@article {pmid41943786,
year = {2026},
author = {Aldaher, KE and Azmeh, A and Wehby, B and Alhalabi, N},
title = {Retinal Angiomatous Proliferation and Pachychoroid: A Case Report.},
journal = {Cureus},
volume = {18},
number = {3},
pages = {e104749},
pmid = {41943786},
issn = {2168-8184},
abstract = {Retinal angiomatous proliferation (RAP), also known as type 3 macular neovascularization (MNV), is a distinct and less common subtype of neovascular age-related macular degeneration (nAMD). This condition is typically associated with a thinner subfoveal choroid than in age-matched control eyes. However, the coexistence of RAP and pachychoroid, which is characterized by increased choroidal thickness and choriocapillaris attenuation, is rarely documented in the literature. In this report, we present the case of a 56-year-old male patient diagnosed with RAP in conjunction with pachychoroid. This case highlights the importance of multimodal imaging techniques, including optical coherence tomography (OCT), fluorescein angiography (FA), and optical coherence tomography angiography (OCT-A), to achieve a comprehensive assessment. Additionally, we emphasize the need for a thorough differential diagnosis to accurately identify and manage such overlapping retinal disorders. We hypothesize that choroidal ischemia secondary to compression of choriocapillaris by choroidal pachyvessels led to outer retinal ischemia and upregulation of vascular endothelial growth factor (VEGF), which caused RAP formation starting at the level of retinal superficial and deep capillary plexus and extended to the outer retina. Thus, our hypothesis supports that choriocapillaris atrophy is a common pathology between these two entities and may explain their coexistence.},
}

@article {pmid41944257,
year = {2026},
author = {Alshaikhsalama, A and Thompson, K and Hashim, H and Patel, KG},
title = {Analyzing the association between age-related macular degeneration, retinal vascular occlusions, and dementia.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261438587},
doi = {10.1177/11206721261438587},
pmid = {41944257},
issn = {1724-6016},
abstract = {PurposeTo investigate the association between age-related macular degeneration (AMD), retinal artery occlusion (RAO), and retinal vein occlusion (RVO) and the future development of Alzheimer's disease (AD), vascular dementia (VaD), and all-cause dementia (ACD).MethodsRetrospective propensity score-matched cohort study using TriNetX, a confederated healthcare network. The study population included 91,296 AMD, 15,372 RAO, 35,862 RVO, and 3,076,291 population control (PC) patients aged 65 and older. Propensity score matching was applied to control for baseline demographics and health characteristics. The primary outcome was the measured risk of developing AD, VaD, and ACD following incident diagnosis of AMD, RAO, or RVO.Major FindingsAMD was associated with a significantly elevated risk of AD (HR, 1.25; 95% CI, 1.17-1.34; P < 0.001), VaD (HR, 1.20; 95% CI, 1.11-1.31; P < 0.001), and ACD (HR, 1.12; 95% CI, 1.08-1.16; P < 0.001) following diagnosis with an average follow up of 45.0 ± 36.7 months. RVO patients also displayed higher risks across all dementia types (AD: HR, 1.46; 95% CI, 1.22-1.74; P < 0.001; VaD: HR, 1.51; 95% CI, 1.23-1.87; P < 0.001; ACD: HR, 1.34; 95% CI, 1.22-1.47; P < 0.001) with an average follow up of 46.6 ± 37.9 months.ConclusionsRetinal disease diagnoses may correlate with increased dementia risk. While AMD and RVO are associated with all dementias (AD, VaD, and ACD), RAO did not increase dementia risk.},
}

@article {pmid41944542,
year = {2026},
author = {Francis, JH and Abramson, DH},
title = {Ocular Glymphatic System: Its Modulation and Role in Intraocular Tumors.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {11},
doi = {10.1167/iovs.67.4.11},
pmid = {41944542},
issn = {1552-5783},
mesh = {Humans ; *Glymphatic System/physiology/physiopathology ; *Eye Neoplasms/physiopathology ; Animals ; Glaucoma/physiopathology ; },
abstract = {The glymphatic system is a glial-based perivascular network that clears metabolic waste from the central nervous system (CNS), and its dysfunction is related to neurodegenerative disease. This review describes a correlate ocular glymphatic system in the eye and describes how this might relate to ophthalmic diseases. This review article summarizes the published literature on the CNS and ophthalmic glymphatic system and how its dysfunction relates to disease. There are associations in the pathogenesis among neurodegeneration, glaucoma, and age-related macular degeneration (AMD), which could be explained through glymphatic dysfunction in the CNS and eye, respectively. The protective effects of exercise and sleep further demonstrate associations among neurodegeneration, glaucoma, and AMD. We provide new insights on the role of the glymphatic system and intraocular tumors, proposing that tumors may hijack the glymphatic system as a bidirectional pathway of communication between the eye and the brain. New therapies for enhancing CNS glymphatic flow are discussed. Dysfunction of the glymphatic system may be a unifying pathogenesis among neurodegeneration, glaucoma, and AMD. Future research should analyze whether CNS-focused therapeutics may improve ocular disease. The role of the glymphatic system in the pathogenesis of intraocular tumors warrants further investigation.},
}

Humans
*Glymphatic System/physiology/physiopathology
*Eye Neoplasms/physiopathology
Animals
Glaucoma/physiopathology

@article {pmid41944612,
year = {2026},
author = {Jacob, N and Chhablani, J and Chandra Behera, U and Narayanan, R and Sahoo, NK},
title = {Large and medium choroidal vessel remodelling in progressive age-related macular degeneration and polypoidal choroidal vasculopathy.},
journal = {Retinal cases & brief reports},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICB.0000000000001925},
pmid = {41944612},
issn = {1937-1578},
abstract = {PURPOSE: To describe the long-term follow-up of large and medium-sized choroidal vessels in eyes with age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV).

METHODS: This was a retrospective, observational analysis of eyes with AMD or PCV, with a minimum of five years of follow-up of indocyanine green angiography (ICGA). Qualitative analysis of the choroidal vessels was carried out at baseline until the final visit.

RESULTS: We analysed ten eyes of five patients diagnosed with either AMD or PCV with a follow-up duration ranging from seven to sixteen years. Eyes with active disease received various treatment modalities. On serial follow-up of ICGA images, remodelling of medium and large choroidal vessels was seen. The changes included large choroidal vessel attenuation, prominence/ dilatation of pre-existing choroidal vessels connecting the neovascular complex and formation of new anastomotic channels. These changes appeared adjacent to present or future neovascular complex locations. One uninvolved fellow eye showed minimal changes on follow-up.

CONCLUSION: We report the long-term changes in large and medium-sized choroidal vessels in eyes with AMD and PCV with serial ICGA images. These vascular alterations suggest the possible role played by these vessels in the pathogenesis of choroidal neovascular complexes.},
}

@article {pmid41937714,
year = {2026},
author = {Samman, M and Khan, H and Aziz, AA and Patel, R and Khanani, AM},
title = {An update on the port delivery system with ranibizumab for retinal diseases.},
journal = {Expert opinion on drug delivery},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/17425247.2026.2652029},
pmid = {41937714},
issn = {1744-7593},
abstract = {INTRODUCTION: Age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME) are among the leading causes of irreversible vision loss globally. Anti-vascular endothelial growth factor (VEGF) therapeutics have revolutionized the treatment and management of retinal vascular diseases. Management of these retinal diseases is highly individualized, with treatment intervals ranging from 4 to 16 weeks. The port-delivery system (PDS) with ranibizumab is a refillable implant that has demonstrated safety and efficacy while also improving treatment burden by decreasing the need for frequent injections.

AREAS COVERED: Multiple FDA-approved therapeutics are available to physicians for treating and managing retinal diseases. The ultimate goal is to achieve optimal visual and anatomic outcomes while also ensuring individualized treatment. A literature search was conducted across PubMed, Google Scholar, and pharmaceutical companies' websites from 2005 to December 2025 to review clinical data, highlight the utility of the PDS, and detail the improved structure following the voluntary class III recall.

EXPERT OPINION: The PDS provides a medium to maintain treatment of retinal vascular disease over an extended period of time. Although physicians may feel hesitant to implant the device, refinements in surgical technique and the refill-exchange procedure, along with improvements to the device, may encourage more clinical uptake of PDS in appropriate patients.},
}

@article {pmid41939091,
year = {2026},
author = {Hossain, B and Rahmatullah, S and Ahmed, T},
title = {Efficacy of brolucizumab and ranibizumab in diabetic macular edema and neovascular age-related macular degeneration: insights from a case series.},
journal = {Annals of medicine and surgery (2012)},
volume = {88},
number = {4},
pages = {2477-2483},
pmid = {41939091},
issn = {2049-0801},
abstract = {BACKGROUND: The effectiveness of various anti-vascular endothelial growth factors in treating patients with diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) in Bangladesh lacks comprehensive information.

