh, A and Debnath, B and Halder, J and Sahoo, RK and Rai, VK and Dash, P and Das, C and Kar, B and Ghosh, G and Rath, G},
title = {Recent Advances of Novel Nanoformulations Combatting Blue Light Hazards in the Retina.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {110806},
doi = {10.1016/j.exer.2025.110806},
pmid = {41422988},
issn = {1096-0007},
abstract = {Exposure to blue light significantly threatens retinal health, affecting approximately 73% of the global population. It impairs vision, lowers the quality of life, and adds to public health challenges. Its treatment is getting difficult due to chronicity, limited drug efficacy, side effects, and ocular barriers that hinder conventional drug delivery. Nanoformulations (NFs) have gained attention as adaptable drug delivery systems (DDSs), offering controlled release and customizable physicochemical characteristics. Their application in ocular therapy has shown promise for targeting both anterior and posterior segments of the eye. By accommodating a broad spectrum of therapeutic agents, these nanocarriers help address the limitations of traditional retinal drug delivery methods and offer potential in mitigating blue light-induced retinal damage. Several NFs have shown significant promise in addressing blue light hazards and the retina-related diseases through various mechanisms. Nano-based formulations offer promising strategies for protecting the retina and treating retinal diseases caused by blue light exposure. Antioxidant-loaded liposomes and hydrogels, such as those containing lutein and zeaxanthin, help reduce oxidative stress. In contrast, curcumin-loaded nanoparticles (Cur-NPs) mitigate inflammation in conditions like age-related macular degeneration (AMD) and diabetic retinopathy (DR). Polymeric NPs enable gene-specific silencing of pathogenic targets, and metallic NPs enhance photothermal therapy by selectively destroying abnormal retinal cells. These advanced delivery systems, including protective nanofilms, offer improved bioavailability, targeted delivery, and minimal side effects, making them effective tools in combating retinal damage. This review emphasizes the potential of NFs for advanced drug delivery against blue light-induced retinal hazards, highlighting pharmaceutical and pharmacological findings, recent insights, key challenges, and proposed solutions for a better future.},
}

@article {pmid41422350,
year = {2025},
author = {Zhang, C and Gilead, N and Jiang, Z and Fenner, BJ and Tan, AC and Chan, HH and Teo, KYC and Cheung, CMG},
title = {Cuticular drusen in Asian neovascular age-related macular degeneration: Clinical features and polypoidal choroidal vasculopathy association.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41422350},
issn = {1435-702X},
support = {OFLCG23 may-0032//National Medical Research Council Open Fund Large Collaborative Grant/ ; },
}

@article {pmid41421557,
year = {2025},
author = {Lai, A and Issa, M and Pereira, A and Ghafri, MA and Dollin, M and Hurley, B and Chhablani, J and Yan, P},
title = {Age-related choroidal atrophy: A systematic review of multimodal imaging, clinical features, and differentiation from other forms of macular degeneration.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.12.005},
pmid = {41421557},
issn = {1879-3304},
abstract = {We conducted a systematic review on the clinical and imaging characteristics of age-related choroidal atrophy (ARCA) that distinguish ARCA from age-related macular degeneration (AMD) and geographic atrophy (GA). Studies were included if they reported on ARCA using clinical or multimodal imaging criteria and differentiated it from AMD and GA. Extracted data included subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), inner retinal layer thicknesses, and fundus findings. Risk of bias was assessed using the Joanna Briggs Institute checklists. Narrative synthesis and descriptive statistics were performed (PROSPERO (ID: CRD420251041101)). Seven studies (n = 329 patients) met inclusion criteria. ARCA was characterized by choroidal thinning (mean SFCT: 69.8 to 96.45 µm), preserved retinal pigment epithelium (RPE) on fundus autofluorescence, scleral visibility, and fundus features including peripapillary atrophy (83.3%), tessellated fundus, and pseudodrusen. Compared to control, patients with ARCA had significantly thinner peripapillary nerve fiber layer (mean: 84.2 µm vs. 90.2 µm; p = 0.047) and reduced mean ganglion cell layer, macular internal plexiform layer and CVI. ARCA contrasts with AMD and GA by its distinct imaging features, less severe visual impairment, higher glaucoma prevalence (35.3%), and more favorable response to anti-vascular endothelial growth factor agents when choroidal neovascularization is present. ARCA is a distinct clinical entity characterized by specific choroidal and retinal findings on multimodal imaging including lower CVI, thin SFCT, preserved RPE with scleral visibility, peripapillary atrophy, and inner retinal thinning. Further studies are warranted to standardize diagnostic criteria and understand long-term outcomes of ARCA.},
}

@article {pmid41420782,
year = {2025},
author = {Lopez, J and de Carlo Forest, TE and Azargui, S and Gill, ZS and Lisker-Cervantes, A and Gnanaraj, R and Lynch, AM and Palestine, AG and Mandava, N and Mathias, MT and Manoharan, N and Grove, N and Bradley, C and Patnaik, JL},
title = {Visual functioning and geographic atrophy imaging characteristics in 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 = {41420782},
issn = {1435-702X},
support = {Research to Prevent Blindness//Research to Prevent Blindness/ ; Frederic C. Hamilton Macular Degeneration Foundation//Frederic C. Hamilton Macular Degeneration Foundation/ ; Helene and Marshall Abrahams AMD Research Fund//Helene and Marshall Abrahams AMD Research Fund/ ; UM1 TR004399/TR/NCATS NIH HHS/United States ; },
abstract = {PURPOSE: To investigate the relationship between visual functioning as measured by the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25) and geographic atrophy (GA) imaging characteristics including foveal involvement, multifocal lesions, and GA size.

METHODS: This cross-sectional cohort study included patients from the University of Colorado Age-related macular degeneration (AMD) registry, enrolled between July 2014 and May 2023, who had GA in at least one eye and completed the VFQ-25 at time of study enrollment. GA size was averaged between the two eyes for each patient. General linear modeling was used to assess the association between GA imaging characteristics with the outcome of Rasch-transformed VFQ-25 scores.

RESULTS: A total of 140 AMD patients with GA and VFQ-25 scores were included in the study. LogMAR visual acuity for the better-seeing eye of each patient was negatively associated with Rasch-transformed VFQ scores (-3.03, standard error (SE): 0.46, p < 0.0001). Foveal involvement in both eyes was significantly associated with worse Rasch-transformed scores when compared to those without foveal involvement in either eye (-1.33, SE: 0.38, p = 0.0006). Multifocal lesions in both eyes compared with unifocal lesions in both eyes had no significant difference in score (p = 0.179). GA size was significantly associated with worse VFQ-25 scores (-0.09, SE: 0.02), p < 0.0001), which did not remain significant after adjustment for LogMAR of both eyes (p = 0.137).

CONCLUSIONS: We found bilateral foveal involvement and averaged GA size were significantly associated with worse Rasch-transformed VFQ-25 scores, but these associations did not remain significant after adjustment for visual acuity. Unilateral GA was significantly associated with better scores. This study highlights the impact GA imaging characteristics and bilateral involvement have on visual functioning.

KEY MESSAGES: WHAT IS KNOWN: Geographic atrophy (GA) in age-related macular degeneration negatively impacts visual functioning, and prior studies suggest that both lesion characteristics and visual acuity contribute to patient-reported outcomes.The gold-standard for Telangiectatic capillaries (TelCaps) detection is indocyanine green angiography, which is invasive and may not be readily available in all settings.

WHAT IS KNEW: Bilateral foveal involvement and larger GA size were significantly associated with worse visual functioning as measured by Rasch-transformed VFQ-25 scores.Infrared reflectance imaging complemented by optical coherence tomography B-scans are effective in the detection and measurement of TelCaps, which appeared to be dynamic lesions that remodel over time. Patients with unilateral GA reported better visual functioning, underscoring the importance of preserving vision in the better-seeing eye.Eyes with DME and TelCaps with at least one year of follow-up ended up with persistent edema and stable or worse vision after injection therapy.},
}

@article {pmid41420177,
year = {2025},
author = {Wang, K and Tian, T and Chen, Z and He, X and Xiang, Y and Zuo, G and Cheng, S},
title = {Therapeutic potential of curcumin in ophthalmic diseases: mechanisms and clinical applications.},
journal = {Journal of translational medicine},
volume = {23},
number = {1},
pages = {1408},
pmid = {41420177},
issn = {1479-5876},
mesh = {*Curcumin/therapeutic use/pharmacology ; Humans ; *Eye Diseases/drug therapy ; Animals ; Antioxidants/therapeutic use ; Clinical Trials as Topic ; },
abstract = {Ocular diseases impacting both the front and back segments of the eye are major contributors to worldwide vision loss. Curcumin, extracted from the rhizome of Curcuma longa, is a lipophilic polyphenol whose broad pharmacologic profile, including antioxidant, anti-inflammatory, antimutagenic, antimicrobial, and antineoplastic, renders it an attractive prospect for ocular therapeutics. However, much of the existing research primarily focuses on the general mechanisms of curcumin in the human body, with a lack of comprehensive reviews specifically addressing its mechanisms in ophthalmic diseases. Therefore, this review aims to explore curcumin's therapeutic potential in ophthalmic disorders and examine its mechanisms of action in terms of its anti-inflammatory, antioxidant, anti-angiogenic, neuroprotective roles, and antibacterial effects. The influence of curcumin on a range of ocular diseases, including age-related macular degeneration, diabetic retinopathy, glaucoma, cataracts, dry eye disease, pterygium, and uveitis, was also discussed. An analysis of preclinical and clinical studies conducted over the past 5 years suggested that curcumin holds promise as a therapeutic agent for various eye disorders. Furthermore, the review addressed the challenges faced in the clinical translation of curcumin in ophthalmology, such as issues related to dosage, formulation, and long-term safety. Despite curcumin's promising efficacy in preclinical models, several hurdles remain in its clinical application, highlighting the need for further research to facilitate its broader use in ophthalmic treatment.},
}

*Curcumin/therapeutic use/pharmacology
Humans
*Eye Diseases/drug therapy
Animals
Antioxidants/therapeutic use
Clinical Trials as Topic

@article {pmid41418433,
year = {2025},
author = {Song, SY and Lee, SH and Park, JW and Lim, HK and Seo, JW and Park, DH and Cho, SS},
title = {Protective effects of a 1:1 mixture of 7,17-dihydroxy-DHA and 10,17-dihydroxy-DHA (SF) against blue light-induced retinal damages in A2E-laden ARPE-19 Cells.},
journal = {Tissue & cell},
volume = {99},
number = {},
pages = {103287},
doi = {10.1016/j.tice.2025.103287},
pmid = {41418433},
issn = {1532-3072},
abstract = {In this study, we investigated the anti-age-related macular degeneration (AMD) effects of SF, a 1:1 mixture of 7,17-dihydroxy-docosahexaenoic acid (DHA) and 10,7-dihydroxy-DHA, in human retinal pigmented epithelial (RPE) cells. Cytotoxicity in RPE cells was first confirmed, while non-toxicity was confirmed at concentrations below 2 μg/mL. Irradiation of RPE cells with bis-retinoid N-retinyl-N-retinylidene ethanolamine (A2E) and blue light resulted in a cell viability of less than 80 %, whereas SF treatment increased cell viability in a concentration-dependent manner. In addition, apoptosis induced by A2E and blue light was found to be regulated by lutein and SF. Lutein and SF treatments regulated the Bcl family, with SF showing stronger efficacy in regulating Bax and Bad expression than lutein. Furthermore, SF affected MAPKs, particularly by regulating the expression of JNK and p-38. SF may have similar effects on the expression of inflammatory proteins and pro-inflammatory cytokines at 5 μg/mL and 2 μg/mL concentrations of lutein and SF. Lastly, SF appeared to regulate the expression of Nrf2, OH-1, SOD1, and 4-HNE, which are biomarkers of oxidative and carbonyl stress. In conclusion, SF may exert its protective effects by regulating various signaling pathways in response to A2E and blue light stimulation at the cellular level.},
}

@article {pmid41417677,
year = {2025},
author = {Berco, E and Kozlov, Y and Ostrovsky, M and Tuli, R and Kin Man Lee, T and Samocha, K and Shcolnik, E and Goldfeather Ben Zaken, S and Shoham-Hazon, N},
title = {Comparative Real-World Efficacy of Anti-VEGF Agents in Neovascular AMD: A Multicenter Retrospective Study.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1-18},
doi = {10.1159/000550160},
pmid = {41417677},
issn = {1423-0267},
abstract = {INTRODUCTION: This study directly compared the real-world effectiveness of bevacizumab, aflibercept 2 mg, and ranibizumab as first-line treatments for neovascular age-related macular degeneration (nvAMD).

METHODS: Multicenter retrospective cohort of treatment-naïve nvAMD eyes managed with a treat-and-extend regimen in Israel and Canada. Primary outcomes were changes in visual acuity (VA) and central retinal thickness (CRT). Secondary outcomes included treatment burden (total injections and final maintained interval), non-response (persistent/worsening exudation or functional decline despite adequate treatment), non-extension (final interval of 4 weeks), and absence of active exudation.

RESULTS: A total of 322 eyes received bevacizumab (n=174), aflibercept (n=110), or ranibizumab (n=38) over a mean follow-up of 16.75 ± 12.66 months. Mean VA improved from 0.77 ± 0.47 to 0.60 ± 0.45 logMAR following an average of 10.5 ± 6.3 injections. Aflibercept produced greater CRT reduction (-51.94 μm; p<0.001), fewer injections (-2.35; p=0.001), longer final intervals (+2.14 weeks; p<0.001), and lower odds of non-response (aOR 0.016; p<0.001) and non-extension (aOR 0.128, p<0.001) versus bevacizumab. It showed the largest mean VA gain, just short of significance on multivariable analysis (p=0.059). Ranibizumab showed greater CRT reduction (-44.53 μm; p=0.012) and lower non-extension odds (aOR 0.079; p=0.001) than bevacizumab, but did not significantly reduce treatment burden or improve VA.

CONCLUSION: In this first real-world, head-to-head comparison, aflibercept and ranibizumab outperformed bevacizumab in key anatomic and treatment-efficiency outcomes, with aflibercept showing the most consistent advantages. These findings highlight clinically relevant differences among anti-VEGF agents and underscore the importance of real-world data to guide nvAMD management.},
}

@article {pmid41415014,
year = {2025},
author = {Selya, A},
title = {Associations between Electronic Cigarettes, Smokeless Tobacco, and Age-related Macular Degeneration in the 2017 United States National Health Interview Survey.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264251405729},
pmid = {41415014},
issn = {2474-1272},
}

@article {pmid41413355,
year = {2025},
author = {Regillo, C and Kaiser, PK and Kertes, PJ and Gillies, M and Maio-Twofoot, T and Lawrence, D and Holz, FG},
title = {TALON phase IIIb study: 64 week results of brolucizumab versus aflibercept using treat-and-extend for neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41413355},
issn = {1476-5454},
abstract = {OBJECTIVE: To compare the efficacy and safety of brolucizumab 6 mg and aflibercept 2 mg in patients with neovascular age-related macular degeneration (nAMD) using an identical 4-week adjustment Treat-and-Extend regimen.