OBJECTIVE: We evaluated the efficacy of brolucizumab and ranibizumab and assessed the incidence of drug-related adverse events in nAMD and DME patients of Bangladesh.

METHODS: In this retrospective case series, 20 patients who had received either intravitreal brolucizumab (n = 10) or ranibizumab (n = 10) were included. Demographic and clinical characteristics, data on best-corrected visual acuity (BCVA), and optical coherence tomography (OCT) measurements, including macular volume (MV) and central subfield retinal thickness (CSRT), were recorded for each patient at baseline and follow-up visits. In addition, brolucizumab was compared with ranibizumab in terms of above mentioned parameters.

RESULTS: Both brolucizumab and ranibizumab induced changes in patient parameters, including BCVA, OCT measurements, and MV, relative to baseline values. At the 12-week follow-up, neither drug demonstrated statistically significant superiority over the other (P > 0.05 in all cases). However, over the course of treatment, the mean BCVA showed a significant improvement following the initiation of brolucizumab therapy (P = 0.042). In terms of OCT findings, the mean CSRT significantly decreased from 508.5 ± 101.1 µm at baseline to 241 ± 40.4 µm at week 12, while the mean MV was significantly reduced from 10.3 ± 1.0 mm[3] to 8.2 ± 1.6 mm[3] (P < 0.05).

CONCLUSION: Intravitreal brolucizumab appeared to be an effective option for patients with nAMD and DME.},
}

@article {pmid41941161,
year = {2026},
author = {Yuan, R and Zhang, Y and Liu, Z and Xu, P and Li, K},
title = {A Study of the Causal Association Between Autoimmune Diseases and Blinding Eye Diseases.},
journal = {Current medicinal chemistry},
volume = {},
number = {},
pages = {},
doi = {10.2174/0109298673409616260128140543},
pmid = {41941161},
issn = {1875-533X},
abstract = {INTRODUCTION: Autoimmune diseases (ADs) are known to affect multiple organs, including the eyes. This study aims to evaluate the causal associations of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) with cataracts, age-related macular degeneration (AMD), and glaucoma using Mendelian randomization (MR).

METHODS: Genome-wide association study (GWAS) data were utilized to identify single- nucleotide polymorphisms (SNPs) strongly associated with AS, SLE, RA, cataracts, AMD, and glaucoma, which served as instrumental variables (IVs). The basic analysis was performed via inverse variance weighting (IVW), complemented by weighted median (WM), MR-Egger regression, weighted mode, simple mode, and MR-Robust Adjusted contour scoring technique (RAPS). The Cochran Q test, MR-Egger intercept test, MR-Steiger test, leave-one-out analysis, funnel plot, and MR-PRESSO model were used to assess the robustness of doing sensitivity analysis.

RESULT: IVW estimated that primary angle-closure glaucoma (PACG) (OR=1.265), AMD (OR=1.063), DRY-AMD (OR=1.088), and cataracts were significantly related to RA. SLE is associated with drug-induced cataract (OR=1.113) and senile cataract (OR=1.012). AS is being linked with glaucoma (OR=1.265), PACG (OR=2.436), and primary open-angle glaucoma (POAG) (OR=1.400).

DISCUSSION: RA, SLE, and AS can directly contribute to the development of cataracts, AMD, and glaucoma. These results endorse the interdisciplinary interventions approach that can incorporate rheumatology and ophthalmology. All investigations were restricted to individuals of European descent. These findings should be verified and expanded by performing multi-ethnic studies.

CONCLUSION: The study is generally reliable in establishing the causal relationship between AS, SLE, RA, and selective blinding eye illnesses, with the rationale of applying clinical screening techniques and specific intervention strategies.},
}

@article {pmid41941273,
year = {2026},
author = {Park, JH and Liu, RJY and Sun, X and Mahalingan, KK and Hiriyanna, S and Li, T and Roll-Mecak, A},
title = {Insights into retinal disease and non-tubulin glutamylation from a RPGR-TTLL5 complex structure.},
journal = {The Journal of cell biology},
volume = {225},
number = {6},
pages = {},
doi = {10.1083/jcb.202508020},
pmid = {41941273},
issn = {1540-8140},
support = {ZIAEY000490/NH/NIH HHS/United States ; 1ZIANS003163/NS/NINDS NIH HHS/United States ; },
mesh = {Humans ; Animals ; *Eye Proteins/metabolism/chemistry/genetics ; Mice ; Crystallography, X-Ray ; Mutation ; *Retinitis Pigmentosa/genetics/metabolism ; *Peptide Synthases/metabolism/chemistry/genetics ; Protein Binding ; Models, Molecular ; Tubulin/metabolism ; },
abstract = {Mutations in retinitis pigmentosa GTPase regulator (RPGR) cause photoreceptor degeneration, vision loss, and eventual blindness. RPGR function requires glutamylation by tubulin tyrosine ligase-like 5 (TTLL5) whose mutation is also linked to severe forms of retinal degeneration. How TTLL5 targets RPGR and how mutations in either protein cause disease are unknown. Here we report the 2.8-Å X-ray crystal structure of the coactivator interacting domain (CID) of human TTLL5 in complex with the RPGR C terminus, both required for glutamylation. The RPGR C terminus forms a helix that intercalates through aromatic interactions into the CID helical bundle of novel fold. Interfacial residues are mutated in retinitis pigmentosa, as well as macular degeneration of unknown etiology. Key mutations at this interface abolish RPGR-TTLL5 interaction in vitro and RPGR glutamylation in mouse photoreceptors. Our work reveals mechanisms of non-tubulin substrate recognition by TTLL glutamylases, increasingly recognized as broad regulators of the proteome, and sheds light on mechanisms of disease associated with TTLL5 and RPGR mutations.},
}

Humans
Animals
*Eye Proteins/metabolism/chemistry/genetics
Mice
Crystallography, X-Ray
Mutation
*Retinitis Pigmentosa/genetics/metabolism
*Peptide Synthases/metabolism/chemistry/genetics
Protein Binding
Models, Molecular
Tubulin/metabolism

@article {pmid41941952,
year = {2026},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Can Gene Therapy Revolutionize Treatment of Neovascular Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.04.001},
pmid = {41941952},
issn = {1879-1891},
abstract = {TOPIC: This systematic review and meta-analysis (PROSPERO: CRD42024619992) evaluated whether gene therapy provides safe and clinically meaningful efficacy for patients with neovascular age-related macular degeneration (nAMD). The clinical question addressed outcomes in patients with nAMD receiving gene therapy (primarily adeno-associated virus-based anti-VEGF constructs) compared with baseline or standard care contexts, focusing on visual acuity, anatomical response, treatment burden, and safety. Anti-VEGF intravitreal injections remain the current standard of care but require frequent administration and long-term adherence.

CLINICAL RELEVANCE: nAMD is a major cause of irreversible vision loss in older adults and imposes substantial treatment burden due to repeated injections. Gene therapy aims to achieve sustained intraocular therapeutic protein expression after a single or infrequent administration, potentially reducing injection frequency while maintaining disease control. Establishing safety and functional efficacy is critical before translation into routine retinal practice.

METHODS: Following PRISMA guidelines, databases (PubMed, Embase, Scopus, Web of Science, Google Scholar, and Cochrane Library) were searched from inception to February 1, 2026. Eligible studies were prospective interventional clinical trials evaluating gene therapy in nAMD, including randomized and early-phase dose-escalation designs. Primary outcomes included best-corrected visual acuity (BCVA), central subfield thickness (CST), rescue anti-VEGF requirement, mortality, and adverse events. Risk of bias was assessed using RoB 2 and ROBINS-I tools. Multilevel random-effects meta-analyses using restricted maximum likelihood accounted for clustering of multi-arm cohorts.

RESULTS: Eight trials (7 randomized, 1 nonrandomized) comprising 203 treated participants were included. Multilevel REML analysis showed no significant pooled BCVA improvement (MD 0.54 letters; 95% CI -7.38 to 8.46) despite favorable fixed-effect estimates. CST demonstrated significant anatomical reduction (MD 37.13 µm; 95% CI 26.63-47.62). Approximately 44% of eyes required rescue anti-VEGF injections. Safety outcomes demonstrated generally low-to-moderate event probabilities: mortality approximately 8%, serious adverse events approximately 21-38%, inflammation approximately 20%, and retinal hemorrhage approximately 12%, with negligible heterogeneity across most endpoints. Publication bias was detected for BCVA and CST but was minimal for safety outcomes.