METHODS: Patients received brolucizumab (n = 366) or aflibercept (n = 368) at Weeks 0, 4, 8 and 16, followed by 4-week interval adjustments depending on disease activity (DA) up to a maximum treatment interval of 16 weeks (q16w). After introduction of the urgent safety measure (USM), patients in either arm requiring a 4-week interval were discontinued from study treatment and moved to standard of care (SoC).

RESULTS: At Week 64, more brolucizumab patients had a last treatment interval of q16w with no DA vs aflibercept (28.4% vs 12.2%). In the brolucizumab arm, 22.4%, 26.0% and 23.2% of patients were on treatment intervals of 12, 8 and 4 weeks (on SoC after USM), respectively, compared with 23.9%, 22.0% and 41.8% in the aflibercept arm. The average change in best-corrected visual acuity (letters) from baseline at Weeks 60 and 64 was comparable (brolucizumab: +4.7; aflibercept: +4.9). Average change in central subfield thickness (µm) at Weeks 60 and 64 was -182.9 µm in the brolucizumab arm vs -167.5 µm with aflibercept. Incidence of ocular adverse events (AEs), serious ocular AEs and AEs of special interest in the brolucizumab vs aflibercept arms were 31.1% vs 27.7%, 2.7% vs 0.8%, 6.0% vs 1.6%, respectively.

CONCLUSIONS: The Week 64 results in TALON reaffirmed those reported at Week 32, demonstrating extended treatment intervals and an overall favourable benefit/risk profile for brolucizumab in patients with nAMD.},
}

@article {pmid41412389,
year = {2025},
author = {Hasbolat, H and Christensen, UC and Lund-Andersen, C},
title = {Vitreous Hemorrhage due to Posterior Vitreous Detachment: Incidence of Retinal Detachment and Spontaneous Clearance during observation.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2025.11.014},
pmid = {41412389},
issn = {1549-4713},
abstract = {PURPOSE: To investigate the natural course of vitreous hemorrhage (VH) due to posterior vitreous detachment (PVD).

DESIGN: Retrospective chart review.

SUBJECTS: Consecutive patients with vitreous hemorrhage due to presumed posterior vitreous detachment between 1/1-2017 and 31/12-2021. Patients were followed conservatively.

METHODS: Patients with first episode of VH at a large eye hospital were included retrospectively through review of medical charts. Patients with a history of proliferative diabetic retinopathy, retinal venous occlusion or wet age-related macular degeneration were excluded.

MAIN OUTCOME MEASURES: Patients were followed for a minimum of two years until one of the following outcomes occurred: spontaneous VH clearing, rhegmatogenous retinal detachment (RRD), vitrectomy for persistent VH, or referral to a medical retinal service.

RESULTS: We included 366 patients (366 eyes); mean age: 65.2 years (SD 10.8), 42.9% women. VH obscured the fundus in 295 (80.6%) eyes. VH cleared spontaneously in 227 (62%), while RRD occurred in 61 (17%). Median time to RRD was 15 days (IQR: 8; 22). The risk of retinal detachment was significantly higher in men (Hazard Ratio (HR): 2.90 [1.64-5.12], p < 0.001) compared to women. Older patients exhibited a lower risk of RRD, HR 0.27 [95% CI, 0.13-0.59], p <0.001) in the 65-73 years age group, and HR 0.25 [95% CI, 0.10-0.63], p = 0.003) in the 73-94 years age group. Spontaneous clearing was associated with the density of vitreous hemorrhage. After 60 days, only 48% of the eyes cleared spontaneously. A total of 36 eyes did not clear spontaneously, requiring vitrectomy after a median duration of 98 days [62.75; 140.75].

CONCLUSION: This study demonstrates that vitreous hemorrhage presumed secondary to PVD showed great variability but generally took several months to clear, with 62% resolving spontaneously. However, 17% developed RRD; the majority during the first three weeks. Male gender and young age increased RRD risk. These findings highlight the importance of vigilant monitoring during the early phase and indicate that individual patients' characteristics may guide management strategy. Further prospective studies are warranted to refine risk stratification and optimize management protocols in this patient population.},
}

@article {pmid41412300,
year = {2025},
author = {Holt, CA and Niedert, C and Gedtal, M and Virgili, G and Hogg, RE and Qureshi, R},
title = {Prognostic factors for AMD progression - An overview of systematic reviews.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2025.12.003},
pmid = {41412300},
issn = {1879-3304},
abstract = {Age-related macular degeneration (AMD) is a progressive and irreversible degenerative disease of the retina. Slowing progression to late AMD is the only way to prevent vision loss. Given that AMD treatments are non-curative, understanding the personal characteristics associated with progression is of critical importance for people with increased AMD risk. We conducted an overview of systematic reviews and meta-analyses (SRMAs) to assess the scope of the existing literature on prognostic factors (PFs) for AMD progression. We included all systematic reviews of PFs for the progression of AMD from early or intermediate to late. We used the Cochrane Eyes and Vision Database of Systematic Reviews (current to September 2024). We identified 64 potentially relevant studies in the database and included 17 SRMAs, which most commonly studied functional or structural ocular (10/17), lifestyle (7/17), and intervention-related factors (7/17). Across all reviews, 218 PFs were reported. We extracted 79 and grouped these into 20 distinct types of PFs across 8categories. The modifiable PFs with most evidence for slowing progression were increased dietary supplementation with antioxidants and multivitamins and reduced smoking. Most PFs were non-modifiable. Although most PFs may not be targetable, by integrating high-risk optical coherence tomography findings, monitoring relevant comorbidities, and considering individual lesion characteristics, clinicians may better predict disease trajectories and support patients in slowing progression and preserving vision. Notably, no reviews studied social determinants as potential PFs for AMD progression, representing a critical gap in the evidence base. Future reviews should investigate social, systemic, and AI-identified biomarkers to provide a more comprehensive understanding of AMD progression.},
}

@article {pmid41411005,
year = {2025},
author = {Lee, WK and Wong, TY and Chen, SJ and Sun, X and Cheung, CMG and Silva, R and Ricci, F and Zhang, X and Machewitz, T and Schulze, A and Schmidt-Ott, UM and Zhao, M and Hasanbasic, Z and Leal, S and Iida, T and , },
title = {Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy: Post Hoc Analysis of the PULSAR Randomized Clinical Trial.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2025.5098},
pmid = {41411005},
issn = {2168-6173},
abstract = {IMPORTANCE: In the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) phase 3 randomized clinical trial, treatment with aflibercept, 8 mg, demonstrated noninferior (4-letter margin) best-corrected visual acuity (BCVA) gains vs aflibercept, 2 mg, in participants with neovascular age-related macular degeneration (nAMD). This post hoc subgroup analysis evaluated clinical outcomes in participants with polypoidal choroidal vasculopathy (PCV).

OBJECTIVE: To compare the efficacy and safety of aflibercept, 8 mg vs 2 mg, monotherapy among participants with PCV in the PULSAR trial.

This was a post hoc subgroup analysis of the PULSAR randomized clinical trial. The setting included hospitals and clinics in 12 countries where indocyanine green angiography (ICGA) was performed to identify PCV. Included were a subgroup of adults with nAMD enrolled in the PULSAR trial with ICGA-confirmed PCV. Study data were analyzed from August 2020 to July 2022.

INTERVENTIONS: Participants were randomly assigned 1:1:1 to aflibercept, 8 mg, every 12 weeks or 16 weeks, or aflibercept, 2 mg, every 8 weeks, each after 3 initial monthly doses. From week 16, dosing intervals in the treatment arms receiving 8 mg every 12 weeks and every 16 weeks were shortened if predefined disease activity criteria were met at prespecified visits.

MAIN OUTCOMES AND MEASURES: Least-squares (LS) mean change in BCVA from baseline at week 48.

RESULTS: A total of 139 participants were included in this analysis. ICGA-confirmed PCV was present in 44 participants in the treatment group receiving aflibercept, 8 mg, every 12 weeks (mean [SD] age, 72.2 [8.1] years; 50% male), 41 participants receiving 8 mg every 16 weeks (mean [SD] age, 73.2 [8.7] years; 63% male), and 54 participants receiving 2 mg every 8 weeks (mean [SD] age, 72.6 [8.2] years; 69% male). Mean baseline BCVA letter score (approximate Snellen) was 56.3 (20/80), 60.1 (20/63), and 57.6 (20/80), respectively, with 41, 37, and 51 participants completing week 48 and receiving a mean (SD) of 6.1 (0.4), 5.1 (0.5), and 7.0 (0.2) injections, including 68 of 78 (87%) treated with aflibercept, 8 mg, who maintained dosing intervals of 12 weeks or longer. In the treatment arms receiving aflibercept, 8 mg, every 12 and 16 weeks and aflibercept, 2 mg, every 8 weeks, LS mean BCVA change from baseline at week 48 was +9.5, +8.4, and +9.1 letters, respectively (estimated difference, 0.40; 95% CI, -4.4 to 5.2 letters for 8 mg every 12 weeks vs 2 mg every 8 weeks; -0.7; 95% CI, -4.6 to 3.2 letters for 8 mg every 16 weeks vs 2 mg every 8 weeks), and polypoidal lesions were absent in 37%, 47%, and 38% of participants, respectively, who completed week 48.

CONCLUSIONS AND RELEVANCE: Results of this post hoc analysis of the PULSAR randomized clinical trial in participants with PCV demonstrated similar visual and anatomic outcomes with aflibercept, 8 mg vs 2 mg, as administered in this trial, supporting the use of aflibercept, 8 mg, as an alternative monotherapy for PCV.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04423718.},
}

@article {pmid41408394,
year = {2025},
author = {Giraldo-Suarez, WY and Bonilla-Escobar, FJ and Lozano-Cruz, E},
title = {Comment on: 'Photobiomodulation-induced choriocapillaris perfusion enhancement and outer retinal remodelling in intermediate age-related macular degeneration: a promising therapeutic approach with short-term results'.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41408394},
issn = {1476-5454},
}

@article {pmid41408005,
year = {2025},
author = {Kayembe-Mulumba, B and Leffondré, K and Larsen, PP and Hucteau, É and Korobelnik, JF and Delcourt, C and Delyfer, MN},
title = {Association of current Statin use with incident age-related macular degeneration: using time-varying propensity scores.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41408005},
issn = {1435-702X},
support = {Fondation Bordeaux Université//Fondation Bordeaux Université/ ; Mutuelles AXA//Mutuelles AXA/ ; Théa Pharma//Théa Pharma/ ; Macu-Life Project//Macu-Life Project/ ; },
abstract = {PURPOSE: Statins exhibit pleiotropic properties that may influence age-related macular degeneration (AMD) progression. However, since their prescription is predominant in older populations at high cardiovascular risk, a lack of robust approach to control for confounding by indication could partly explain controversial results in previous studies. We therefore analyzed the association of current statin use with incident AMD using time-varying propensity score-based inverse probability of treatment weighting (IPTW).

METHODS: Analysis of data from the ALIENOR study, a 14-year French prospective population-based cohort of 963 adults aged 73 years and older in Bordeaux, followed every 2-3 years (2006-2020), with repeated assessments of statin use through a face-to-face questionnaire. AMD status was assessed using retinal multimodal imaging every 2-3 years (2006-2020). Incident intermediate and advanced AMD were analyzed separately. Combining time-varying IPTW balancing and covariates adjustment, we fitted time-dependent Cox proportional hazards models to estimate adjusted hazard ratios (aHRs [95% confidence intervals]) for incident AMD associated with current statin use (defined as using statin within the last three years prior to the current visit).

RESULTS: Over a median follow-up of 7 years, cumulative incidence was 36% and 10% among the participants analyzed for intermediate (n = 475) and advanced (n = 692) AMD, respectively. After accounting for confounding by indication, current statin use was not associated with increased hazards of intermediate (aHR: 1.02 [0.72-1.45]) and advanced (aHR: 1.08 [0.61-1.91]) AMD. Analyses of statin subtypes (lipophilic and hydrophilic) and all lipid-lowering agents consistently yielded non-significant association with the hazards of AMD. Findings were consistent across sensitivity analyses.

CONCLUSION: These findings suggest that, after controlling for confounding by indication, statins may not substantially influence the risk of developing intermediate or advanced AMD in older adults, despite the biological plausibility.},
}

@article {pmid41407273,
year = {2025},
author = {Poudel, S and Cui, Y and Meng, T and Liang, W and Zhou, K and Cheng, R and Zhao, L and Yuan, T and Kaffash, E and Halquist, MS and Ma, JX and Xu, Q},
title = {Long-acting fenofibrate-loaded microparticles for treating retinal disorders.},
journal = {International journal of pharmaceutics},
volume = {},
number = {},
pages = {126503},
doi = {10.1016/j.ijpharm.2025.126503},
pmid = {41407273},
issn = {1873-3476},
abstract = {Age-related macular degeneration (AMD) and Diabetic retinopathy (DR) are the most common forms of retinal disorders and are the leading causes of vision loss. Traditional treatments such as anti-VEGF therapies often require repeated intravitreal injections. Up to 40 % DR/AMD patients do not adequately respond to the anti-VEGF therapies. Therefore, non-VEGF therapies with alternative mechanisms are needed to address these unmet clinical needs. Fenofibrate (an FDA-approved low-cost oral drug) is a peroxisome proliferator-activated receptor-α (PPARα) agonist. We developed large-sized fenofibrate-loaded biodegradable microparticles capable of achieving high drug loading (up to 25 wt%) and sustained in vitro release exceeding six months (larger particles that load more drug and last longer). These long-acting Feno-MP exhibited desired particle size suitable for intravitreal injection (IVT) through fine gauge needles. The lead Feno-MP-F6 maintained sustained drug levels in the retina for at least 6 months following a single intravitreal injection without obvious toxic issues in rats and rabbits. This study investigated a 6-month-long therapeutic effects of a single dose of fenofibrate-loaded microparticles (Feno-MP) via a non-VEGF, PPARα-dependent mechanism in streptozotocin (STZ)-induced diabetic rats (a DR model), Vldlr[-/-] mice (a wet-AMD model), and Abca4[-/-]/Rdh8[-/-] mice (a dry-AMD model). Comprehensive analyses revealed broad therapeutic benefits across all the three disease models. In the STZ-induced DR model, one single IVT dose of Feno-MP restored both photopic and scotopic electroretinogram (ERG) responses, decreased leukostasis, and enhanced blood-retinal barrier function over a period of 6 months. In Vldlr[-/-] mice, a wet-AMD model, Feno-MP effectively reduced both subretinal and intraretinal neovascularization and decreased retinal vascular leakage for at least 6 months. In Abca4[-/-]/Rdh8[-/-] mice, single Feno-MP treatment preserved photoreceptors, increased cone photoreceptors survival and improved mitochondrial function up to 6 months. Our study showed that Feno-MP may become a promising therapy for DR, wet-AMD and even dry-AMD with only 1-2 IVT injections/year. This work represents the approach to repurpose the oral drug fenofibrate for long-lasting intraocular delivery through a sustained release system.},
}

@article {pmid41407269,
year = {2025},
author = {Khanani, AM and Danzig, CJ and Heier, JS and Jaffe, GJ and Kaiser, PK and Lally, DR and Patel, SS and Vajzovic, L and Weng, CY and Patel, H and Clark, J and Desai, D and Luo, D and Henry, E and Holz, FG and , },
title = {Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 2-year efficacy and safety results from the GATHER2 phase 3 trial.},
journal = {Ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ophtha.2025.12.011},
pmid = {41407269},
issn = {1549-4713},
abstract = {PURPOSE: Avacincaptad pegol (ACP) is a pegylated RNA aptamer that inhibits complement C5. The efficacy and safety of ACP 2mg was investigated in GATHER2, with positive Year 1 results published. Here, 2-year results are reported.