CONCLUSION: Gene therapy for nAMD demonstrates encouraging safety and anatomical efficacy signals but lacks consistent functional visual improvement. Current evidence supports a treatment-burden-reducing adjunctive role rather than replacement of anti-VEGF therapy. Evidence strength is limited by early-phase designs, small sample sizes, and clinical heterogeneity; ongoing phase 3 trials are required to define long-term efficacy and clinical positioning.},
}

@article {pmid41943094,
year = {2026},
author = {Jorge, R and Rego, MGB and Zupelli, AS and Calado, RT},
title = {Off-label intravitreal eculizumab for geographic atrophy: report of the first two cases.},
journal = {International journal of retina and vitreous},
volume = {12},
number = {1},
pages = {},
pmid = {41943094},
issn = {2056-9920},
}

@article {pmid41935371,
year = {2026},
author = {Moftakhar-Bazkiaei, A and Farzaneh, M},
title = {Network-based Transcriptomic Profiling of Fetal Astrocyte Differentiation Reveals Therapeutic Targets for Neurodegenerative Disease.},
journal = {Current molecular medicine},
volume = {},
number = {},
pages = {},
doi = {10.2174/0115665240412373260224061022},
pmid = {41935371},
issn = {1875-5666},
abstract = {INTRODUCTION: Neurodegenerative disorders, including Alzheimer's Disease (AD), Parkinson's Disease (PD), and Age-related Macular Degeneration (AMD), are marked by the progressive loss of specific neuronal populations. Astrocytes, the glial cells surrounding neurons, play a critical role in maintaining neuronal health by providing neurotrophic support, producing antioxidants, and clearing waste. Dysfunctional astrocytes contribute to disease progression, yet their developmental trajectory and molecular regulation remain incompletely understood.

METHOD: This study aims to computationally characterize transcriptional differences between fetal astrocytes and neural stem cell lines to identify key regulatory genes, pathways, and therapeutic targets relevant to astrocyte-linked neurodegeneration. Using microarray data and bioinformatics pipelines, 359 Differentially Expressed Genes (DEGs) were identified, including 249 upregulated and 110 downregulated transcripts.

RESULTS: Protein-Protein Interaction (PPI) network analysis revealed ten hub genes- COL1A1, TIMP1, LOX, COL6A1, COL6A3, COL5A1, CD44, LTBP2, ACTA2, and PLAU-central to extracellular matrix remodeling and cell adhesion. Drug-gene interaction analysis linked these genes to compounds such as Estradiol valerate, Retinoic acid, and Calcitriol, suggesting therapeutic relevance.

DISCUSSION: Enrichment analysis highlighted transcriptional regulation, apoptosis, and ECM-receptor interaction as dominant biological themes. Key miRNA-mRNA interactions, including hsa-miR-877-5p and hsa-miR-767-5p targeting LOX and COL6A3 were also identified.

CONCLUSION: Overall, this study integrates transcriptomic profiling, network modeling, and drug-gene interaction analysis to uncover astrocyte-specific molecular targets, offering a computational framework for therapeutic exploration in neurodegenerative disease.},
}

@article {pmid41935442,
year = {2025},
author = {Chen, KY and Chan, HC and Lin, WW and Chan, CM},
title = {Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review.},
journal = {Redox biology},
volume = {93},
number = {},
pages = {103976},
doi = {10.1016/j.redox.2025.103976},
pmid = {41935442},
issn = {2213-2317},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly and has a multifactorial etiology involving advanced age, genetic susceptibility, and environmental risk factors. Accumulating evidence suggests that mitochondrial dysfunction is a central pathogenic mechanism in AMD, particularly in the retinal pigment epithelium (RPE). The RPE is critical for retinal homeostasis, and its high metabolic activity renders it vulnerable to age-related mitochondrial dysfunction. In AMD, the core processes of mitochondrial dynamics-fission, fusion, biogenesis, and mitophagy-are profoundly dysregulated, leading to a fragmented and dysfunctional mitochondrial network. This failure of quality control results in bioenergetic deficits, excessive oxidative stress, and the release of damage-associated molecular patterns that fuel chronic inflammation and complement-mediated damage. Experimental models and human tissue studies have strengthened the link between mitochondrial dysfunction and AMD pathology, revealing structural abnormalities, mitochondrial DNA (mtDNA) damage, and altered metabolic signatures. Therapeutic strategies targeting mitochondrial pathways, including mitochondria-targeted antioxidants, dynamic modulators, and enhancers of biogenesis and mitophagy, such as agents that restore defective mitophagosome formation, represent promising avenues for intervention. As the field advances, the integration of biomarker development and personalized approaches holds the potential to transform the clinical landscape of AMD by addressing the root causes of cellular dysfunction.},
}

@article {pmid41936183,
year = {2026},
author = {Ju, Y and Lu, H and Liu, S and Chen, X and Ni, N and Su, Y and Liu, Y and Zhang, D and Chen, M and Huang, R and Zhang, J and Xiang, H and Chen, Y and Tang, Z and Gu, P},
title = {Molybdenum-based antioxidative nanomedicine fighting against retinal pigment epithelium degeneration.},
journal = {Biomaterials},
volume = {333},
number = {},
pages = {124192},
doi = {10.1016/j.biomaterials.2026.124192},
pmid = {41936183},
issn = {1878-5905},
abstract = {Oxidative stress-induced retinal pigment epithelium (RPE) degeneration is the pathologic basis of most retinal degenerative diseases, especially dry age-related macular degeneration (AMD), for which corresponding therapeutic strategies currently were still in their infancy and lack optimal efficacy. In the present study, cerium-doped molybdenum-based polyoxometalate (MoCe) nanoclusters (NCs) are designed as antioxidative nanocatalysts to inhibit oxidative stress-induced RPE degeneration and subsequent retinal damage. The synthesized MoCe NCs display prominent reactive oxygen species (ROS) scavenging efficacy with excellent in vivo biocompatibility. In RPE degeneration mice model, a single intravitreal administration of MoCe NCs effectively inhibit RPE oxidative degeneration and substantially protect retinal structure and visual function. Upon high-throughput sequencing combined with bioinformatics analysis, MoCe administration predominantly restores the expression of DNA repair-related genes and inhibits oxidative stress-induced apoptosis by suppressing the JNK/c-Jun signaling pathway. The ideal biocompatibility and remarkable protective effect render MoCe NCs as the promising nanomedicines combating RPE degeneration-associated retinal diseases especially AMD.},
}

@article {pmid41936993,
year = {2026},
author = {Lizard, G and Sassi, K and Mackrill, JJ and Ghzaiel, I and Meziane, S and Hassen, E and Abdelkarim, M and Masmoudi-Kouki, O and Ghrairi, T and Brahmi, F and Gargouri, A and Rezig, L and Benkalifa, R and Khallouki, F and El Midaoui, A and Pincemail, J and Atanasov, AG and Vejux, A and Millot, N},
title = {7-ketocholesterol as a theranostic target: potential applications and future perspectives.},
journal = {Chemistry and physics of lipids},
volume = {},
number = {},
pages = {105588},
doi = {10.1016/j.chemphyslip.2026.105588},
pmid = {41936993},
issn = {1873-2941},
abstract = {7-Ketocholesterol (7KC) is mainly formed by cholesterol autoxidation and is a pro-oxidant and pro-inflammatory bioactive lipid that also induces different types of cell death, including oxiapoptophagy. It is frequently associated with major age-related diseases, such as cardiovascular diseases, age-related macular degeneration, and Alzheimer's disease. 7KC can therefore be considered a biomarker for these diseases, offering the possibility of developing theranostic strategies combining diagnosis and treatment. Currently, all the elements are in place to develop tools for the design of theranostic therapies targeting 7KC in diseased organs: antibodies, nanoparticles used as nanoplatforms, molecules that neutralize 7KC such as enzymes which degrade it, as well as natural or synthetic compounds that inhibit the cytotoxic signaling pathways associated with oxidative stress, inflammation and cell death activated by 7KC. Identifying and neutralizing 7KC biological activities using a theranostic approach could also be of interest for growing medical fields such as space medicine widely concerned by oxidative stress, aging and age-related diseases, driven by microgravity. This review supports that most of key tools are now available to develop theranostic treatments targeting 7KC in age-related pathologies, especially in cardiovascular diseases associated with atheroma, but also in age-related macular degeneration and Alzheimer's disease. Discovery of effective treatments for these diseases is a major challenge and will answer an important need for both patients and caregivers.},
}

@article {pmid41937011,
year = {2026},
author = {Bagewadi, S and Parameswaran, S and Sethuraman, S and Subramanian, A},
title = {Hyaluronic acid-poly (vinyl alcohol) composite hydrogels with self-assembled peptide nanofibers as Bruch's membrane mimics for age-related macular degeneration treatment.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {151748},
doi = {10.1016/j.ijbiomac.2026.151748},
pmid = {41937011},
issn = {1879-0003},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the elderly, and effective curative therapies are not available. This study presents a tissue-engineering strategy for retinal regeneration using an injectable, in situ-forming hydrogel composed of thiol-functionalized hyaluronic acid (HA-SH) and polyvinyl alcohol (PVA), reinforced with peptide nanofibers. Decellularized Bruch's membrane derived from goat eyes was used as a control and exhibited a fiber diameter of 75.09 ± 12.99 nm, thickness of 6.26 ± 1.12 μm, and hydrophilic properties (contact angle: 39.46° ± 0.46). In comparison, the GAGA-YIGSR-based hydrogel membrane demonstrated comparable structural features with a fiber diameter of 92.38 ± 16.37 nm, a thickness of 13.43 ± 3.64 μm, and a contact angle of 72.13° ± 2.98. The HA-SH/PVA hydrogel incorporating peptide nanofibers significantly enhanced retinal pigment epithelium (RPE) cell viability, adhesion, proliferation, phagocytosis, and RPE-specific gene expression compared to the peptide-free hydrogel. In vivo functional evaluation using H&E-stained retinal sections revealed that the HA-SH/PVA hydrogel containing the GAGA-YIGSR peptide markedly improved RPE cell organization, ONL nuclei density (1578.22 ± 187.03), ONL cell rows (9.02 ± 1.74), linear RPE cell count (10.6 ± 2.6), and ONL thickness (35.52 ± 4.44 μm) relative to saline controls. Furthermore, the hydrogel preserved retinal barrier integrity and ultrastructural parameters, including tight-junctions, subretinal pigment epithelium space (7.26 ± 4.92 μm), BM thickness (5.91 ± 1.07 μm), collagen area (21.74 ± 3.48%), collagen thickness (81.8 ± 24.17 μm), and collagen pore area (17.72 ± 9.19%), which were comparable to those of healthy controls. In conclusion, this study successfully developed and evaluated an injectable peptide-functionalized hydrogel as a promising therapeutic scaffold for retinal tissue regeneration in AMD.},
}

@article {pmid41933659,
year = {2026},
author = {von der Emde, L and Reiter, GS and Mallwitz, M and Jauch, AS and Wall, K and Holz, FG and Pollreisz, A and Ach, T},
title = {Quantitative fundus autofluorescence in age-related macular degeneration.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.03.018},
pmid = {41933659},
issn = {1879-3304},
abstract = {Fundus autofluorescence captures the fluorescence of the retina, specifically the retinal pigment epithelium (RPE). Within the RPE, fluorophores, including lipofuscin, melanolipofuscin, and melanosomes, fluoresce when excited by light of varying wavelengths. Quantitative fundus autofluorescence (QAF), which has been implemented using blue excitation light, enables mapping and quantifying lipofuscin and melanolipofuscin fluorescence. This is achieved by using a reference bar to standardize measurements. The technical functionality of QAF relies on repeatability and high image quality. Multicenter studies, however, indicate variability. Age-related lens opacities also affect QAF, necessitating individualized correction formulas for accuracy. Accordingly, this review focuses on the development and application of QAF, addressing technical considerations and its relevance to structural and cellular changes in age-related macular degeneration (AMD), and highlighting how QAF can provide clinically meaningful information for AMD diagnosis and therapy monitoring. In AMD, numerous independent studies have found reduced autofluorescence at the posterior pole and as AMD progresses autofluorescence further decreases. Typical AMD lesions, such as subretinal drusenoid deposits, have been associated with significant QAF reduction. On a cellular level, granule aggregation and degranulation are identified as histological correlates. Subcellularly, technologies like serial block-face scanning electron and structured illumination microscopy have revealed a reduced lipofuscin volumetric density and RPE dysmorphia associated with AMD's reduced autofluorescence. New software tools enhance QAF's potential for detailed lesion analysis. Future advancements in QAF include integrating new excitation wavelengths and combining quantified emission spectra and fluorescence lifetimes to improve early detection of AMD-related changes. Despite challenges, QAF continues to evolve, promising better insights into retinal health and disease.},
}

@article {pmid41934603,
year = {2026},
author = {Friedman, SM and Xu, Y and Sherman, S and Kuznik, A and Mojebi, A and Keeping, S and Chan, K and Leng, T and Patel, N},
title = {Correction: Aflibercept 8 mg versus Faricimab Treat-and-Extend for Diabetic Macular Edema or Neovascular Age-Related Macular Degeneration: A Bayesian Fixed-Effect Network Meta-analysis of Clinical Trials.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
doi = {10.1007/s40123-026-01377-2},
pmid = {41934603},
issn = {2193-8245},
}

@article {pmid41934654,
year = {2026},
author = {Asanad, S and Boyer, DS},
title = {Gene therapy for wet AMD: a paradigm shift in the standard of care.},
journal = {Expert opinion on emerging drugs},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728214.2026.2651330},
pmid = {41934654},
issn = {1744-7623},
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD), or wet AMD, remains a leading cause of vision loss in older adults. Current standard of care relies on repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections, which create significant treatment burdens for patients and healthcare systems. Emerging gene therapies aim to address these challenges by delivering sustained therapeutic effects via single administration.

AREAS COVERED: Next-generation gene therapies are transforming AMD treatment by enabling sustained, autonomous production of therapeutic proteins within ocular tissues, enabling the eye to synthesize its own anti-VEGF agents. A comprehensive literature search was performed using both PubMed and ClinicalTrials.gov to identify pertinent manuscripts and clinical trials for this narrative review. Keywords utilized included: Gene therapy, wet AMD, neovascular AMD, Viral Vectors, Adeno-associated viral vectors, Subretinal, Suprachoroidal, and Retinal Pigment Epithelium.

EXPERT OPINION: Advances in gene therapy for wet AMD may revolutionize treatment by enabling sustained intraocular anti-VEGF protein, reducing frequent injections, improving patient adherence, and potentially lowering long-term healthcare costs. Although promising, challenges including long-term safety, complex delivery procedures, immune responses, regulatory hurdles, and the need for optimized vectors and clinical protocols must be addressed before widespread adoption and integration into standard care.},
}

@article {pmid41935142,
year = {2026},
author = {Mehta, H},
title = {Social deprivation in neovascular age-related macular degeneration: when equal treatment does not deliver equal vision.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41935142},
issn = {1476-5454},
}

@article {pmid41929012,
year = {2026},
author = {Navratil, EM and Liu, X and Wiley, LA and Anderson, MG and Meyer, KJ and Brown, RF and Evans, IA and Taylor, EB and Stone, EM and Tucker, BA and Mullins, RF},
title = {Metabolic Analysis of Human Retinal Pigment Epithelium and Choroid Tissue in Aging and Macular Degeneration.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.24.713982},
pmid = {41929012},
issn = {2692-8205},
abstract = {Age-related macular degeneration is a common ocular disease that causes vision loss in the elderly, with a complex set of risk factors and proposed mechanisms of pathogenesis. A powerful method for investigating changes in disease is metabolomics, by which small molecules can be identified and quantified simultaneously. We report here the metabolic analysis of human RPE-choroid tissue in aging and macular degeneration (AMD), as well as comparisons of human macular and extramacular RPE-choroid and neural retina. Levels of 215 metabolites were determined in young donors, AMD donors (early/intermediate, geographic atrophy, and neovascularization) and age-matched controls. The largest number of metabolite differences were observed between young and healthy aged controls, as opposed to between aged controls and any stage of AMD. Two notable metabolites found to be increased in aging choroids are trimethylamine N-oxide and uric acid, both of which were significant after Bonferroni correction. A mouse endothelial cell line treated with a high concentration of uric acid exhibited reduced migration in a wound closure assay. This study provides initial insights into the metabolome of human choroids in varying states of age and macular degeneration, as well as functional implications of these changes in the aging choroid.},
}

@article {pmid41929144,
year = {2026},
author = {Mir, HA and Mahesh, G and Palanimuthu, A and Cioffi, CL and Petrukhin, K},
title = {Loss of Lamp2a-dependent chaperone-mediated autophagy drives dry AMD-like retinal pathology in mice and is rescued by BK channel activation.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.19.712761},
pmid = {41929144},
issn = {2692-8205},
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in elderly individuals for which no effective treatments are currently available. The photoreceptor loss in dry AMD is secondary to the demise of the retinal pigment epithelium (RPE) cells. The accumulation of extracellular deposits, known as drusen, resulting in part from deficient lysosomal and autophagosomal degradation, is a key feature of dry AMD pathogenesis. Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that maintains proteostasis by targeting specific cytosolic proteins for lysosomal translocation and degradation. LAMP2A (lysosome-associated membrane protein 2A) functions as the key lysosomal receptor required for CMA. Using Lamp2a knockout mouse, we show that selective CMA dysfunction recapitulates AMD-like pathologies, including sub-RPE lipid and protein deposits, RPE atrophy, Bruch's membrane thickening, and impaired autophagic activity. Furthermore, we identify large-conductance Ca[2+]-activated K[+] (BK) channels as a therapeutic target for restoring autophagic activity. Mechanistically, pharmacological activation of BK channels with the small-molecule agonist GLA-1-1 enhances macroautophagy and stimulates autophagic flux by promoting autophagosome-lysosome fusion. Importantly, oral administration of GLA-1-1 in markedly attenuates structural, functional, and molecular retinal abnormalities in Lamp2a -deficient mice, suggesting that pharmacological activation of macroautophagy through facilitating autophagosome-lysosome fusion can partially compensate for CMA deficiency. Together, these findings demonstrate that pharmacological activation of macroautophagy can ameliorate the retinal phenotype resulting from CMA dysfunction and support BK channel activation by GLA-1-1 as a promising therapeutic strategy for dry AMD.},
}