DESIGN: Phase 3, 2-year, randomized, double-masked, sham-controlled study (NCT04435366).

PARTICIPANTS: Patients with non-center point-involving geographic atrophy (GA).

METHODS: Eligible patients were randomized 1:1 to monthly ACP 2mg (N=225) or sham (N=222) for 1 year. At Month 12, patients who received ACP 2mg and completed Year 1 were re-randomized 1:1 to monthly (EM; n=96) or every-other-month (EOM; n=93) ACP 2mg. Patients who had received monthly sham continued with sham (n=203).

MAIN OUTCOME MEASURES: To evaluate the safety and efficacy of ACP 2mg vs sham over 2 years, and to assess the effect of ACP 2mg EM or EOM dosing in Year 2.

RESULTS: Overall, 175 and 184 patients in the ACP 2mg and sham group completed the study at Year 2, respectively. At 2 years, treatment with ACP 2mg demonstrated a continued reduction in GA growth (slope) with both ACP 2mg EM and EOM vs sham. From baseline to Year 2, the mean rate of GA area growth was 4.46mm[2] (standard error [SE]: 0.25) with ACP 2mg EM and 5.18mm[2] (SE: 0.17) with sham, a difference in growth of 0.724mm[2] (95% confidence interval [CI]: 0.133,1.315; P=0.0165), representing a 14% difference. From baseline to Year 2, the mean rate of GA area growth was 4.20mm[2] (SE: 0.25) with ACP 2mg EOM, a difference in growth of 0.976mm[2] (95% CI: 0.377,1.575; nominal P=0.0015) vs sham, representing a 19% difference. Over 2 years, ocular treatment-emergent adverse events (study eye) occurred in 64.0% and 48.2% of patients with ACP 2mg (all treated) and sham, respectively. The incidence of choroidal neovascularization (study eye) was 11.6% with ACP 2mg (all treated) vs 9.0% with sham over 2 years. No events of retinal vasculitis, ischemic optic neuropathy, or serious intraocular inflammation occurred over 2 years.

CONCLUSIONS: Dosing of ACP 2mg, either EM or EOM, continued to reduce GA growth vs sham over 2 years with no new safety signals compared with Year 1.},
}

@article {pmid41406248,
year = {2025},
author = {Bartolomeo, N and Barbosa, M and Pannatier Schuetz, Y and Castro, DG and Nascimbeni, AC and Barry, MP and Ambresin, A},
title = {Pigment epithelial detachment as a biomarker for faricimab treatment outcomes in naïve neovascular age-related macular degeneration.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251400508},
doi = {10.1177/11206721251400508},
pmid = {41406248},
issn = {1724-6016},
abstract = {ObjectiveTo assess baseline pigment epithelial detachment (PED) and other OCT biomarkers for predicting response to faricimab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).DesignThis was an observational, retrospective, single-arm, monocentric cohort study.Subjects and methodsFifty-seven eyes of 51 patients with naive nAMD-associated PED and treated with faricimab were included in the study. Best-corrected visual acuity (BCVA) and OCT were performed at baseline, monthly until Month 4, and at Months 6, 9, and 12. Fluid volume dynamics and other OCT biomarkers were quantified using an AI-based tool.ResultsAt Month 12, mean BCVA increased by 4 letters (P < 0.01), mean CRT decreased by 66.2 µm (P < 0.0001), and mean maximum PED height decreased by 70.4 µm (P < 0.001). AI-based PED dynamics showed rapid and sustained reductions from 488.2 nL at baseline to 166.6 nL at Month 12 (P < 0.0001), with more profound reductions in serous versus fibrous PED volume. All AI-quantified OCT biomarkers were significantly (P < 0.0001) changed from baseline after the loading phase. OCT biomarkers, PED, and fluid dynamics during the loading phase were correlated with functional and anatomic outcomes at Month 4 and Month 12.ConclusionsFaricimab had a rapid, profound and sustained drying effect on the retinas of eyes with nAMD and PED, with marked reductions in OCT biomarkers after loading and sustained to Month 12. These improvements coincided with significant improvements in BCVA. PED height, type, and volume at baseline correlated with short- and long-term treatment outcomes.},
}

@article {pmid41406245,
year = {2025},
author = {Borrelli, E and Reibaldi, M},
title = {The importance of imaging biomarkers for predicting outcomes in neovascular AMD.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721251407415},
doi = {10.1177/11206721251407415},
pmid = {41406245},
issn = {1724-6016},
}

@article {pmid41405094,
year = {2025},
author = {Enzendorfer, ML and Mai, J and Riedl, S and Bogunovic, H and Menten, MJ and Rueckert, D and Fritsche, LG and Prevost, AT and Sivaprasad, S and Pfau, M and Scholl, HPN and Lotery, AJ and Sacu, S and Schmidt-Erfurth, U},
title = {Functional Outcomes Across High-Risk OCT-Based Phenotypes in Intermediate Age-Related Macular Degeneration-PINNACLE Study Report 11.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {54},
doi = {10.1167/iovs.66.15.54},
pmid = {41405094},
issn = {1552-5783},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Aged ; *Visual Acuity/physiology ; Male ; Female ; Phenotype ; *Macular Degeneration/physiopathology/diagnosis ; Visual Fields/physiology ; Aged, 80 and over ; Retinal Drusen/physiopathology ; Visual Field Tests ; Middle Aged ; *Retina/physiopathology/pathology ; Angiogenesis Inhibitors/therapeutic use ; },
abstract = {PURPOSE: To evaluate the association between structural optical coherence tomography (OCT) biomarkers and functional outcomes in intermediate age-related macular degeneration (iAMD) and to investigate whether stratifying eyes by OCT-based biomarkers identifies phenotypes of iAMD with impaired visual function.

METHODS: The baseline cohort of the PINNACLE trial underwent OCT imaging, microperimetry, best-corrected visual acuity (BCVA), and low-luminance visual acuity (LLVA) testing. OCT volumes were assessed for the presence of different morphologic features. Drusen volume and outer nuclear layer (ONL) and ellipsoid zone (EZ) thickness were quantified. Linear mixed-effect models evaluated associations between each feature and functional outcomes, including a stratification into phenotypes based on significant OCT morphology with each eye assigned to a single group.

RESULTS: This analysis included 247 eyes of 190 patients (mean age, 74.2 ± 7.4 years). The presence of subretinal drusenoid deposits (SDDs) and markers of retinal atrophy were significant contributors to lower mean retinal sensitivity (P < 0.05). Also, higher drusen volume and lower ONL and EZ thickness were associated with lower sensitivity. Significant changes in BCVA, LLVA, and low-luminance deficits (LLDs) were associated with increasing drusen volume and the presence of hyperreflective foci (HRF). Significant functional differences were found between individual phenotypic groups, especially highlighting functional deficit in eyes with signs of early atrophy.

CONCLUSIONS: Integrating comprehensive analyses of structural OCT biomarkers with functional assessments revealed distinct phenotypic subtypes of iAMD that are associated with significant functional deficits. Particularly, early atrophy markers should be considered for patient selection and risk assessment in clinical trials and routine practice.},
}

Humans
*Tomography, Optical Coherence/methods
Aged
*Visual Acuity/physiology
Male
Female
Phenotype
*Macular Degeneration/physiopathology/diagnosis
Visual Fields/physiology
Aged, 80 and over
Retinal Drusen/physiopathology
Visual Field Tests
Middle Aged
*Retina/physiopathology/pathology
Angiogenesis Inhibitors/therapeutic use

@article {pmid41405093,
year = {2025},
author = {Suzuki, T and Terao, R and Nagahara, M and Hayashi, K and Azuma, K and Shinzawa, K and Moriwaki, K and Shiraya, T and Honjo, M and Ueta, T},
title = {iPLA2β Protects Retinal Pigment Epithelium From Ferroptosis in a Sodium Iodate-Induced Model of Dry AMD.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {55},
doi = {10.1167/iovs.66.15.55},
pmid = {41405093},
issn = {1552-5783},
mesh = {Animals ; *Ferroptosis/physiology/drug effects ; *Retinal Pigment Epithelium/pathology/metabolism/drug effects ; Iodates/toxicity ; Disease Models, Animal ; Mice ; Mice, Knockout ; Electroretinography ; *Group VI Phospholipases A2/physiology ; Mice, Inbred C57BL ; Oxidative Stress ; *Macular Degeneration/chemically induced/metabolism ; Blotting, Western ; Real-Time Polymerase Chain Reaction ; Lipid Peroxidation ; },
abstract = {PURPOSE: Ferroptosis, characterized by lipid peroxidation, has been implicated in retinal pigment epithelium (RPE) degeneration in dry age-related macular degeneration (AMD). This study aimed to investigate the role of calcium-independent phospholipase A2 group VI (iPLA2β) in protecting RPE cells from oxidative stress using a sodium iodate (NaIO3)-induced dry AMD model.

METHODS: The iPLA2β knockout (KO) and wild-type (WT) mice were subjected to NaIO3 administration. Retinal structure and function were evaluated by histology and electroretinography. The involvement of ferroptosis was assessed by quantitative real-time polymerase chain reaction (qPCR) and Western blotting. Pharmacological intervention experiments used ferrostatin-1, α-tocopherol, and necrostatin-1s to evaluate protective effects. Western blotting was performed for RIP3 phosphorylation, and RIP3 KO mice were used to further assess necroptosis involvement.

RESULTS: The iPLA2β KO mice exhibited normal retinal morphology and function under baseline conditions. NaIO3 exposure caused pronounced RPE and photoreceptor degeneration, a characteristic downregulation of genes responsive to ferroptotic stress, elevated lipid peroxidation, and impaired visual function, which were markedly rescued by ferrostatin-1 and α-tocopherol, and partially by necrostatin-1s. NaIO3 did not induce RIP3 phosphorylation, and necrostatin-1s appeared to exert antioxidative effects. RIP3 KO mice developed severe RPE degeneration after NaIO3 exposure, significantly attenuated by necrostatin-1s. These findings indicate that lipid peroxidation-mediated ferroptosis, rather than necroptosis, is the primary mechanism of NaIO3-induced retinal degeneration, particularly at low doses of NaIO3.

CONCLUSIONS: The iPLA2β functions as a key suppressor of lipid peroxidation-mediated RPE degeneration in the NaIO3 model. Targeting ferroptosis-particularly via iPLA2β-may represent a potential therapeutic approach for protecting the RPE from oxidative stress-induced injury in dry AMD, although further validation in human tissues will be necessary.},
}

Animals
*Ferroptosis/physiology/drug effects
*Retinal Pigment Epithelium/pathology/metabolism/drug effects
Iodates/toxicity
Disease Models, Animal
Mice
Mice, Knockout
Electroretinography
*Group VI Phospholipases A2/physiology
Mice, Inbred C57BL
Oxidative Stress
*Macular Degeneration/chemically induced/metabolism
Blotting, Western
Real-Time Polymerase Chain Reaction
Lipid Peroxidation

@article {pmid41404584,
year = {2025},
author = {Che, S and Ma, Y and Cao, J},
title = {Association between serum carotenoid concentrations and risk of major age-related eye diseases among middle-aged and older adults.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1596799},
pmid = {41404584},
issn = {2296-858X},
abstract = {BACKGROUND: Age-related eye diseases are the main causes of progressive and irreversible vision loss in aging populations worldwide. Carotenoids, as a group of common natural antioxidants, can suppress free radicals produced by complex physiological reactions, thereby protecting the eyes from the effects of oxidative stress, cell apoptosis, and mitochondrial dysfunction. The present study aims to explore the association between serum carotenoid concentrations and risk of major age-related eye diseases among middle-aged and older adults in the United States.

METHODS: This study involved 1,478 participants aged ≥50 years from the 2005-2006 cycles of the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of prevalence of cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in relation to serum carotenoid concentrations.

RESULTS: Compared to participants in the first quartile, those in highest quartile of serum α-carotene (OR: 0.37; 95% CI: 0.21-0.64), β-carotene (OR: 0.57; 95% CI: 0.33-0.95), lutein/zeaxanthin (OR: 0.45; 95% CI: 0.27-0.76), and total carotenoid (OR: 0.58; 95% CI: 0.35-0.97) were negatively associated with risk of cataract; those in highest quartile of serum β-carotene (OR: 0.30; 95% CI: 0.11-0.77) and β-cryptoxanthin (OR: 0.28; 95% CI: 0.12-0.68) were negatively associated with risk of diabetic retinopathy; and those in highest quartile of lycopene (OR: 0.37; 95% CI: 0.18-0.78) was negatively associated with risk of AMD. In addition, subgroup analysis results indicated that participants in highest quartile of serum α-carotene (OR: 0.16; 95% CI: 0.08-0.32), β-carotene (OR: 0.40; 95% CI: 0.21-0.75), lycopene (OR: 0.46; 95% CI: 0.24-0.87), lutein/zeaxanthin (OR: 0.45; 95% CI: 0.25-0.84), and total carotenoid (OR: 0.41; 95% CI: 0.22-0.77) concentrations were negatively associated with risk of any ocular disease among female participants. By contrast, no associations were observed among male participants.

CONCLUSION: Our study demonstrated that higher serum concentrations of carotenoids were negatively associated with the risk of age-related eye diseases, particularly among middle-aged and older female participants.},
}

@article {pmid41404347,
year = {2025},
author = {Attia, M and Pavlovic, T and Muliawan, A and Tuya, F and Mihalatos, M and Iwanicki, M and Kang-Mieler, J},
title = {Therapeutic potential of taurine in a pigmented rat model of age-related macular degeneration.},
journal = {Frontiers in ophthalmology},
volume = {5},
number = {},
pages = {1701761},
pmid = {41404347},
issn = {2674-0826},
abstract = {PURPOSE: To investigate the potential protective effects of taurine supplementation against retinal degeneration in an animal model of mild dry age-related macular degeneration (AMD).