@article {pmid41929345,
year = {2026},
author = {Chau, K and Allison, K and Braithwaite, T and Harley, ITW and Hassman, LM},
title = {Genomic network analysis links uveitis with systemic inflammatory diseases.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.24.26349228},
pmid = {41929345},
abstract = {OBJECTIVE: To determine whether uveitis shares genetic similarity with extraocular immune-mediated inflammatory diseases (IMIDs), we performed network analysis of putative causal genes associated with ocular inflammatory disease, IMIDs and eye-specific diseases, including age-related macular degeneration and monogenic disorders.

METHODS: We identified putative causal genes for genome-wide significance variants from uveitis, IMIDs and ocular diseases using OpenTargets and published studies. To assess the gene-level pleiotropy between disease groups, we quantified the causal gene overlap between groups, and the Jaccard Similarity Indices for individual disease pairs. We then used a network approach to assess the molecular genetic similarity between diseases at a biological pathway level and comparative statistics to identify diseases with greater network similarity to uveitis.

RESULTS: Seventy-five percent of the putative causal genes for uveitis are also causal for IMIDs, while no uveitis genes are shared with primary ocular disorders. Network analysis revealed that 1) uveitis genes are more closely networked with systemic IMIDs disease genes than with ocular-specific disease genes; and 2) significant network similarity links uveitis and specific IMIDs, such as ankylosing spondylitis and sarcoidosis.

CONCLUSIONS: Overlapping causal genes and network similarity indicate that uveitis is predominantly an inflammatory disease, sharing genetic architecture with other IMIDs. Future studies aimed at dissecting genetic heterogeneity within uveitis may determine whether subgroups share common immune pathways that could nominate endotype-specific therapeutic approaches.},
}

@article {pmid41931001,
year = {2026},
author = {Easton, CA and Wilmarth, PA and Criss, M and Kim, K and Reddy, AP and Tanne, S and Boone, JQ and Tran, KD},
title = {Comparison of Transcript and Protein Abundance in Human Donor Retinas Support Extending Postmortem Interval From 12 to 18 Hours to Expand the Donor Pool for Biomedical Research.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {4},
pages = {9},
doi = {10.1167/iovs.67.4.9},
pmid = {41931001},
issn = {1552-5783},
mesh = {Humans ; *Tissue Donors ; Proteomics/methods ; *Retina/metabolism ; Female ; *Eye Proteins/genetics/metabolism ; Middle Aged ; Male ; Aged ; *Biomedical Research ; *Postmortem Changes ; Adult ; Tandem Mass Spectrometry ; Time Factors ; Organ Preservation/methods ; *RNA, Messenger/genetics ; },
abstract = {PURPOSE: To evaluate whether extending the postmortem interval (PMI) from 12 to 18 hours affects transcript and protein abundances in the human retina.

METHODS: Donor eyes were recovered from postmortem donors (n = 7 pairs) and stored at 2°C-8°C. Only donor eyes with ocular cooling within eight hours of death were examined. The OD retina was preserved at 12 hours and the OS retina at 18 hours postmortem. Retinas were flash frozen with liquid nitrogen. The macular region superior to the fovea was used for RNA sequencing (RNA-seq), whereas the inferior region was processed for tandem mass tag (TMT) quantitative proteomics. RNA library preparations were performed simultaneously, and the sequencing of all samples were conducted on the same chip. Proteins were isolated and labeled with 16-plex TMTPro isobaric tags, and all samples were analyzed in a 20-fraction TMT-mass spectrometry experiment. RNA-seq data were processed using DESeq2 (Bioconductor) and proteomic data were analyzed using the previously published PAW pipeline.

RESULTS: RNA-seq identified 22,446 transcripts, with only five transcripts showing significant differential expression (adjusted P < 0.1 and a Log2FoldChange > 1) between 12 and 18 hours. No enriched pathways were associated with these changes. Proteomic analysis identified 6,109 proteins, with no significant differences in abundance (all adjusted P > 0.05). Retinal cell-type specific markers and markers relevant for disease research, such as age-related macular degeneration and glaucoma, remained stable across both time points.

CONCLUSIONS: Extending the PMI cutoff from 12 to 18 hours did not significantly impact transcriptomic or proteomic integrity in human donor retinas. This PMI extension greatly increases the availability of donor eyes for biomedical research.},
}

Humans
*Tissue Donors
Proteomics/methods
*Retina/metabolism
Female
*Eye Proteins/genetics/metabolism
Middle Aged
Male
Aged
*Biomedical Research
*Postmortem Changes
Adult
Tandem Mass Spectrometry
Time Factors
Organ Preservation/methods
*RNA, Messenger/genetics

@article {pmid41932376,
year = {2026},
author = {Cui, X and Hui, J and Han, Q},
title = {Traffic Noise, Air Pollution, and Greenness in Relation to Age-Related Macular Degeneration: Evidence from a Cross-National Cohort Study.},
journal = {Environmental pollution (Barking, Essex : 1987)},
volume = {},
number = {},
pages = {128042},
doi = {10.1016/j.envpol.2026.128042},
pmid = {41932376},
issn = {1873-6424},
abstract = {Age-related macular degeneration (AMD) is influenced not only by biological factors but also by the broader urban environment, yet evidence integrating multiple environmental exposures remains limited. We examined the associations of residential road traffic noise, fine particulate air pollution (PM2.5), and green space with AMD risk using data from the UK Biobank (207,859 controls and 5,571 incident AMD cases) and an independent hospital-based cohort from Tianjin, China (286 controls and 233 cases). Environmental exposures were assessed using harmonized metrics, and associations were estimated using Cox proportional hazards models in the UK Biobank and multivariable logistic regression in the Tianjin cohort. Restricted cubic splines were applied to evaluate non-linear exposure-response relationships, and joint exposure analyses assessed combined environmental effects. Higher levels of Lden, Lnight, and PM2.5 were consistently associated with increased AMD risk, whereas greater residential green space was associated with lower risk across both cohorts. Non-linear analyses revealed steep risk increases at moderate-to-high noise and PM2.5 levels and a J-shaped association for green space. Individuals exposed to both high noise and high PM2.5 exhibited the greatest risk. Feature selection using Boruta and LASSO identified environmental exposures alongside age, C-reactive protein, and HbA1c as key predictors. Machine-learning models integrating environmental exposures with inflammatory and metabolic biomarkers achieved good discrimination (XGBoost AUC = 0.81). Quantile g-computation further indicated that the combined burden of urban environmental exposures was strongly associated with AMD risk, with traffic noise contributing the largest share of the mixture effect. These findings suggest that traffic noise and air pollution are important, potentially modifiable environmental risk factors for AMD, while residential green space may help mitigate risk.},
}

@article {pmid41932381,
year = {2026},
author = {Hjæresen, S and Gramkow, ET and Zhang, M and Svenningsen, ÅF},
title = {HTRA1 and Brain Disorders: A Balancing Act Across Neurodegeneration and Repair.},
journal = {Progress in neurobiology},
volume = {},
number = {},
pages = {102914},
doi = {10.1016/j.pneurobio.2026.102914},
pmid = {41932381},
issn = {1873-5118},
abstract = {High temperature requirement protein A1 (HTRA1) is a trypsin-like serine protease increasingly recognized as a central regulator of brain homeostasis. HTRA1 is broadly expressed in the brain, where it regulates proteostasis, extracellular matrix (ECM) remodeling, and important signaling pathways such as: TGF-β, Wnt, and Notch. These functions are essential for maintaining blood-brain barrier integrity, supporting tissue repair, and restraining inflammation. HTRA1 is a double-edged sword, as both insufficient and excessive activity can lead to neurodegenerative and vascular pathology. Reduced HTRA1 levels are linked to ECM accumulation and vascular fibrosis, while elevated activity contributes to tissue breakdown, inflammation, and impaired repair. This dual role is implicated in a range of disorders, including cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy, small vessel disease, age-related macular degeneration, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We review recent insights into HTRA1's interactions with ApoE and tau, its roles in lipid and cytoskeletal regulation, and its modulation by inhibitors such as: Macrophage Migration Inhibitory Factor. Finally, we explore its biomarker potential and therapeutic targeting strategies. Understanding the mechanisms behind HTRA1's shift from protective to pathological is crucial for developing targeted therapies that preserve its beneficial roles.},
}

@article {pmid41736120,
year = {2026},
author = {Xiang, Y and Zuo, G and He, X and Wang, K and Zhu, Y and Cheng, S},
title = {Therapeutic potential of mesenchymal stem cells in ocular degenerative disorders.},
journal = {Journal of translational medicine},
volume = {24},
number = {1},
pages = {},
pmid = {41736120},
issn = {1479-5876},
abstract = {BACKGROUND: Mesenchymal stem cells (MSCs), with their regenerative, anti‑inflammatory, and immunomodulatory properties, represent a promising therapeutic strategy for degenerative retinal diseases. Current treatments fail to address core pathologies-such as inflammation, oxidative stress, and apoptosis-in conditions including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, and glaucoma, underscoring the need for regenerative approaches.