METHODS: To test the effects of a taurine supplement in mild dry AMD, sodium iodate (NaIO3)-induced retinal degeneration model was used. Two administration methods, intraperitoneal (IP) and intravenous (IV), were used to deliver NaIO3 in pigmented Long Evans rats to generate mild and severe dry AMD, respectively. Structural abnormalities were evaluated in vivo using near-infrared (IR) reflectance fundus imaging and optical coherence tomography (OCT). Using the slow progressive mild AMD model, we investigated the neuroprotective effects of oral taurine supplementation (1.5% w/v in drinking water) against NaIO3-induced retinal degeneration over 20 weeks. In addition, a human Retinal Pigment Epithelium (RPE, hTERT-RPE1) cell culture model was used to directly assess taurine's ability to protect against NaIO3-related oxidative stress.

RESULTS: The high-dose IV model (80 mg/kg) exhibited extensive and severe retinal damage, with ONL thinning by 64.2% and total retinal thickness (TRT) by 47.6%, predominantly in the peripapillary region. In contrast, the lower-dose IP model (50 mg/kg) displayed milder, more gradual deterioration (outer nuclear layer (ONL) thinning by 19.4% and TRT by 11.5%). Oral taurine supplementation significantly preserved ONL and TRT in vivo and supported RPE-1 cell survival, proliferation, and motility, under NaIO3 conditions.

CONCLUSION: Taurine supplementation provided significant structural protection against NaIO3-induced damage both in vivo and in cell culture, demonstrating its potential as a therapeutic candidate for mitigating mild dry AMD progression.},
}

@article {pmid41402601,
year = {2025},
author = {Sadeghi, E and Chhablani, J},
title = {Response to: 'Comment on 'Correlation of retino-choroidal thickness and vascular metrics with drusen volume as a severity marker of age-related macular degeneration".},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41402601},
issn = {1476-5454},
}

@article {pmid41402599,
year = {2025},
author = {Zhou, WD and Dong, L and Yang, YH and Zhao, HQ and Zhang, RH and Li, YT and Yu, CY and Li, HY and Wu, HT and Shi, XH and Shao, L and Wei, WB},
title = {Retinal single-cell blood velocity in eyes with varied axial length using adaptive optics scanning laser ophthalmoscopy.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41402599},
issn = {1476-5454},
abstract = {BACKGROUND: To investigate the hemodynamic changes in the retinal vasculature of the macular region in eyes with axial myopia.

METHODS: Individuals with varying axial lengths were included in this study. Inclusion criteria was the absence of any ocular or systemic diseases. A commercial adaptive optics scanning laser ophthalmoscopy was used to capture images of retinal vessels within the 5°-10° areas above and below the foveal centre. This system provided noninvasive imaging of single blood cells and automatically calculated blood velocity while detecting the flow direction. Vessels were classified based on their diameter.

RESULTS: The study included 90 patients (180 eyes; 35 (38.9%) men) with a mean age of 34.3 ± 12.2 years (range: 19-62 years) and a mean axial length of 25.8 ± 1.9 mm (range: 21.4-30.6 mm). The mean blood velocity in retinal arteries and veins was 35.2 ± 11.4 mm/s and 34.9 ± 13.2 mm/s, respectively. Single-cell blood velocity was significantly increased with longer axial length in large retinal arteries (diamater≥100μm) (B = 2.73; β = 0.32; P = 0.01); and medium retinal arteries (diameter<100μm) (B = 1.83; β = 0.27; P = 0.003). Correspondingly, the blood velocity of medium retinal arteries in the myopic group was significantly higher than that in the non-myopic group (t = 3.37; P = 0.001). Single-cell blood velocity was significantly increased with longer axial length in medium retinal veins (diameter <110 μm) (B = 2.0; β = 0.3; P = 0.016). Correspondingly, the blood velocity of medium retinal veins in the myopic group was significantly higher than that in the non-myopic group (t = 2.25; P = 0.03).

CONCLUSIONS: Single-cell retinal blood velocity was significantly increased with longer axial length. These findings suggest that the hemodynamic changes observed in axial myopia, including higher arterial and venous blood velocities, may provide a potential explanation for the lower prevalence of diabetic retinopathy, age-related macular degeneration, and branch retinal vein occlusion reported in previous epidemiological studies.},
}

@article {pmid41400582,
year = {2025},
author = {Ma, H and Li, S and Le, Y and Stanford, D and Freeman, WM and Ding, XQ},
title = {Single Cell RNAseq Analysis of Thyroid Hormone Effects on Retinal Glial Cells.},
journal = {Aging and disease},
volume = {},
number = {},
pages = {},
doi = {10.14336/AD.2025.1221},
pmid = {41400582},
issn = {2152-5250},
abstract = {Thyroid hormone (TH) signaling regulates cellular metabolism and stress response in the retina. Increased TH levels in circulation are associated with a higher incidence of age-related macular degeneration. Furthermore, stimulation of TH signaling induces retinal degeneration in mice, which is accompanied by the activation of retinal glial cells. Here, we investigated the transcriptional changes induced by triiodothyronine (T3) in retinal glial cells using single-cell RNA sequencing (scRNAseq) and bioinformatic analyses. One-month-old C57BL/6 mice were given T3 (20 μg/ml in drinking water) for four weeks, after which their retinal cells were collected to assess viability and undergo scRNAseq. The resulting data were analyzed using the Seurat package, visualized by the Loupe Browser, and Ingenuity Pathway Analysis. Analyses of differentially expressed genes (DEGs) in Müller cells, astrocytes, and microglia revealed significant enrichment in pathways associated with stress, immune response, and degeneration. Müller cells exhibited upregulation of mitochondrial dysfunction, acute-phase response, and sirtuin signaling pathways. Astrocytes displayed downregulation of synaptogenesis, neurovascular coupling, cAMP response elements, and calcium signaling. Microglia showed upregulation of coordinated lysosomal expression and regulation signaling, systemic lupus erythematosus in T cells, and multiple sclerosis signaling, and downregulation of actin-binding Rho activating signaling, retinoic acid receptor activation signaling, and IL-17 signaling. The distinct and overlapping transcriptional responses suggest that each retinal glial cell type plays a specific and coordinated role in adapting to stress. This study offers new insights into TH-induced retinal stress and degeneration at the transcriptional and pathway-level responses of retinal glial cells.},
}

@article {pmid41399815,
year = {2025},
author = {Leozappa, M and Mavilio, A and Durante, G and Piccinni, L and Miggiano, A},
title = {SING IMT telescopic intraocular lens implantation in a patient with inverse retinitis pigmentosa: A case report.},
journal = {American journal of ophthalmology case reports},
volume = {40},
number = {},
pages = {102479},
pmid = {41399815},
issn = {2451-9936},
abstract = {PURPOSE: To report the off-label use of the SING IMT telescopic intraocular lens (IOL) (Samsara Vision) in a patient with inverse retinitis pigmentosa (RP) and cataracts, evaluating its impact on visual acuity and functional outcomes.

OBSERVATIONS: A 77-year-old female with inverse RP, bilateral cataracts, hypertension, and hypercholesterolemia presented with hand motion visual acuity (≥2.3 LogMAR) bilaterally, assessed using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart at 2 meters. An external telescopic simulator improved visual acuity to 6 letters (1.58 LogMAR) in the left eye. Preoperative assessments, including optical coherence tomography, fundus autofluorescence, and electrophysiological testing, confirmed central macular degeneration and supported left-eye SING IMT implantation. Phacoemulsification with SING IMT implantation was performed, followed by a visual rehabilitation program. By 6 months, visual acuity reached 6 ETDRS letters (1.58 LogMAR) at 3 meters. Functional improvements included reading, writing, sewing, and television viewing, with enhanced autonomy and mood. Mild corneal edema resolved within 1 week, and no posterior capsular opacification or cystoid macular edema occurred during 8 months of follow-up.

CONCLUSION AND IMPORTANCE: This case reporting use of the SING IMT in inverse RP demonstrates its potential to improve vision and quality of life in patients with central vision loss from retinal dystrophies, surpassing typical cataract surgery outcomes. The 2.5x magnification and structured rehabilitation were key to functional gains. Larger studies are needed to validate efficacy and refine patient selection.},
}

@article {pmid41399598,
year = {2025},
author = {Flindris, K and Gorgoli, K and Koumpoulis, I},
title = {A Case Series of Bacillary Layer Detachment (BALAD) in Neovascular Age-Related Macular Degeneration (nAMD): A Novel Optical Coherence Tomography (OCT) Biomarker.},
journal = {Cureus},
volume = {17},
number = {11},
pages = {e96819},
pmid = {41399598},
issn = {2168-8184},
abstract = {Bacillary layer detachment (BALAD) is a newly recognized optical coherence tomography (OCT) finding, defined as a split at the photoreceptor inner segment (myoid zone) resulting in a dome-shaped intraretinal fluid cavity. BALAD has been reported in various chorioretinal diseases and may serve as a novel structural OCT biomarker of severe exudation. We present a case series of BALAD in neovascular age-related macular degeneration (nAMD) to characterize its multimodal imaging features and discuss its diagnostic and prognostic significance. Three patients with active nAMD exhibited BALAD on spectral-domain OCT. In each instance, OCT cross-sections showed a sharply demarcated hyporeflective intraretinal cavity beneath an intact external limiting membrane (ELM) and above the ellipsoid zone (EZ). OCT angiography (OCTA) revealed an underlying high-flow choroidal neovascular network corresponding to the BALAD in all cases. All three patients initially had significant visual impairment. Two patients were treated with serial intravitreal anti-vascular endothelial growth factor (VEGF) injections, resulting in rapid resolution of the BALAD cavity, reabsorption of subretinal and intraretinal fluid, and marked improvement in best-corrected visual acuity (e.g., from 20/400 to 20/40). The third patient, who declined treatment, developed persistent BALAD with progressive subfoveal fibrosis and no visual recovery. BALAD in nAMD indicates an aggressive disease phenotype with intense outer retinal fluid accumulation and photoreceptor layer schisis. Prompt anti-VEGF therapy was associated with anatomical recovery and vision improvement in the treated cases. Recognizing BALAD on OCT and OCTA is clinically important, as it differentiates intraretinal from subretinal pathology and underscores the need for early, aggressive treatment to mitigate irreversible retinal damage in nAMD.},
}

@article {pmid41398938,
year = {2025},
author = {Kose, H and Ozkan, B and Kanli, A and Karabas, LV and Akpinar, G and Kasap, M and Sumer, F},
title = {Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.},
journal = {BMC geriatrics},
volume = {25},
number = {1},
pages = {1019},
pmid = {41398938},
issn = {1471-2318},
mesh = {Humans ; *Proteomics/methods ; Female ; Male ; Aged ; Prospective Studies ; *Macular Degeneration/metabolism/diagnosis ; *Vitreous Body/metabolism/chemistry ; Case-Control Studies ; *Eye Proteins/metabolism ; Aged, 80 and over ; Middle Aged ; Biomarkers/metabolism ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) represents one of the most common causes of permanent vision impairment in individuals over 50 years of age.

METHODS: This study aims to characterize AMD using proteomic analysis to enhance diagnosis and treatment strategies. In a prospective case-control clinical trial, vitreous fluids (VF) from thirteen AMD patients were collected during surgery and analyzed by 2DE-based MALDI TOF-TOF MS/MS. PANTHER and STRING analyses were performed to investigate the biological relationships between the identified proteins and to determine relevant cellular pathways.

RESULTS: A total of 11 proteins were differentially regulated between AMD patients and healthy controls. Among them, Apolipoprotein E was significantly up-regulated (↑3-fold), while ten proteins, including alpha-crystallin A chain (↓779-fold), beta-crystallin B2 (↓232-fold), and haptoglobin (↓15-fold), were markedly down-regulated. These quantitative differences underscore the critical role of lipid metabolism, oxidative stress response, and inflammation in AMD pathogenesis.

CONCLUSION: The identified proteins are related to biological regulation, retinal protection, and regulation of inflammation and angiogenesis processes. The up-regulation of Apolipoprotein E highlights its involvement in lipid metabolism and inflammatory modulation, while the sharp down-regulation of crystallin family proteins suggests compromised retinal protection against oxidative stress and apoptosis. These protein alterations provide new insights into AMD pathogenesis and may serve as potential biomarkers for early diagnosis and novel therapeutic targets in managing the disease.},
}

Humans
*Proteomics/methods
Female
Male
Aged
Prospective Studies
*Macular Degeneration/metabolism/diagnosis
*Vitreous Body/metabolism/chemistry
Case-Control Studies
*Eye Proteins/metabolism
Aged, 80 and over
Middle Aged
Biomarkers/metabolism

@article {pmid41398318,
year = {2025},
author = {Keshet, Y and Ngo, WK and Salcedo-Ledesma, A and Walia, JJ and Spaide, RF},
title = {Quantitative assessment of hyperreflective dots in the outer nuclear layer over neovascular lesion components.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41398318},
issn = {1476-5454},
abstract = {OBJECTIVES: To evaluate the outer nuclear layer for hyperreflective dots (HRD), a proposed imaging correlate of retinal microglia, in eyes with neovascular age-related macular degeneration (nAMD).

METHODS: High-resolution optical coherence tomography (OCT) of eyes with nAMD was evaluated with the aid of a custom ImageJ plugin that automatically identified HRD and plotted them on the corresponding near infrared (IR) fundus image. Areas of subretinal fluid (SRF), double layer sign (DLS), and the area of neovascularisation as imaged by OCT angiography (A) were mapped to the near-IR image. The number of HRD overlying these regions was tabulated.

RESULTS: There were 38 eyes of 38 patients. SRF was present in 23 eyes, there was a median 8.5 HRD /mm[2] over this area. DLS was present in all eyes and with a median of 6.5 HRD/mm[2] over this area. Neovascularisation was detectable using OCTA with a median of 6.8 HRD/mm[2]. The density of HRD/mm[2] was not significantly different over areas of DLS with fluid compared to areas of DLS without SRF (P = 0.22). The median HRD/mm[2] for uninvolved areas of the retina was 0.7, a difference that was significantly less than over areas of SRF, DLS, and OCTA detected neovascularisation (P < 0.001 for all comparisons).