METHODS: This review summarizes the signaling pathways through which MSCs and their exosomes promote tissue repair and neuroprotection in ocular disorders. It evaluates published preclinical and clinical data to outline the current therapeutic applications, efficacy, and safety profiles of MSC-based therapies in ophthalmology.

RESULTS: MSC-based interventions show potential in alleviating key pathogenic processes in retinal degeneration. Clinical trials indicate their ability to reduce inflammation, oxidative stress, and apoptotic cell death, thereby supporting retinal cell survival and function. These benefits are primarily mediated through paracrine signaling via extracellular vesicles such as exosomes.

CONCLUSION: MSCs constitute a significant advance toward retinal repair and functional restoration. However, translation of these findings is hindered by the lack of standardized and regulated treatment protocols. Future efforts should focus on establishing optimized delivery methods, safety standards, and a deeper understanding of molecular mechanisms to bridge the gap between promising experimental outcomes and reliable clinical application.},
}

@article {pmid41924198,
year = {2026},
author = {Mizuma, R and Mizuki, Y and Kamata, A and Onishi, J and Sakono, T and Suzuki, M and Mizuki, N},
title = {One-Year Real-World Outcomes of Intravitreal Aflibercept 8 mg for Neovascular Age-Related Macular Degeneration in Japan: A Multicenter Retrospective Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {596218},
pmid = {41924198},
issn = {1177-5467},
abstract = {BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has improved outcomes in neovascular age-related macular degeneration (nAMD), but treatment burden remains substantial in real-world practice. High-dose aflibercept 8 mg was developed to extend dosing intervals; however, one-year real-world evidence in Japanese patients is limited.

OBJECTIVE: To evaluate one-year real-world efficacy, durability, and safety of aflibercept 8 mg for nAMD in Japan.

METHODS: This multicenter retrospective study was conducted across five institutions in Japan and included consecutive eyes with nAMD treated with aflibercept 8 mg between April and December 2024 and followed for at least 12 months. Visual acuity (VA; logMAR) and central subfield thickness (CST) were assessed at baseline and follow-up visits. Treatment followed an individualized treat-and-extend approach; 19, 1, and 20 eyes received 1, 2, and 3 loading injections, respectively. Durability was evaluated by comparing pre-switch and 12-month dosing intervals in eyes with paired data.

RESULTS: Forty eyes (36 patients) were analyzed: 35 previously treated eyes switched to aflibercept 8 mg and 5 treatment-naïve eyes. Median baseline VA was 0.155 logMAR and CST was 284 µm. VA at 12 months did not differ significantly from baseline (Hodges-Lehmann -0.0395 logMAR; 95% CI, -0.111 to 0.0141; p = 0.148), whereas CST decreased significantly (-62.0 µm; 95% CI, -106 to -32.0; p = 0.000538). Among eyes with paired pre-switch interval data (n = 35), injection intervals increased from 8 weeks (IQR, 7-12) to 12 weeks (IQR, 8-14) at 12 months (median change +2 weeks; p = 0.00471). No ocular or systemic adverse events potentially related to aflibercept 8 mg were observed.

CONCLUSION: In this Japanese real-world nAMD cohort, significant CST reduction was observed over 12 months, while visual acuity remained stable. Longer dosing intervals were also observed after switching.},
}

@article {pmid41925707,
year = {2026},
author = {Allon, G and Sarrabia, G and Goren, L and Moisseiev, E and Segal, O},
title = {Assessing patients who are treated with intravitreal injections by ultra-wide field imaging versus slit lamp biomicroscopy.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261438854},
doi = {10.1177/11206721261438854},
pmid = {41925707},
issn = {1724-6016},
abstract = {PurposeTo evaluate the agreement between a virtual clinic model based on ultra-widefield imaging (UWFI) and spectral-domain optical coherence tomography (SD-OCT) and conventional face-to-face (F2F) slit-lamp fundus examination with SD-OCT for treatment decision-making in patients receiving intravitreal injections.MethodsIn this retrospective masked paired comparative study, consecutive patients receiving intravitreal injections underwent F2F evaluation by a retina specialist using slit-lamp biomicroscopy and SD-OCT. F2F examination was predefined as the reference standard. During the same clinical encounter, UWFI was obtained. A second retina specialist, masked to the clinical findings and decisions, independently reviewed the SD-OCT and UWFI images in a virtual setting and made management decisions.ResultsA total of 426 eyes from 304 patients were included. Of these, 217 eyes (50.94%) had neovascular age-related macular degeneration (NVAMD), 151 (35.45%) diabetic macular edema (DME), and 56 (13.15%) retinal vein occlusion (RVO; 36 branch RVO, 14 central RVO, and 6 hemi-retinal RVO). One eye (0.23%) had myopic choroidal neovascularization (CNV), and one (0.23%) had Sorsby macular dystrophy with CNV.The virtual assessment demonstrated 98.12% agreement with the F2F examination for treatment decisions (Cohen's κ = 0.90; 95% CI, 0.83-0.97). Recognition of NVAMD-associated macular hemorrhages was comparable between modalities. UWFI identified additional cases of neovascularization of the disc (NVD) and neovascularization elsewhere (NVE), all of which were subsequently confirmed on slit-lamp examination. The mean virtual review time was more than twofold shorter than the F2F evaluation (P < 0.001).ConclusionsVirtual assessment using ultra-widefield imaging demonstrated high agreement with F2F slit-lamp examination for treatment decision-making in patients receiving intravitreal injections. This approach may represent an efficient alternative for selected follow-up visits in which anterior segment evaluation is not required.},
}

@article {pmid41925898,
year = {2026},
author = {Faiz Turan, M and Ozkaya, A},
title = {Imaging biomarkers associated with visual acuity in central serous chorioretinopathy: a multimodal analysis.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {41925898},
issn = {1573-2630},
mesh = {Humans ; *Central Serous Chorioretinopathy/physiopathology/diagnosis ; *Visual Acuity/physiology ; *Tomography, Optical Coherence/methods ; Retrospective Studies ; Male ; Female ; *Fluorescein Angiography/methods ; *Multimodal Imaging/methods ; Middle Aged ; Adult ; Fundus Oculi ; Biomarkers ; Indocyanine Green/administration & dosage ; Follow-Up Studies ; Aged ; Macula Lutea/pathology ; },
abstract = {OBJECTIVE: To assess the relationship between best-corrected visual acuity (BCVA) and multimodal imaging findings including optical coherence tomography (OCT), fluorescein angiography (FA), and indocyanine green angiography (ICGA) in patients diagnosed with central serous chorioretinopathy (CSC).

METHODS AND MATERIALS: We retrospectively analyzed 249 eyes of 164 patients with CSC. OCT parameters included central macular thickness (CMT), neurosensory and pigment epithelial detachments, outer retinal integrity, and degenerative changes. FA and ICGA findings were also evaluated. Associations between multimodal imaging features and BCVA were analyzed.

RESULTS: BCVA differed significantly among CSC subgroups (p < 0.001), with the sequelae group showing the best visual acuity. CMT varied across subgroups (p < 0.001) and was negatively correlated with BCVA in the overall cohort, driven primarily by acute cases. Outer retinal alterations on OCT and angiographic markers of disease activity were associated with worse BCVA. In multivariable analysis, intraretinal and/or subretinal hyperreflective dots, cystoid macular degeneration, FA leakage, and choroidal neovascularization remained independent predictors of poorer visual acuity.