CONCLUSIONS: There is an aggregation of HRD in the outer retina over lesion components of nAMD. These HRD may be present in response to SRF, but their existence over regions of the neovascular lesion without SRF suggests that additional factors are involved in their recruitment.},
}

@article {pmid41398283,
year = {2025},
author = {Antonietti, M and Mercado, C and Smiddy, WE and Schwartz, SG},
title = {Central retinal vein occlusion following intravitreal injections: a case series highlighting multifactorial risk.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-025-00781-3},
pmid = {41398283},
issn = {2056-9920},
support = {GR004596-1//Research to Prevent Blindness Unrestricted Grant/ ; },
}

@article {pmid41397442,
year = {2025},
author = {Li, N and Hong, R and You, H and Xu, F and Zhang, Q and Lin, Y and Su, Y and Lan, D and Jin, L and She, J},
title = {DELP Treatment on Vision and Retinal Microcirculation in Patients With Acute Ischemic Stroke: Report of Five Cases and Literature Review.},
journal = {Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy},
volume = {},
number = {},
pages = {},
doi = {10.1002/1744-9987.70102},
pmid = {41397442},
issn = {1744-9987},
support = {2023YFC3604500//National Key Research and Development Program of China/ ; 2023YFC3604505//National Key Research and Development Program of China/ ; 22Y31900200//Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; 22Y31900203//Science and Technology Innovation Plan Of Shanghai Science and Technology Commission/ ; Z155080000004//National Clinical Key Specialty Project Foundation/ ; SHDC22023304//Shanghai Municipal Hospital Development Center/ ; 82230084//National Natural Science Foundation of China/ ; 82172545//National Natural Science Foundation of China/ ; 82201404//National Natural Science Foundation of China/ ; //Shanghai Blue Cross Hospital Co., Ltd. and Shanghai Tongji University Educationg Development Foundation/ ; 2024QN05//Shanghai Jing'an District Science and Technology Commission and Jing'an District Health Commission/ ; },
abstract = {BACKGROUND: The delipid extracorporeal lipoprotein filter from plasma (DELP) treatment can effectively reduce blood lipid, increase blood flow, and improve neurological deficits in patients with acute ischemic stroke (AIS). However, its effect on vision and retinal microcirculation in stroke patients has never been reported.

METHODS: Between November 2023 and June 2024, five patients underwent DELP treatment as a routine adjuvant therapy for AIS. Detailed ophthalmological examinations, including best corrected visual acuity (BCVA) and optical coherence tomography angiography (OCTA), were performed on them one day prior to and 1-3 days following the DELP treatment.

RESULTS: Among the ten eyes examined, six had diabetic retinopathy (DR), two had dry age-related macular degeneration (dAMD), one had idiopathic epiretinal membrane (iERM), and one was normal. Surprisingly, after DELP treatment, the BCVA improved by 0.2LogMAR in six eyes, 0.1LogMAR in three eyes, and remained unchanged in one eye. The vessel density (VD) in the fovea increased in six eyes, remained unchanged in three eyes, and decreased in one eye. The non-perfusion area (NPA) in the superficial capillary plexus (SCP) decreased in six eyes, remained unchanged in two eyes, and increased in two eyes. The NPA in the deep capillary plexus (DCP) decreased in eight eyes and remained unchanged in two eyes. A small amount of bleeding occurred in Patient 3's right eye, and no other adverse events were observed post-treatment.

CONCLUSIONS: In this case series, the DELP treatment showed a potentially significant therapeutic effect on the BCVA and retinal microcirculation in AIS patients with good safety and provided a rationale for further investigation. At the same time, this treatment may provide an effective option for the treatment of eye diseases such as DR, iERM, and AMD.},
}

@article {pmid41396593,
year = {2025},
author = {Zhong, Y and Qin, Y},
title = {Frailty-Driven Risk Stratification in Age-Related Ophthalmic Diseases: Thresholds, Precision Screening, and Mendelian Randomization Insights.},
journal = {Translational vision science & technology},
volume = {14},
number = {12},
pages = {17},
doi = {10.1167/tvst.14.12.17},
pmid = {41396593},
issn = {2164-2591},
mesh = {Humans ; *Mendelian Randomization Analysis/methods ; Male ; Aged ; *Frailty/diagnosis ; Middle Aged ; Female ; *Eye Diseases/diagnosis/epidemiology ; Macular Degeneration/epidemiology ; Risk Assessment/methods ; Adult ; Nutrition Surveys ; Cataract ; Risk Factors ; Aged, 80 and over ; Glaucoma ; Disease Progression ; },
abstract = {PURPOSE: To define frailty thresholds for accelerated progression of age-related ophthalmic diseases and inform precision intervention.

METHODS: Using NHANES 2005-2008 (n = 7081 adults ≥ 40 years), we constructed a 49-item frailty index (FI) via the deficit accumulation model. Missing data were addressed with complete-case analysis (n = 4120) and multiple imputation. Two analytic cohorts were defined: (1) objective diagnosis group and (2) composite diagnosis group. Multivariable logistic regression with restricted cubic splines (RCS) assessed associations between the FI and age-related macular degeneration (AMD), cataract, glaucoma, and diabetic retinopathy (DR). Bidirectional Mendelian randomization (MR) tested causality.

RESULTS: Findings were consistent across complete-case and imputed datasets. In continuous analyses, the FI was associated with AMD (composite odds ratio [OR] = 1.17; objective OR = 1.16), cataract (OR = 1.30), DR (OR = 1.33), and glaucoma (OR = 1.12). In categorical analyses, extreme frailty (FI > 0.45) conferred the highest risks: cataract (OR = 2.51), DR (OR = 2.04), AMD (OR = 1.77), and glaucoma (OR = 1.45). RCS analyses identified nonlinear thresholds at FI = 0.20 (AMD) and FI = 0.19 (cataract), whereas DR and glaucoma showed linear trends. MR supported a causal effect of frailty on four diseases, with no evidence for reverse causation.

CONCLUSIONS: Frailty was shown to accelerate ophthalmic disease progression. Three clinical implications are proposed here: (1) prioritized screening for individuals with FI > 0.45, (2) recognizing FI thresholds around 0.19 to 0.20 as potential early warning signals for accelerated AMD and cataract, and (3) integrating geriatric and ophthalmic care.

TRANSLATIONAL RELEVANCE: This study provides actionable FI thresholds to identify high-risk aging populations and reinforces frailty as a modifiable upstream driver of ocular aging.},
}

Humans
*Mendelian Randomization Analysis/methods
Male
Aged
*Frailty/diagnosis
Middle Aged
Female
*Eye Diseases/diagnosis/epidemiology
Macular Degeneration/epidemiology
Risk Assessment/methods
Adult
Nutrition Surveys
Cataract
Risk Factors
Aged, 80 and over
Glaucoma
Disease Progression

@article {pmid41396449,
year = {2025},
author = {Karaca, I and Wei, Y and Nelson, R and Sassen, SH and Daynes, K and Clark, F and Brown, T and Messina, A and Pfau, M and Zhang, Y and Schmitz-Valckenberg, S and Fleckenstein, M},
title = {Association of Mesopic and Dark-Adapted Retinal Sensitivity With Type 1 Macular Neovascularization in Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {45},
doi = {10.1167/iovs.66.15.45},
pmid = {41396449},
issn = {1552-5783},
mesh = {Humans ; Female ; Male ; Aged ; *Dark Adaptation/physiology ; Visual Field Tests ; *Mesopic Vision/physiology ; Visual Fields/physiology ; Aged, 80 and over ; Visual Acuity/physiology ; Tomography, Optical Coherence ; *Retina/physiopathology ; *Macular Degeneration/physiopathology/complications ; },
abstract = {PURPOSE: To assess the impact of type 1 macular neovascularization (MNV) on mesopic and dark-adapted (DA) cyan retinal sensitivity using fundus-controlled perimetry (FCP [microperimetry]) in patients with age-related macular degeneration (AMD).

METHODS: This index study includes baseline data from AMD patients with type 1 MNV without complete retinal pigment epithelium and outer retinal atrophy (cRORA). Mesopic and DA-cyan sensitivity were measured using FCP with standardized and MNV-lesion-tailored test grids. We applied linear mixed-effects models to compare retinal sensitivity in regions with versus without co-localized type 1 MNV. Age-specific hill-of-vision data that served as reference were estimated using Bayesian quantile regressions.

RESULTS: Of the 55 eyes with baseline data, 27 eyes without cRORA (27 patients; mean age, 76.8 ± 6.7 years; 74.1% female) were included in this detailed analysis. In regions co-localizing with type 1 MNV, unadjusted mesopic sensitivity was significantly increased by a mean of 2.10 dB (95% confidence interval [CI], 1.58-2.63; P < 0.001), whereas unadjusted DA-cyan sensitivity was significantly reduced by 3.12 dB (95% CI, 2.38-3.86; P < 0.001) compared to regions without evidence of MNV. When adjusting for age-specific hill-of-vision reference data, mesopic sensitivity remained significantly higher by 0.78 dB (95% CI, 0.29-1.28; P = 0.002) and DA-cyan sensitivity remained significantly lower by 2.07 dB (95% CI, 1.33-2.80; P < 0.001) in regions co-localizing with type 1 MNV versus those without MNV.

CONCLUSIONS: In AMD, areas overlying type 1 MNV showed higher mesopic but reduced DA-cyan sensitivity, suggesting localized preservation yet subtype-specific vulnerability. These findings will be further examined through structural analyses and prospective validation in our ongoing study.},
}

Humans
Female
Male
Aged
*Dark Adaptation/physiology
Visual Field Tests
*Mesopic Vision/physiology
Visual Fields/physiology
Aged, 80 and over
Visual Acuity/physiology
Tomography, Optical Coherence
*Retina/physiopathology
*Macular Degeneration/physiopathology/complications

@article {pmid41396384,
year = {2025},
author = {Li, Z and Jin, S and Xu, W and Zhang, M and Liu, X},
title = {Advances in the treatment of blinding retinal diseases.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {21},
pmid = {41396384},
issn = {1573-2630},
support = {No. 82371043//National Natural Science Foundation of China/ ; No.20240601014RC//the Project of Outstanding Talents in Scientific and Technological Innovation and Entrepreneurship for Middle-aged and Young Scientists of Jilin Provincial Science and Technology Department/ ; },
mesh = {Humans ; *Genetic Therapy/methods ; *Retinal Diseases/therapy/complications ; *Blindness/etiology/therapy ; *Retinal Pigment Epithelium/transplantation ; *Stem Cell Transplantation/methods ; },
abstract = {Blinding retinal diseases, including inherited and degenerative conditions, rank globally among the primary causes of permanent vision loss. While certain degenerative retinal diseases like age-related macular degeneration and diabetic retinopathy can be partially managed through intravitreal anti-VEGF injections or the use of complement inhibitors, most patients still lack effective treatment options. Recently, several promising therapeutic avenues have surfaced, such as stem cell-derived retinal pigment epithelium cell transplantation, gene therapy, and the implantation of retinal prostheses. This review summarizes recent clinical trials and advances in gene therapy for inherited retinal diseases, outlines techniques for retinal pigment epithelium cell transplantation, and discusses methods to improve graft survival. It also examines strategies for enhancing the resolution of retinal prostheses and explores their future clinical potential, providing new perspectives on the management of degenerative retinal conditions.},
}

Humans
*Genetic Therapy/methods
*Retinal Diseases/therapy/complications
*Blindness/etiology/therapy
*Retinal Pigment Epithelium/transplantation
*Stem Cell Transplantation/methods

@article {pmid41395976,
year = {2025},
author = {Shekho, N and Vergmann, AS and Pedersen, FN and Stokholm, L and Thinggaard, BS},
title = {Characterizing and assessing vision-related quality of life among patients discontinued treatment for neovascular age-related macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70044},
pmid = {41395976},
issn = {1755-3768},
support = {//The Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark/ ; 167-A6477//The Chief Physicians' Council Research Foundation (Overlægerådets Forskningsfond), Odense University Hospital/ ; },
abstract = {PURPOSE: This study characterized and assessed vision-related quality of life (VRQoL) in patients with neovascular age-related macular degeneration (nAMD) who discontinued treatment with intravitreal anti-vascular endothelial growth factor (anti-VEGF), comparing them to those undergoing treatment. Secondarily, it explored reasons for treatment discontinuation against medical advice.

METHODS: This survey-based cross-sectional study used data collected for the Danish study, "Identification of Patient-Reported Barriers in Treatment for nAMD" (I-OPTA) at Odense University Hospital, Denmark. I-OPTA included a self-developed questionnaire and the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Main outcomes were demographics, treatment details, NEI-VFQ-25 scores, and reasons for treatment discontinuation against medical advice. Linear regression models investigated the impact of variables on the composite NEI-VFQ-25 score.

RESULTS: The study included 172 (32.6%) patients who had discontinued treatment and 356 (67.4%) patients who were undergoing treatment; 10 (5.8%) discontinued against medical advice. Discontinued patients were older (median 81.0 years, p-value = 0.004), had lower best-corrected visual acuity (BCVA) in the worse-seeing eye (p-value<0.001), had a shorter treatment duration (p-value = 0.001) and lived alone (p-value = 0.044). Discontinued patients showed lower scores in all NEI-VFQ-25 domains except ocular pain. Higher BCVA correlated with a higher composite score of NEI-VFQ-25. Reasons for discontinuation against medical advice included treatment burden and perceived inefficacy.

CONCLUSION: Patients who discontinued treatment for nAMD report lower VRQoL, with lower BCVA in the worse-seeing eye, older age, living alone, and unilateral treatment possibly contributing to treatment discontinuation. Future studies on visual acuity and retinal fluid in this group could guide decisions on treatment discontinuation, emphasizing patients' quality of life.},
}

@article {pmid41394869,
year = {2025},
author = {Wei, Y and Lin, Y and Li, Y and Liu, J and Yang, Y and Chen, H and Han, Z and Wang, K and Qian, T and Ju, Y and Zheng, W},
title = {Redefining cell death: ferroptosis as a game-changer in ophthalmology.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1709354},
pmid = {41394869},
issn = {1664-3224},
mesh = {*Ferroptosis ; Humans ; Animals ; *Eye Diseases/metabolism/pathology/etiology ; Reactive Oxygen Species/metabolism ; *Ophthalmology ; Cell Death ; },
abstract = {Ferroptosis, recently proposed as a novel type of cell death, is characterized by unique characteristics and recognition functions. It is involved in diverse physiological processes and in the onset and progression of various diseases and is characterized by reactions between reactive oxygen species (ROS) and iron-dependent lipid peroxidation. This process is finely regulated by a variety of metabolic pathways. Ferroptosis fundamentally differs from conventional cell death mechanisms such as apoptosis, necrosis, and autophagy. In recent years, research on ferroptosis in the field of ophthalmology has gradually emerged, and a large amount of evidence has shown that it is closely related to the occurrence and development of ophthalmic diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), retinal ischemia-reperfusion injury (RIRI), retinitis pigmentosa, dry eye disease, cataracts, and glaucoma. This paper provides a comprehensive review of the latest advancements in ferroptosis within ophthalmological research and systematically describes the molecular mechanisms and pathophysiological significance of ferroptosis in the pathogenesis and progression of ophthalmic diseases. Exploring the mechanisms of ferroptosis holds promise for the delivery of novel molecular targets and therapeutic approaches to prevent and treat ophthalmic diseases. Additionally, its clinical translational and application are anticipated to surmount current therapeutic limitations and emerge as a significant direction for breakthroughs in the precision medicine era.},
}

*Ferroptosis
Humans
Animals
*Eye Diseases/metabolism/pathology/etiology
Reactive Oxygen Species/metabolism
*Ophthalmology
Cell Death

@article {pmid41394857,
year = {2025},
author = {Fan, Q and Li, Z},
title = {Breach and restoration of retinal immune privilege: barrier failure, innate dysregulation, and adaptive autoimmunity.},
journal = {Frontiers in immunology},
volume = {16},
number = {},
pages = {1703382},
pmid = {41394857},
issn = {1664-3224},
mesh = {Humans ; *Blood-Retinal Barrier/immunology ; *Autoimmunity ; *Immunity, Innate ; Animals ; *Immune Privilege/immunology ; *Adaptive Immunity ; *Retina/immunology/pathology ; *Retinal Diseases/immunology ; Uveitis/immunology ; },
abstract = {The retina preserves vision by tightly regulating inflammation ("immune privilege") via blood-retinal barriers, neuroglial checkpoints, and tolerogenic cues. This actively maintained-and potentially restorable-state is breached in major retinal diseases through three recurrent archetypes. We synthesize 2015-2025 advances into a framework of barrier failure, innate dysregulation, and adaptive autoimmunity. Across age-related macular degeneration (AMD), diabetic retinopathy (DR), retinitis pigmentosa (RP), and non-infectious uveitis (NIU): AMD exhibits complement-microglia para-inflammation with later outer-barrier compromise; DR exemplifies inner-BRB failure with inflammatory amplification; RP begins with degeneration-triggered innate activation and progresses to combined innate-adaptive injury; NIU represents T-cell-driven breach of the blood-retinal barrier. Interventional human evidence supports immunity as a therapeutic target: complement inhibition slows geographic atrophy; anti-VEGF reduces leak; intravitreal corticosteroids suppress inflammatory edema; and anti-TNF/IL-6R improve refractory NIU. Emerging strategies aim at privilege restoration-reinforcing myeloid checkpoints, tempering inflammasomes, and exploring tolerance-oriented approaches to re-educate adaptive immunity. Evidence from preclinical and early translational studies indicates that ocular tissues can imprint regulatory/anergic programs on pathogenic T cells, supporting mechanism-aligned, patient-tailored immunotherapy as a testable route to restore regulation, mitigate inflammation, and slow degeneration.},
}

Humans
*Blood-Retinal Barrier/immunology
*Autoimmunity
*Immunity, Innate
Animals
*Immune Privilege/immunology
*Adaptive Immunity
*Retina/immunology/pathology
*Retinal Diseases/immunology
Uveitis/immunology

@article {pmid41394258,
year = {2025},
author = {Blehm, C and Hall, B},
title = {Comparison of Visual Field Assessments Between the Humphrey Field Analyzer, Tempo, and Virtual Eye Elite Perimeters.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {19},
number = {},
pages = {4535-4542},
pmid = {41394258},
issn = {1177-5467},
abstract = {PURPOSE: To compare test duration and the agreement of summary metrics between the TEMPO, Virtual Eye ELITE (VEE), and Humphrey Field Analyzer (HFA) perimeters.

METHODS: This was a prospective, randomized, comparative study. Subjects were excluded if they were unable to tolerate ophthalmic imaging or had any ocular or systemic conditions that could affect visual field test results, such as age-related macular degeneration, peripheral retinal disease, or severe glaucoma. Eligible subjects were assessed at 1 visit with all perimeters for total bilateral acquisition time, mean deviation (MD), pattern standard deviation (PSD), foveal threshold (FT), visual field index (VFI), false positives and false negatives, and administered a questionnaire.

RESULTS: A total of 54 subjects completed the study. Mean bilateral visual field acquisition time differences were significant between TEMPO and HFA (p < 0.001) and TEMPO and VEE (p < 0.001), and not significant between HFA and VEE (p = 0.34). Mean MD differences were not significant between TEMPO and HFA (p = 0.96) and were significant for TEMPO and VEE (p = 0.01) and HFA and VEE (p = 0.02). Mean PSD differences were not significant between TEMPO and HFA (p = 0.27), TEMPO and VEE (p = 0.72), or HFA and VEE (p = 0.72). Mean foveal threshold differences were significant between TEMPO and HFA (p < 0.001), TEMPO and VEE (p < 0.001), and HFA and VEE (p < 0.001). A significantly higher percentage of subjects reported agreement that the testing was "Easy" to perform with the TEMPO compared to HFA (p < 0.001), TEMPO compared to VEE (p = 0.006), and with VEE compared to HFA (p = 0.002).

CONCLUSION: The results suggest similar summary metrics between the HFA, TEMPO, and VEE perimeters. There was faster acquisition time with the TEMPO. These results also indicate the potential for streamlined clinical workflow.},
}

@article {pmid41393127,
year = {2025},
author = {Lin, TH and Lin, YY and Huang, YT and Huang, YC and Tien, PT and Wan, L and Lin, HJ},
title = {Chronic kidney disease increases the risks of age-related macular degeneration: a systematic review and meta-analysis.},
journal = {Frontiers in medicine},
volume = {12},
number = {},
pages = {1635766},
pmid = {41393127},
issn = {2296-858X},
abstract = {IMPORTANCE: Age-related macular degeneration (AMD) and chronic kidney disease (CKD) are common causes of morbidity, with systemic risk factors shared. Clarifying the association between the two is crucial to guiding comprehensive management.

OBJECTIVE: This study aimed to systematically review current and latest evidence on the influence of CKD on AMD prevalence. An investigation was performed into various AMD stages and how different CKD severities exert their effects.

DATA SOURCES: Databases of PubMed and Embase were searched from their inception to 11 November 2024. Reference lists of studies were reviewed, and relevant researchers were contacted. The study was accepted and registered with PROSPERO (CRD420250612669).

STUDY SELECTION: Eligible studies of the current review are observational, peer-reviewed, and include quantitative comparisons of AMD prevalence between populations with and without CKD. Studies with overlapping data or investigating AMD incidence were excluded. Twenty studies met the inclusion criteria from the 3,218 initially identified.

DATA EXTRACTION AND SYNTHESIS: We extracted data and assessed study quality using the Appraisal tool for Cross-Sectional Studies (AXIS) tool for cross-sectional studies. Our meta-analyses followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and were conducted with Review Manager 5.4.1. Risk of bias was evaluated using the AXIS quality appraisal tool, and the overall certainty of evidence was qualitatively assessed following the GRADE approach.

MAIN OUTCOMES AND MEASURES: Primary outcomes are the prevalence of all-stage, early-stage, and late-stage AMD among CKD and non-CKD patients. Secondary outcomes investigated AMD prevalence among patients with different CKD stages. We reported in our analyses the risk ratios (RRs) with 95% confidence intervals (CIs).

RESULTS: All-stage AMD prevalence was found to be higher among CKD patients (RR: 1.65; 95% CI: 1.49-1.83). Similarly, early-stage AMD was more prevalent among CKD patients (RR: 1.47; 95% CI: 1.26-1.71). In late-stage AMD, an even stronger association was shown (RR: 3.72; 95% CI: 2.14-6.45). Meanwhile, there was no significant difference in AMD prevalence between moderate and advanced CKD stages (RR: 1.08; 95% CI: 0.48-2.46).

CONCLUSION AND RELEVANCE: Our findings indicate that CKD is significantly associated with higher AMD prevalence. These findings suggest the effects of shared systemic mechanisms and underscore the need for ophthalmic screening in CKD patients. Further studies are needed to strengthen causality and expand generalizability beyond the Asian population.

The systematic review was registered in PROSPERO (CRD420250612669).},
}

@article {pmid41393074,
year = {2025},
author = {Nagaoka, K and Makino, S and Inoda, S and Kaburaki, T},
title = {Secondary Angle Closure Glaucoma due to Massive Subretinal and Suprachoroidal Hemorrhage in Neovascular Age-Related Macular Degeneration: Clinical Case and Literature Review.},
journal = {Case reports in ophthalmological medicine},
volume = {2025},
number = {},
pages = {2230622},
pmid = {41393074},
issn = {2090-6722},
abstract = {Massive subretinal hemorrhage secondary to neovascular age-related macular degeneration (nAMD) is relatively uncommon, and reports of secondary angle closure glaucoma associated with such hemorrhage are even rarer. We report a case of a 93-year-old woman with a history of nAMD who developed this condition, along with a review of the relevant literature.},
}

@article {pmid41392555,
year = {2025},
author = {Andreev, V and Yakovleva, M and Kostyukov, A and Sokolova, V and Shcheslavskiy, V and Goltsman, G and Feldman, T and Kuzmin, V and Ostrovsky, M and Morozov, P},
title = {Interrogation of Retinal Lipofuscin by Fluorescence Lifetime Imaging Microscopy.},
journal = {Journal of biophotonics},
volume = {},
number = {},
pages = {e202500418},
doi = {10.1002/jbio.202500418},
pmid = {41392555},
issn = {1864-0648},
support = {23-65-10005//Russian Science Foundation/ ; 122041400102-9//Ministry of Science and Higher Education of the Russian Federation/ ; 23-SCH06-20//Moscow State University Program of Development/ ; },
abstract = {Age-related macular degeneration is a disease that affects the middle part of the vision and involves pathological alterations in the retinal pigment epithelium. Accurate and timely evaluation of the retinal pigment epithelium is a cornerstone of effective treatment planning. In this study, we present the development of a preclinical method for early diagnostics of age-related macular degeneration using time and spectral characteristics of fluorescence of lipofuscin granules from the retinal pigment epithelium. Using the unique system based on a superconducting single-photon detector and time-correlated single-photon counting electronics integrated in the confocal laser scanning microscope we determined the parameters of fluorescence (distribution long and short fluorescence lifetime components and their contribution to the total fluorescence signal as well as fluorescence spectral shift) that have a diagnostic value for differentiation of the normal and pathological states in the degenerative diseases of the retina and retinal pigment epithelium.},
}

@article {pmid41390091,
year = {2025},
author = {Tao, L and He, D and Chen, Y and Cai, P and Yang, K and Wu, J and Liao, C and Chen, J and Wu, Y},
title = {Gene editing of JNK alleviates sodium iodate-induced retinal degeneration in mice.},
journal = {Life sciences},
volume = {},
number = {},
pages = {124145},
doi = {10.1016/j.lfs.2025.124145},
pmid = {41390091},
issn = {1879-0631},
abstract = {PURPOSE: Dry age-related macular degeneration (dry AMD) still lacks effective treatment strategies due to its complex mechanisms. Although c-Jun N-terminal kinase (JNK) signaling has been reported to be associated with retinal degeneration in dry AMD, the efficacy of JNK gene editing in treating dry AMD remains unclear. This study aims to investigate the protective potential of JNK genetic inhibition in a sodium iodate (SI)-induced retinal degeneration model that recapitulates the key features of human dry AMD.

METHODS: A retinal degeneration model was constructed from a single intraperitoneal injection of 50 mg/kg body weight SI into C57BL/6 J mice. The retina was examined by electroretinography (ERG), fundus imaging, optical coherence tomography (OCT), hematoxylin and eosin (H&E) staining, and whole-mount ZO-1 immunofluorescence staining. Protein levels were determined using Western blotting. Jnk1[+/-]Jnk2[-/-] mice were obtained by crossbreeding Jnk2[-/-] mice with Jnk1[+/-] mice.

RESULTS: In C57BL/6 J mice, SI robustly activated JNK signaling in the retinal pigment epithelium (RPE)/choroid, triggering a parallel loss of retinal function and structural integrity. By contrast, Jnk1[+/-]Jnk2[-/-] mice were largely protected: both the SI-evoked JNK response in the RPE/choroid and the ensuing retinal degeneration were markedly attenuated.

CONCLUSIONS: Gene editing of JNK is effective in ameliorating SI-driven retinal injury and may serve as a promising therapeutic avenue for dry AMD.},
}

@article {pmid41389973,
year = {2025},
author = {Xiong, X and Li, Q and Zhang, Y and Liu, P and Pan, Y and Song, Q},
title = {Exploring copper metabolism and cuproptosis, and their implications in ocular diseases.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178472},
doi = {10.1016/j.ejphar.2025.178472},
pmid = {41389973},
issn = {1879-0712},
abstract = {Copper is a vital trace element for all living organisms and plays an important role in numerous physiological functions, including the formation of mitochondrial respiratory chain complexes, antioxidant defense, and signal transduction. However, excess copper can cause cellular toxicity and initiate a form of cell death that is characterized by the aggregation of lipoylated proteins and a reduction in Fe-S cluster proteins. This series of events can culminate in mitochondrial process of respiratory dysfunction known as cuproptosis. Excessive copper can also inhibit the ubiquitin-proteasome system, which results in the accumulation of harmful proteins and a vicious cycle of Fenton and Haber-Weiss reactions that trigger oxidative stress and cellular damage. The eye, particularly the retina, is one of the most energy-dependent tissues in the body and has an extraordinary dependence on mitochondrial function. Dysregulated copper-ion levels can lead to mitochondrial dysfunction, which can cause various ocular diseases, including uveal melanoma, age-related macular degeneration, and diabetic retinopathy. Therefore, the relationship between copper and ocular diseases provides promising research opportunities. This review summarizes recent research findings on copper metabolism, cuproptosis, and their implications in ocular diseases. It also introduces potential therapeutic approaches for related diseases, including copper chelation therapy, copper ionophores and nanomedicine, and genetic treatment strategies.},
}

@article {pmid41390463,
year = {2025},
author = {Dastgheib, KA},
title = {Histopathologic evidence of VEGF in early neovascular AMD: from a 1992 hypothesis to a 1994 discovery - a historical perspective.},
journal = {International journal of retina and vitreous},
volume = {11},
number = {1},
pages = {137},
pmid = {41390463},
issn = {2056-9920},
abstract = {BACKGROUND: In the early1990s, neovascular age-related macular degeneration (nAMD) was the leading cause of irreversible vision loss in older adults, yet its molecular basis remained unknown. In 1992, a hypothesis was proposed in which localized hypoxia could trigger vascular endothelial growth factor (VEGF)-mediated choroidal neovascularization in nAMD. Although hypoxia was recognized in ischemic retinopathies, nAMD was not considered a hypoxia-mediated retinal vascular disease.

MAIN BODY: In 1994, this hypothesis was tested using antigen retrieval immunohistochemistry on paraffin-embedded whole human eye sections with early nAMD. The study demonstrated strong VEGF immunoreactivity in the retinal pigment epithelium in the macular area but not in normal control eyes, providing the first direct histopathologic evidence of VEGF expression at the site of disease in intact human eyes with early nAMD. Until that point, the role of VEGF in ischemic retinopathies was being uncovered, but its involvement in early-stage nAMD had not yet been demonstrated.