CONCLUSION: Visual acuity in CSC varies across disease subtypes and is associated with distinct OCT, FA, and ICGA features. These findings highlight the value of multimodal imaging in the assessment of visual prognosis and in supporting individualized follow-up and treatment strategies in CSC.},
}

Humans
*Central Serous Chorioretinopathy/physiopathology/diagnosis
*Visual Acuity/physiology
*Tomography, Optical Coherence/methods
Retrospective Studies
Male
Female
*Fluorescein Angiography/methods
*Multimodal Imaging/methods
Middle Aged
Adult
Fundus Oculi
Biomarkers
Indocyanine Green/administration & dosage
Follow-Up Studies
Aged
Macula Lutea/pathology

@article {pmid41927600,
year = {2026},
author = {Kim, HM and Woo, SJ},
title = {Association between screening duration and treatment outcomes in the clinical trials of ranibizumab and aflibercept for neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-41200-3},
pmid = {41927600},
issn = {2045-2322},
abstract = {The clinical implications of screening duration prior to treatment initiation in neovascular age-related macular degeneration (nAMD) are not well understood. This post hoc analysis investigated whether screening duration influences treatment outcomes in two multinational phase 3 randomized clinical trials, SB11 (ranibizumab biosimilar) and SB15 (aflibercept biosimilar), comprising a total of 1,152 participants (704 from the SB11 trial and 448 from the SB15 trial) with nAMD. Screening duration was assessed in relation to changes in best-corrected visual acuity (BCVA) and central subfield thickness (CST) at weeks 8 and 48. Multiple linear and logistic regression analyses, adjusted for age and baseline BCVA/CST, showed no significant associations between screening duration and either visual or anatomical outcomes at both time points. Linear regression coefficients for screening duration were not statistically significant for BCVA or CST at week 8 (BCVA: B = - 0.058, P = 0.242; CST: B = - 0.050, P = 0.908) or at week 48 (BCVA: B = - 0.015, P = 0.843; CST: B = 0.036, P = 0.930). These findings suggest that a screening period of up to 21 days does not adversely affect treatment efficacy in clinical trial settings and support the clinical feasibility of short pre-treatment delays.},
}

@article {pmid41918827,
year = {2026},
author = {Stewart, C and Bhangu, JS and Swarnkar, PK and Rifat, M and Khalid, S and Al-Janabi, A and Awad, MH and Williams, GS},
title = {Real-World Outcomes of Switching to Faricimab in Treatment-Experienced and Resistant Neovascular Age-Related Macular Degeneration: A Single-Centre Retrospective Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {591029},
pmid = {41918827},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate anatomical, functional, and treatment burden outcomes of Faricimab in neovascular age-related macular degeneration (nAMD) patients with persistent disease activity despite prior anti-VEGF therapy.

PATIENTS AND METHODS: Single-centre retrospective study of 67 eyes switched to Faricimab (November 2022-December 2024). This cohort was unable to be extended beyond 4-6-week intervals on existing anti-VEGF therapy. All patients received three monthly loading doses followed by treat-and-extend regimen. Primary outcomes: central macular thickness (CMT), best-corrected visual acuity (BCVA), macular dryness over eight injections, and treatment interval extension.

RESULTS: The cohort had received mean 33 (range 10-78) prior anti-VEGF. Baseline mean BCVA was 0.42 logMAR (SD ± 0.28) and mean CMT was 244.5 μm (SD ± 62.2). Statistically significant CMT reduction occurred by injection 8 (-16.9 μm, p=0.0084). Complete macular dryness peaked by the time of third injection (43.3%) then declined to 32.8% at injection 8 (p=0.0089). Visual acuity remained unchanged (p=0.6043) with no correlation to CMT change (p=0.172). Treatment interval extension was achieved in 46.3% of patients (p=0.002). Dryness at injection 3 after switching to Faricimab did not predict treatment extension (p=0.217). Two patients (0.36% of total injections, 2/548) developed sterile intraocular inflammation requiring discontinuation.

CONCLUSION: Faricimab switching achieves statistically significant but modest anatomical improvement in heavily pretreated nAMD with meaningful treatment burden reduction in 46.3% of eyes. Our analysis revealed treatment burden did not indicate the potential for treatment interval extension.},
}

@article {pmid41918832,
year = {2026},
author = {Wang, R and Durrani, AK},
title = {Severe Pancytopenia Secondary to Zinc Toxicity from Age-Related Eye Disease Study Vitamin Supplementation.},
journal = {Journal of vitreoretinal diseases},
volume = {},
number = {},
pages = {24741264261436350},
pmid = {41918832},
issn = {2474-1272},
abstract = {Purpose: To report a case of zinc-induced hypocupremia associated with Age-Related Eye Disease Study 2 supplementation presenting with pancytopenia. Methods: A single case was retrospectively reviewed. Results: An 86-year-old woman taking Age-Related Eye Disease Study 2 supplementation presented to a hematology-oncology clinic with severe fatigue and pancytopenia. Laboratory evaluation demonstrated elevated zinc levels and low copper levels consistent with zinc-induced hypocupremia. Age-Related Eye Disease Study supplementation was discontinued, and the patient was started on copper supplementation. At the 4-month follow-up, the patient demonstrated near normalization of hematologic parameters and resolution of symptoms. Conclusions: Zinc-induced hypocupremia is a rare but potentially fatal complication of Age-Related Eye Disease Study 2 supplementation and may present with pancytopenia. Clinicians should consider this diagnosis in patients taking zinc-containing supplements who present with unexplained cytopenias.},
}

@article {pmid41919172,
year = {2026},
author = {Ambrosio, L and Cammalleri, M and Panariello, S and Califano, G and Scala, A and Improta, G and Pisani, A and Rejdak, R and Ostrowski, I and Filippi, L and Bagnoli, P and Dal Monte, M and Toro, MD},
title = {Mirabegron in patients with age-related macular degeneration treated for overactive bladder: a study protocol for a prospective observational non-randomized trial.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1761473},
pmid = {41919172},
issn = {2296-858X},
abstract = {UNLABELLED: Although anti-vascular endothelial growth factor drugs have revolutionized the treatment of neovascular age-related macular degeneration (wet AMD), preventing eyes from converting from dry to wet AMD provides better long-term prognosis for sight and overall health. Mirabegron, an agonist at beta 3 adrenoceptors (β3-ARs), is licensed for the treatment of overactive bladder (OAB), but has potential effects on angiogenic proliferation in the retina, and therefore may reduce risk of conversion from dry to wet AMD. Both OAB and AMD are more common in older adults and share risk factors suggesting a potential link between these two conditions, thus highlighting the need for common therapy for the two diseases. Mirabegron use in AMD patients is supported by its rather safe profile at the eye level as macular and choriocapillary parameters do not seem to be affected in OAB patients. The purpose of this study will be to investigate the effects of mirabegron in patients concomitantly affected by OAB and dry AMD to evaluate its impact on slowing down AMD progression from the dry to the neovascular form.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT07305298, identifier NCT07305298.},
}

@article {pmid41922489,
year = {2026},
author = {Morsy, MS and Dutta, NA and Eldessouky, EI and Kabil, MM and El-Koumy, HAEA and Mehta, NN and Ali, AL and Jena, S and Zhang, H and Bartsch, DU and Cheng, L and An, C and Nguyen, T and Freeman, WR},
title = {Artificial intelligence based assessment of treatment response in wet age related macular degeneration using paired OCT angiography.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-42999-7},
pmid = {41922489},
issn = {2045-2322},
support = {P30EY022589//UCSD Vision Research Center Core Grant/ ; R01EY033847,//NIH grant/ ; },
}

@article {pmid41913248,
year = {2026},
author = {Hanhart, J and Celi, LA and Blumenthal, EZ and Almog, R and Behar, J},
title = {Artificial intelligence in retinal care: transforming the doctor-patient partnership.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00837-y},
pmid = {41913248},
issn = {2056-9920},
abstract = {BACKGROUND: The integration of artificial intelligence into retinal practice represents more than a technological advancement; it constitutes an anthropological shift fundamentally redefining the centuries-old therapeutic partnership between physician and patient.

OBJECTIVE: To examine how artificial intelligence integration into retinal care transforms the therapeutic partnership, revealing what this transformation illuminates about the nature of medical knowledge itself and identifying frameworks for conscious implementation.

METHODS: We conducted a structured narrative review examining AI-based diagnosis and monitoring of diabetic retinopathy and age-related macular degeneration (2018-2025), synthesizing clinical deployment evidence with qualitative implementation studies, adopting an anthropological interpretive stance to examine technology as a mediator of human relationships.

RESULTS: FDA-approved AI systems demonstrate robust diagnostic performance for diabetic retinopathy and age-related macular degeneration. AI integration shifts encounters from examination-based to screen-mediated, clinical reasoning from individual to algorithm-guided, and physicians from diagnosticians to interpreters. Three insights emerge. First, AI reveals that medical practice always combined mechanistic reasoning with pattern recognition, now separated algorithmically. Second, accountability operates asymmetrically: while all stakeholders derive benefits from algorithmic integration, authority over system selection and deployment remains concentrated among vendors and institutions rather than distributed to frontline clinicians or patients. Third, impact diverges along existing stratification: transformation may create access for excluded populations while potentially eroding relationships for those who had comprehensive care, raising fundamental questions about equitable distribution.