CONCLUSION: The 1992-1994 work established both the hypothesis and the first direct tissue evidence linking VEGF to early nAMD. This discovery, made just over a decade before the advent of anti-VEGF therapy, anticipated one of ophthalmology's most transformative achievements, preserving vision for millions worldwide.},
}

@article {pmid41390041,
year = {2025},
author = {Lin, Z and Deng, H and Wang, S and Wang, Z and Yang, G and Huang, K},
title = {Apoferritin-conjugated melanin nanoparticles rescue photoreceptor degeneration via dual iron chelation and ROS scavenging in dry AMD therapy.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {149586},
doi = {10.1016/j.ijbiomac.2025.149586},
pmid = {41390041},
issn = {1879-0003},
abstract = {Oxidative stress in the retina and dysregulation of iron homeostasis are established as central pathogenic mechanisms in dry age-related macular degeneration (dAMD). Nonetheless, effective clinical treatments to counteract retinal degeneration in this condition are still absent. Our research began with developing a single-cell transcriptome profile of retinal tissue subjected to sodium iodate (NaIO3)-induced oxidative injury. This analysis identified ferroptosis in photoreceptor cells as a key driver of disease advancement. Apoferritin (AFn) is a hollow, spherical protein nanocage formed by 24 self-assembled subunits, enabling supramolecular iron storage through ferroxidase-mediated mineralization while providing dynamic iron buffering and antioxidant protection in biological systems. We then engineered a biomimetic nanoparticle, AFn-MNP, by combining Afn with melanin nanoparticles (MNP). AFn-MNP displayed significant ferrous ion-chelating ability and antioxidant activity, effectively mitigating NaIO3-triggered photoreceptor ferroptosis in vitro and in vivo. Significantly, a single intravitreal injection of 10 μg AFn-MNP effectively counteracted visual impairment in NaIO3-induced dAMD model mice, reversed damage to photoreceptor synaptic terminals, and significantly alleviated photoreceptor degeneration and retinal oxidative injury.In summary, our results indicate that AFn-MNP holds significant promise as a novel therapy for dAMD and other retinal degenerative diseases linked to oxidative damage and impaired iron metabolism.},
}

@article {pmid41388211,
year = {2025},
author = {Srivastava, V and Yadav, P and Yadav, A and Parashar, P},
title = {Artificial Intelligence in Ocular Drug Delivery: Precision Drug Delivery's New Horizon.},
journal = {AAPS PharmSciTech},
volume = {27},
number = {1},
pages = {55},
pmid = {41388211},
issn = {1530-9932},
mesh = {Humans ; *Artificial Intelligence/trends ; *Drug Delivery Systems/methods ; *Eye Diseases/drug therapy ; Precision Medicine/methods ; Administration, Ophthalmic ; Animals ; Machine Learning ; Eye/drug effects/metabolism ; },
abstract = {BACKGROUND: Artificial intelligence is emerging as a transformative force in pharmaceutical sciences by enabling data-driven decision-making, automation, and predictive modeling. In ocular drug delivery, where therapeutic efficacy is hindered by complex anatomical and physiological barriers, AI presents significant opportunities to overcome these challenges. Its ability to optimize drug combinations, design smart delivery systems, and personalize therapies underscores its relevance in advancing ophthalmic care.

AREA COVERED: This review explores the intersection of AI and ophthalmic therapeutics, highlighting its role in formulation design, disease prediction, patient-specific treatment strategies, and smart delivery platforms, and outlines future research directions to bridge current gaps. Machine learning is advancing ocular drug delivery by optimizing nano-formulations, predicting release kinetics, and modeling pharmacokinetics. Alongside AI-powered diagnostics and integration with biosensors, contact lenses, and implants, these innovations are driving real-time monitoring and truly personalized ocular therapy and early detection and monitoring ocular diseases such as glaucoma, diabetic retinopathy, and macular degeneration. Challenges including limited clinical validation, model interpretability, data security, and regulatory complexities are highlighted. Furthermore, current gaps such as the lack of comprehensive studies on AI-assisted stimuli-responsive carriers and integration with patient-specific data are identified. Future directions emphasize explainable AI, smart biomaterials, and robust ethical-regulatory frameworks for clinical translation.

EXPERT OPINION: AI integration in ocular therapeutics marks a paradigm shift toward precision drug delivery and personalized care. Despite progress, challenges in explainability, regulation, and validation remain, yet innovations in AI-driven nanocarriers, smart systems, and real-time monitoring hold the potential to revolutionize ocular pharmacology overcoming limitations of conventional therapies.},
}

Humans
*Artificial Intelligence/trends
*Drug Delivery Systems/methods
*Eye Diseases/drug therapy
Precision Medicine/methods
Administration, Ophthalmic
Animals
Machine Learning
Eye/drug effects/metabolism

@article {pmid41388185,
year = {2025},
author = {Rinaldi, M and Cennamo, G and Concilio, M and Corvino, G and Riccardo, A and Nubi, R and Costagliola, C},
title = {Aflibercept 8 mg in Neovascular AMD-A Fast-Drying Anti-VEGF Drug: A Prospective Morpho-Functional Pilot Study.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {41388185},
issn = {2193-8245},
abstract = {INTRODUCTION: This study investigated early anatomical and functional outcomes in patients with treatment-naïve neovascular age-related macular degeneration (nAMD) treated with 8 mg aflibercept compared to patients treated with the standard dose of 2 mg aflibercept using spectral domain optical coherence tomography (SD-OCT), microperimetry, and macular pigment optical density (MPOD) after loading phase administration.

METHODS: This prospective, observational study included 30 eyes of 30 patients (mean age 70 ± 5 years; 15 male, 15 female) recruited between January and June 2025 at the Eye Clinic of the University of Naples "Federico II". Patients were assigned to one of two age- and gender-matched groups receiving intravitreal injections of aflibercept at the dose of 2 mg (group A) or 8 mg (group B). All patients underwent complete ophthalmological examination, SD-OCT, OCT angiography, microperimetry, fixation stability, and measurement of MPOD at baseline, month 2, and month 4.

RESULTS: Group B showed an improvement in all parameters, compared to group A, in particular: a greater reduction in central macular thickness (CMT) (p = 0.008), an improvement in best-corrected visual acuity (BCVA) (p = 0.012), increased retinal sensitivity (p = 0.015), increased MPOD (p = 0.027), and reduced bivariate contour ellipse area (BCEA) (p = 0.039). Group B showed a faster drying rate during the first 2 months (70 vs. 40 μm/month) and overall at month 4.

CONCLUSIONS: Intravitreal injections of aflibercept 8 mg resulted in significant short-term anatomical and functional improvement compared to standard dose and thus appear to be an effective option to achieve faster results in nAMD. MPOD can be considered as a potential new biomarker of macular health to study retinal functional response.

TRIAL REGISTRATION: The research protocol was registered on ClinicalTrials.gov (NCT07074054).},
}

@article {pmid41385282,
year = {2025},
author = {Sagiv, RG and Rosenblatt, HN and Zamir, E and Altarescu, A and Ben-Zaken, SG and Rotfogel, Z},
title = {Efficiency of anti-vascular endothelial growth factor drug switch in patients who did not respond to a series of bevacizumab injections.},
journal = {Indian journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.4103/IJO.IJO_1740_25},
pmid = {41385282},
issn = {1998-3689},
abstract = {PURPOSE: To assess the effectiveness of switching anti-vascular endothelial growth factor (VEGF) agents in eyes with retinal pathologies that poorly respond to intravitreal bevacizumab injections.

METHODS: We compared central macular thickness (CMT) and VA between eyes with suboptimal responses to at least three bevacizumab injections that either continued with bevacizumab or switched to aflibercept or ranibizumab. Eyes were categorized into group D (DME), group N (neovascular age-related macular degeneration [nAMD]), and group A - all eyes (D and N plus eyes with retinal vein occlusion (RVO) or pseudophakic central macular edema [PCME]). Each group was further divided into those continuing bevacizumab (D1, N1, A1) or switching to aflibercept or ranibizumab (D2, N2, A2).

RESULTS: A total of 21 eyes were included in group D (8 in D1 and 13 in D2), 28 in group N (14 in N1 and 14 in N2), and 59 eyes in group A (25 in A1 and 34 in A2). In all eyes with treatment shift, CMT decreased: 38.5 (SD: 46.2), 92.6 (SD: 106.8), and 82.1 (SD: 115.6) microns in D2, N2, and A2, respectively. CMT difference was statistically significant between N1 versus N2 and between A1 versus A2 (P = 0.025 and 0.004, respectively). No significant difference in VA was observed.

CONCLUSION: Switching anti-VEGF agents appears anatomically beneficial in nonresponding eyes. Notably, the inclusion of a control group continuing bevacizumab despite poor response allows for a more reliable evaluation of treatment efficacy, addressing a key limitation of prior studies and contributing to the evidence-based rationale for agent switching.},
}

@article {pmid41385093,
year = {2025},
author = {Lingardo, S and Sacconi, R and Balduzzi, E and Beretta, F and Menean, M and Querques, G},
title = {The spectrum of pachychoroid neovasculopathy.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41385093},
issn = {1435-702X},
abstract = {PURPOSE: To provide a comprehensive overview of pachychoroid neovasculopathy (PNV), focusing on its current understanding in terms of clinical behavior, multimodal retinal imaging characteristics, and treatment.

METHODS: A narrative review of the literature on PNV was conducted using the following keywords: pachychoroid neovasculopathy, pachychoroid, pachychoroid disease spectrum, pachychoroid pigment epitheliopathy, central serous chorioretinopathy, polypoidal choroidal vasculopathy.

RESULTS: PNV is a clinical entity within the pachychoroid disease spectrum, typically presenting as type 1 choroidal neovascularization (CNV). It may arise either directly from pachychoroid pigment epitheliopathy (PPE) without prior central serous chorioretinopathy (CSC) or from chronic CSC. PNV is frequently misdiagnosed as neovascular age-related macular degeneration (nAMD), particularly in patients older than 50 years, making multimodal retinal imaging essential for distinguishing its characteristic features from CNV secondary to AMD. The therapeutic management of PNV depends on its underlying initial condition and differs from the treatment strategy for CNV secondary to AMD.

CONCLUSIONS: Recognizing PNV as a distinct entity is crucial for optimizing diagnosis and treatment. Multimodal retinal imaging is essential to ensure appropriate therapeutic management.

KEY MESSAGES: What is known? Pachychoroid neovasculopathy (PNV) is a distinct clinical entity within the pachychoroid disease spectrum, frequently misdiagnosed as neovascular age-related macular degeneration (nAMD). What is new? PNV includes subtypes arising from pachychoroid pigment epitheliopathy or chronic central serous chorioretinopathy, which differ in treatment responses and strategies. Multimodal retinal imaging plays an essential role in differentiating PNV from nAMD. The lack of standardized diagnostic criteria for PNV highlights the need for shared definitions to improve PNV classification, patient stratification, and treatment selection.},
}

@article {pmid41384795,
year = {2025},
author = {Jonas, JB and Panda-Jonas, S and Xu, J and Jonas, RA and Wang, YX},
title = {Changes of the Optic Nerve Head and Macula in High Myopia in a 10-Year Follow-Up: The Beijing Eye Study.},
journal = {Investigative ophthalmology & visual science},
volume = {66},
number = {15},
pages = {39},
doi = {10.1167/iovs.66.15.39},
pmid = {41384795},
issn = {1552-5783},
mesh = {Humans ; *Optic Disk/pathology ; Male ; Female ; Follow-Up Studies ; Aged ; Tomography, Optical Coherence/methods ; *Macula Lutea/pathology ; Middle Aged ; *Myopia, Degenerative/epidemiology/diagnosis ; Beijing/epidemiology ; Incidence ; Disease Progression ; China/epidemiology ; *Myopia ; },
abstract = {PURPOSE: To assess the incidence of myopic changes of the optic nerve head and macula in highly myopic eyes.

METHODS: All highly myopic eyes (axial length >26.0 mm or refractive error ≤-6.0 diopters) examined in the longitudinal population-based Beijing Eye Study 2001/2011 underwent fundus photography (2001/2011) and optic coherence tomography (2011).

RESULTS: The study included 89 highly myopic eyes (patient age, 65.0 ± 9.8 years). Progressive macula changes were detected in 63 of 89 eyes (71%), including increases in fundus tessellation (n = 61 [69%]), diffuse chorioretinal atrophy (n = 15 [17%]), lacquer cracks (n = 12 [14%]), patchy atrophies (n = 8 [9%]), macular atrophy (n = 6 [7%]), and overall myopic macular degeneration stage (n = 23 [26%]). Without considering fundus tessellation changes, any macular change was detected in 31 of 80 eyes (35%). Progressive optic nerve head changes were found in 69 of 89 eyes (78%), including optic disc diminution (n = 28 [32%]), disc enlargement (n = 13 [15%]), change in disc shape (n = 36 [40%]), enlargement in beta/gamma zone (n = 68 [76%]) or delta zone (n = 22 [25%]), and lengthening of parapapillary retinal vessels (n = 47 [53%]). Any type of progression of the macula and/or optic nerve head was detected in 74 of 89 eyes (83%), and without considering fundus tessellation changes in 70 of 89 eyes (79%). Higher incidence of any macular change (fundus tessellation change not considered) and of optic nerve head changes correlated with longer axial length (odds ratio [OR], 2.15 [P < 0.001] and OR, 2.20 [P = 0.02], respectively) and older age (OR, 1.11 [P = 0.001] and OR, 1.08 [P = 0.02], respectively). Optic disc diminution correlated with disc shape change from a more circular to an elliptical shape (OR, 37.9; 95% confidence interval, 9.7-148.0; P < 0.001) and in all eyes with beta/gamma zone enlargement.

CONCLUSIONS: Over the 10-year follow-up, >75% of highly myopic eyes showed progressive myopic changes of the optic nerve head and macula.},
}

Humans
*Optic Disk/pathology
Male
Female
Follow-Up Studies
Aged
Tomography, Optical Coherence/methods
*Macula Lutea/pathology
Middle Aged
*Myopia, Degenerative/epidemiology/diagnosis
Beijing/epidemiology
Incidence
Disease Progression
China/epidemiology
*Myopia

@article {pmid41383834,
year = {2025},
author = {Li, MM and Zhang, H and Cen, ZM and Su, DW},
title = {Management of submacular hemorrhage secondary to age-related macular degeneration with vitrectomy and subretinal tissue plasminogen activator injection: Outcomes and prognostic factors.},
journal = {SAGE open medicine},
volume = {13},
number = {},
pages = {20503121251403361},
pmid = {41383834},
issn = {2050-3121},
abstract = {PURPOSE: To evaluate the efficacy of pars plana vitrectomy combined with subretinal tissue plasminogen activator injection, pneumatic displacement, and intraoperative intravitreal antivascular endothelial growth factor therapy for treating submacular hemorrhage secondary to polypoidal choroidal vasculopathy or neovascular age-related macular degeneration.

METHODS: This retrospective study enrolled 28 patients who were diagnosed with submacular hemorrhage secondary to polypoidal choroidal vasculopathy or neovascular age-related macular degeneration, all of whom received a minimum follow-up period of 6 months. Key preoperative parameters, such as submacular hemorrhage height and diameter, tissue plasminogen activator dosage, and hemorrhage duration, were documented. Postoperative outcomes evaluated included the degree of submacular hemorrhage displacement, visual acuity changes, incidence of complications, and the requirement for additional intravitreal antivascular endothelial growth factor injections during the follow-up period.

RESULTS: The mean patient age was 66.71 ± 10.62 years. The mean visual acuity progressively improved from a preoperative logMAR of 1.57 ± 0.64 to 1.26 ± 0.67, 1.15 ± 0.59, 1.14 ± 0.55, and 1.12 ± 0.56 at postoperative months 1, 3, and 6, respectively. Complete hemorrhage displacement was achieved in 85.71% (24/28) of cases. Preoperative hemorrhage duration was significantly negatively correlated with postoperative best-corrected visual acuity at 1 month (r = 0.46; p = 0.013), 3 months (r = 0.42; p = 0.028), 6 months (r = 0.41; p = 0.032), and final follow-up (r = 0.38; p = 0.047).

CONCLUSIONS: Pars plana vitrectomy with tissue plasminogen activator subretinal injection, pneumatic displacement, and intraoperative vitreous antivascular endothelial growth factor injection represents a safe and effective approach for managing submacular hemorrhage secondary to polypoidal choroidal vasculopathy and neovascular age-related macular degeneration. The duration of submacular hemorrhage emerges as the most critical prognostic factor for final visual outcomes. Patients with hemorrhage duration exceeding 14 days demonstrate a significantly reduced likelihood of achieving favorable visual outcomes.},
}

@article {pmid41383281,
year = {2025},
author = {Cheng, S and Ma, Y and Huang, F and Luo, R and Han, L and He, L and Yuan, ZX},
title = {Mesenchymal Stem Cell-Derived Exosomes for Ocular Diseases: Therapeutic Mechanisms and Clinical Perspectives.},
journal = {International journal of nanomedicine},
volume = {20},
number = {},
pages = {14521-14550},
pmid = {41383281},
issn = {1178-2013},
mesh = {*Exosomes/chemistry/transplantation ; Humans ; *Mesenchymal Stem Cells/cytology/metabolism ; *Eye Diseases/therapy ; Animals ; Drug Delivery Systems/methods ; },
abstract = {Ocular diseases represent a major and increasing public health concern. Although current treatment options are available, the management of complex cases, such as corneal diseases, diabetic retinopathy, glaucoma, age-related macular degeneration, and uveitis, remains inadequate. Recent studies have demonstrated that mesenchymal stem cell-derived exosomes (MSC-Exos), obtained from bone marrow, adipose tissue, and umbilical cord, have emerged as a promising cell-free therapeutic platform for various ocular diseases. These nanovesicles can be delivered via systems such as topical eye drops and intravitreal injection, targeting ocular tissues to exert anti-inflammatory, anti-apoptotic, and tissue-repairing effects. This review systematically synthesizes recent advances and the molecular mechanisms underlying the use of MSC-Exos in treating ocular diseases. Moreover, it provides an in-depth discussion of the challenges in the clinical application of MSC-Exos in ophthalmology, including standardized production, dosage optimization, delivery system improvement, and targeting enhancement, and proposes engineered targeting strategies based on surface modification and carrier optimization. Overall, this work establishes a rigorous framework for advancing MSC-Exos from experimental models to clinical implementation, offering novel therapeutic strategies through these innovative biopharmaceuticals for previously untreatable ocular conditions.},
}

*Exosomes/chemistry/transplantation
Humans
*Mesenchymal Stem Cells/cytology/metabolism
*Eye Diseases/therapy
Animals
Drug Delivery Systems/methods

@article {pmid41381091,
year = {2025},
author = {Shi, Q and Zhan, D and Wang, W and Wu, X and Sheng, S and Wang, Y},
title = {Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study.},
journal = {The Journal of international medical research},
volume = {53},
number = {12},
pages = {3000605251404265},
doi = {10.1177/03000605251404265},
pmid = {41381091},
issn = {1473-2300},
mesh = {Humans ; *Mendelian Randomization Analysis ; Genome-Wide Association Study ; *Retinal Diseases/genetics/complications ; *Alzheimer Disease/genetics ; *Cognitive Dysfunction/genetics ; Polymorphism, Single Nucleotide ; Genetic Predisposition to Disease ; Macular Degeneration/genetics ; Dementia, Vascular/genetics ; *Lewy Body Disease/genetics ; },
abstract = {ObjectiveThis study employed a bidirectional two-sample Mendelian randomization approach to investigate the causal links between Alzheimer's disease, Lewy body dementia, vascular dementia, and various retinal diseases.MethodsSummary data from large-scale genome-wide association studies of European ancestry were used to select genetic variants as instrumental variables. Causal estimates were derived using the inverse variance-weighted method, complemented by Mendelian randomization-Egger, weighted median, and weighted mode analyses to ensure robustness.ResultsGenetically predicted Alzheimer's disease was associated with a reduced risk of disorders of the choroid and retina (odds ratio = 0.93, 95% confidence interval: 0.88-0.98), retinal detachments and breaks (odds ratio = 0.90, 95% confidence interval: 0.84-0.97), and retinal detachment with retinal break (odds ratio = 0.84, 95% confidence interval: 0.74-0.95). Lewy body dementia was negatively associated with age-related macular degeneration (odds ratio = 0.88, 95% confidence interval: 0.79-0.98), disorders of the choroid and retina (odds ratio = 0.96, 95% confidence interval: 0.93-0.99), and degeneration of the macula (odds ratio = 0.93, 95% confidence interval: 0.88-0.98). Vascular dementia showed negative associations with age-related macular degeneration (odds ratio = 0.93, 95% confidence interval: 0.87-0.99) and degeneration of the macula (odds ratio = 0.96, 95% confidence interval: 0.93-0.99). Conversely, reverse Mendelian randomization indicated that genetic liability to macular degeneration and choroidal/retinal disorders was causally associated with cognitive performance and a reduced risk of Alzheimer's disease.ConclusionsFindings support inverse causal relationships in which specific dementias may reduce retinal disease risk and vice versa, suggesting complex shared biological mechanisms.},
}

Humans
*Mendelian Randomization Analysis
Genome-Wide Association Study
*Retinal Diseases/genetics/complications
*Alzheimer Disease/genetics
*Cognitive Dysfunction/genetics
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Macular Degeneration/genetics
Dementia, Vascular/genetics
*Lewy Body Disease/genetics

@article {pmid41378371,
year = {2025},
author = {Meng, N and Xia, L and Gong, Y and Shi, C and Lu, P},
title = {A Bibliometric Analysis of Research Progress on Age-Related Macular Degeneration and Autophagy From 2010 to 2024.},
journal = {Journal of ophthalmology},
volume = {2025},
number = {},
pages = {6670966},
pmid = {41378371},
issn = {2090-004X},
abstract = {BACKGROUND: Autophagy regulates intracellular metabolism and is crucial in the development of age-related macular degeneration (AMD). Despite the growing number of studies on AMD and autophagy in recent years, bibliometric analyses in this field remain scarce. Therefore, a bibliometric analysis was applied to explore the research trends and hot spots of this field in this study.

METHODS: We collected publications on autophagy in AMD from the MEDLINE database, covering the period from January 2010 to October 2024. The "bibliometrix" R package (Version R 4.2.3) was utilized for bibliometric analysis, and WPS Excel, PowerPoint, and Word (12.1.0.18276) were used to manage data and create related tables.

RESULTS: A total of 349 articles were included. The amount of literature was on the rise from 2010 to 2024. China leads in article quantity, whereas the United States holds the most influence. Although Finland ranks the third position in publication volume, followed by China and the United States, Finland led research in this field, with the University of Eastern Finland being the most active and prolific institution and Kaarniranta Kai as the most productive and influential author. International Journal of Molecular Sciences and Autophagy is the journal with the most volume. The three most referenced studies primarily examine the interplay between inflammation, oxidative stress, and autophagy in retinal pigment epithelial cells. The analysis for keywords found that mitophagy has also received increasing attention in this field.

CONCLUSIONS: This bibliometric analysis identifies current research hotspots in autophagy related to AMD and informs future research directions. Future trends in this field may involve identifying and developing novel autophagy-targeted therapies for the prevention and treatment of AMD.},
}

@article {pmid41377141,
year = {2025},
author = {Zhang, LL and Yu, JM and Fan, ZX and Xie, WQ and Zou, L and Sheng, F},
title = {Regulated cell death in age-related macular degeneration: Regulatory mechanisms and therapeutic potential.},
journal = {Journal of pharmaceutical analysis},
volume = {15},
number = {11},
pages = {101285},
pmid = {41377141},
issn = {2214-0883},
abstract = {Age-related macular degeneration (AMD) represents a predominant cause of blindness among older adults, with limited therapeutic options currently available. Oxidative stress, inflammation, and retinal pigment epithelium injury are recognized as key contributors to the pathogenesis of AMD. Regulated cell death plays a pivotal role in mediating cellular responses to stress, maintaining tissue homeostasis, and contributing to disease progression. Recent research has elucidated several regulated cell death pathways-such as apoptosis, ferroptosis, pyroptosis, necroptosis, and autophagy-that may contribute to the progression of AMD owing to cell death in the retinal pigment epithelium. These discoveries open new avenues for therapeutic interventions in patients with AMD. In this review, we provide a comprehensive summary and analysis of the latest advancements regarding the relationship between regulated cell death and AMD. Moreover, we examined the therapeutic potential of targeting regulated cell death pathways for the treatment and prevention of AMD, highlighting their roles as promising targets for future therapeutic strategies.},
}

@article {pmid41377065,
year = {2026},
author = {Fragiotta, S and Querques, G and Polito, MS and Costanzo, E and Rossi, T and Varano, M and Pannarale, FM and Sakurada, Y and Parravano, M},
title = {Structural Biomarkers Influencing Drusenoid Pigment Epithelial Detachment Lifecycle and the Development of Late Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100977},
pmid = {41377065},
issn = {2666-9145},
abstract = {PURPOSE: Drusenoid pigment epithelial detachment (dPED) is a notable phenotype in age-related macular degeneration (AMD), often evolving into macular complications such as macular neovascularization (MNV) and geographic atrophy (GA). The aim of this study was to identify potential prognostic biomarkers associated with the development of both MNV and GA.

DESIGN: A retrospective cohort study.

PARTICIPANTS: Patients with dPED in the setting of AMD.

METHODS: This observational study analyzed OCT biomarkers to assess the dPED lifecycle and identify features predictive of macular complications. Seventy-one eyes with dPED from 51 patients were reviewed over an average follow-up of 37.5 ± 17.6 months (range: 24-104), examining structural alterations via multimodal imaging, which included color fundus photography, fundus autofluorescence, and OCT, while fluorescein angiography, indocyanine green angiography, or both were performed as needed. Associations between baseline biomarkers and macular complications were assessed using Cox proportional hazard models with a frailty term to account for intereye correlation. The Fine-Gray model was used to account for competing risk analysis.

MAIN OUTCOME MEASURES: Incidence and time to development of macular complications (MNV and GA) and their associations with baseline OCT biomarkers (cuticular drusen, hyperreflective foci, external limiting membrane/ellipsoid zone integrity, and retinal pigment epithelium [RPE] hypertransmission), modeled with frailty-adjusted Cox proportional hazards and Fine-Gray competing risks; secondary measures included dPED lifecycle features (collapse, timing) and morphometrics (height, width, volume).

RESULTS: Key findings included a 39.4% incidence of dPED collapse, with 60.7% of cases progressing to complications postcollapse. In the multivariable Cox proportional model, cuticular drusen (hazard ratio [HR]: 3.8, 95% confidence interval [CI]: 1.62-9.2, P = 0.002) and the presence of hyperreflective foci (HRF) at baseline (HR: 6.6, 95% CI: 1.97-22, P = 0.02) represented the main prognostic indicators of macular complications. In the Fine-Gray competing risks analysis, cuticular drusen remained a significant independent predictor (subdistribution hazard ratio [sHR] = 18.1, 95% CI: 1.89-174, P = 0.01) of MNV development, while HRF (sHR = 6.69, 95% CI: 1.98-22.61, P = 0.002) and external limiting membrane disruption at baseline (sHR = 3.69, 95% CI: 1.03-13.14, P = 0.044) were factors significantly associated with increased GA risk.

CONCLUSIONS: These results underscore the prognostic relevance of specific imaging biomarkers in dPED. Recognizing these features early may support timely treatment and help prevent irreversible photoreceptor and RPE damage.

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

@article {pmid41377064,
year = {2026},
author = {Rathi, S and Didangelos, A and Pisarenka, S and Green, R and Zafeiri, S and Emery-Billcliff, P and Patel, N and Whalley, P and Zamiri, P and Tilakaratna, V and Szula, E and Hasan, R and Munye, MM and Unwin, RD and Bishop, PN and Keefe, D and Clark, SJ},
title = {CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1).},
journal = {Ophthalmology science},
volume = {6},
number = {1},
pages = {100980},
pmid = {41377064},
issn = {2666-9145},
abstract = {PURPOSE: Preclinical evaluation of a novel gene therapy called CTx001 for treating geographic atrophy (GA). CTx001 encodes a protein called mini-CR1, which is a soluble fragment of complement receptor 1.

DESIGN: CTx001 was used in vitro and in vivo to analyze expression and complement-modulating activity. Mini-CR1 was used in vitro to analyze complement-modulating activity, and its ability to cross human Bruch's membrane was evaluated ex vivo.

PARTICIPANTS: CTx001, which is a self-complementary rAAV2 gene therapy vector expressing mini-CR1. Recombinant mini-CR1 protein, retinal pigment epithelium (RPE) cell lines, serum, human donor Bruch's membrane, and a rat model.

METHODS: Recombinant mini-CR1 protein was produced in mammalian cells and purified. C3b and C4b breakdown assays were performed. Wieslab assays measured complement regulatory activity in serum. Mini-CR1 binding to C3b was measured using biolayer interferometry. The diffusion of mini-CR1 across human Bruch's membrane was assessed using an Ussing chamber. Retinal pigment epithelium cell lines were transduced with CTx001 to assess expression, including directionality and complement modulatory activity. In vivo efficacy of CTx001 was tested using a rat laser-induced choroidal neovascularization (CNV) model.

MAIN OUTCOME MEASURES: C3b/iC3b/C4b degradation, inhibition of membrane attack complex (MAC) formation in human serum, mini-CR1 binding to C3b, vector transduction efficiency, protein secretion and localization, and complement inhibition in vivo.

RESULTS: Mini-CR1 demonstrated potent cofactor activity for factor I-mediated cleavage of C3b, iC3b, and C4b; therefore, it inhibits both the alternative and classical complement pathways. It inhibited complement activation with an IC50 of 125 nM in human serum. Mini-CR1 demonstrated high-affinity binding to C3b. The mini-CR1 protein diffused across human Bruch's membrane and retained activity postdiffusion. CTx001-transduced RPE cells secreted mini-CR1 apically and basolaterally, leading to reduced C3 activation and MAC deposition. In rats, subretinal administration of CTx001 resulted in a 75.4% reduction in MAC deposition in CNV lesions (P < 0.01).

CONCLUSIONS: CTx001 is a potent inhibitor of complement. It efficiently transduces RPE cells, resulting in apical and basolateral secretion and crosses Bruch's membrane, so it is expected to deliver mini-CR1 to the retina and choroid. These findings support its further development as a 1-time gene therapy for addressing complement overactivation in GA.

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