CONCLUSIONS: The AI transformation of retinal care offers a revealing mirror of medicine's algorithmic future. Success demands epistemological rigor, robust evaluation competencies and establishing frameworks for shared accountability among the various stakeholders. Our framework maps six fundamental dimensions where synthesis supersedes substitution: expanding algorithmic capabilities while preserving healing relationships, creating access while maintaining continuity. Medicine can embrace algorithmic intelligence while preserving its humanistic core through conscious choices about epistemology, equity, and the character of practice we create.},
}

@article {pmid41914966,
year = {2026},
author = {Trinh, M and Nguyen, J and Lee, M and Wang, J and Tee, YG and Nivison-Smith, L},
title = {Eccentricity-Dependent Reflectivity Rates-of-Change Across the Retina in Intermediate Age-Related Macular Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {3},
pages = {62},
doi = {10.1167/iovs.67.3.62},
pmid = {41914966},
issn = {1552-5783},
mesh = {Humans ; Tomography, Optical Coherence/methods ; Retrospective Studies ; Female ; Male ; Aged ; *Macular Degeneration/diagnosis ; *Retinal Ganglion Cells/pathology ; Bruch Membrane/pathology ; *Retinal Pigment Epithelium/pathology ; Aged, 80 and over ; Nerve Fibers/pathology ; Middle Aged ; *Retina/pathology ; Longitudinal Studies ; Disease Progression ; Visual Acuity ; Follow-Up Studies ; },
abstract = {PURPOSE: The purpose of this study was to characterize reflectivity rates-of-change and eccentricity patterns across all retinal layers and bands in intermediate age-related macular degeneration (iAMD), using topographical optical coherence tomography (OCT) analysis.

METHODS: This retrospective, longitudinal study included 58 consecutive individuals with iAMD and no progression to late AMD. Linear reflectivity was derived from manually segmented OCT macular cubes (25 × 25 degrees) across 60 × 60 grids and normalized to vitreous reflectivity, for each reflective retinal layer from the retinal nerve fiber layer (RNFL) to Bruch's membrane (BM). This included the outer retinal bands, that is, the external limiting membrane (ELM), ellipsoid zone (EZ), and retinal pigment epithelium (RPE), and the drusen layer (RPE-BM). Grids below large blood vessels, the optic nerve head, and above drusen were excluded. Reflectivity rates-of-change (median, interquartile range [IQR], %/year) and eccentricity patterns were evaluated, then compared with colocalized thickness using regression coefficient ratios.

RESULTS: RNFL and ganglion cell layer reflectivity decreased up to -10.2%/year, with para-foveal troughs at 1.5 to 1.6 mm eccentricity. Inner plexiform and outer plexiform layers showed more uniform decreases without eccentricity dependence. In the outer retina, EZ band reflectivity decreased with a parafoveal trough of -11.1%/year at 1.4 mm, whereas ELM band, RPE band, and drusen layer changes were smaller and spatially uniform (within ±3%/year). Reflectivity rates-of-change were up to 15 × [IQR = 1.47-28.53] faster than thickness (P < 0.05), although relationships (R2) were weak.

CONCLUSIONS: In iAMD, reflectivity changes across all retinal layers, most prominently para-/centrally, and show minimal colocalization with thickness. Faster rates-of-change and distinct spatial profiles support reflectivity as a sensitive biomarker for early disease change over time.},
}

Humans
Tomography, Optical Coherence/methods
Retrospective Studies
Female
Male
Aged
*Macular Degeneration/diagnosis
*Retinal Ganglion Cells/pathology
Bruch Membrane/pathology
*Retinal Pigment Epithelium/pathology
Aged, 80 and over
Nerve Fibers/pathology
Middle Aged
*Retina/pathology
Longitudinal Studies
Disease Progression
Visual Acuity
Follow-Up Studies

@article {pmid41915734,
year = {2026},
author = {Bordon, AF and Kaiser, PK and Wolf, A and Cen, L and Heyn, J and Urosevic, D and Dodeller, F and Allmannsberger, L and Silva, R},
title = {Efficacy and Safety of the Proposed Biosimilar Aflibercept, SDZ-AFL, in Patients With Neovascular Age-Related Macular Degeneration: 52-Week Results From the Phase 3 Mylight Study: Erratum.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004832},
pmid = {41915734},
issn = {1539-2864},
}

@article {pmid41916277,
year = {2026},
author = {Spirig, SE and Herrero-Navarro, Á and Utz, L and Arteaga-Moreta, VJ and Raics, Z and Posada-Céspedes, S and Chreng, S and Galuba, O and Galuba, I and Claerr, I and Renner, S and Boldogkoi, M and Moreno-Juan, V and Kleindienst, PT and Volak, A and Imbach, J and Malysheva, S and Siwicki, RA and Hahaut, V and Hou, Y and Rodrigues, TM and Picelli, S and Cattaneo, M and Jüttner, J and Cowan, CS and Duckely, M and Baeschlin, DK and Renner, M and Unterreiner, V and Roska, B},
title = {Cell-type-focused compound screen in human organoids reveals CK1 inhibition protects cone photoreceptors from death.},
journal = {Neuron},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.neuron.2026.02.024},
pmid = {41916277},
issn = {1097-4199},
abstract = {Human organoids that mirror their corresponding organs in cell-type diversity present an opportunity to perform large-scale screens for compounds that protect disease-affected or damaged healthy cell types. Here, we generated 20,000 human retinal organoids with green fluorescent protein (GFP)-labeled cone photoreceptors. Since degeneration of cones is a leading cause of blindness, we induced cone death and screened 2,707 compounds with known targets for those that saved cones or those that further damaged cones. We identified inhibitors of casein kinase 1 (CK1) that protected cones, heat shock protein 90 (HSP90) inhibitors that saved cones in the short term but damaged them in the longer term, and broad histone deacetylase (HDAC) inhibition by many compounds that significantly damaged cones. Finally, we confirmed the protective effects of identified compounds in a mouse model of photoreceptor degeneration. This work provides a database for cone-damaging compounds and describes compounds and targets that can be starting points to develop neuroprotection for cones in diseases such as macular degeneration.},
}

@article {pmid41916527,
year = {2026},
author = {Chen, Y and Zhang, Z and Wu, J and Wang, Y and Lin, S},
title = {MiR-335-5p as a potential biomarker of wet age-related macular degeneration.},
journal = {Clinical & experimental optometry},
volume = {},
number = {},
pages = {1-11},
doi = {10.1080/08164622.2026.2639834},
pmid = {41916527},
issn = {1444-0938},
abstract = {CLINICAL RELEVANCE: Early diagnosis and intervention are of vital importance in delaying the irreversible vision loss caused by wet age-related macular degeneration (wAMD).

BACKGROUND: wAMD can lead to blindness in severe cases. At present, the pathogenesis of wAMD is still unclear, so a new biomarker is needed to study wAMD.

METHODS: A total of 190 subjects were included in this study, including the control group (n = 90) and the wAMD group (n = 100). The expression of miR-335-5p and the diagnostic value of miR-335-5p in wAMD were analysed. ARPE-19 cells treated with 300 µM t-BHP for 24 h or 600 µM H2O2 for 24 h were selected as oxidative damage models. MiR-335-5p mimic and miR-335-5p inhibitor were transfected into oxidative damage models to up-regulate and down-regulate miR-335-5p, and then proliferation and apoptosis were measured. Targetscan was used to forecast the target of miR-335-5p and gain VEGFA, which was confirmed by the dual-luciferase reporter system. MiR-335-5p and VEGFA were overexpressed in oxidative damage models to detect the role of both in wAMD.

RESULTS: MiR-335-5p was reduced and may have high diagnostic value in wAMD. MiR-335-5p was a risk factor for wAMD. In the oxidative damage models, overexpressed miR-335-5p increased the cell viability and decreased the apoptosis, while the inhibition of miR-335-5p was reversed. VEGFA was the target of miR-335-5p and was negatively regulated by miR-335-5p in the oxidative damage models. VEGFA and miR-335-5p were negatively correlated in wAMD.

CONCLUSION: MiR-335-5p may have a high diagnostic value in wAMD, suggesting that miR-335-5p might be a biomarker of wAMD. VEGFA was the target of miR-335-5p, and the two were negative correlation in wAMD. MiR-335-5p regulates VEGFA secretion in RPE cells, thereby indirectly participating in the core pathological process of wAMD.},
}

@article {pmid41907382,
year = {2026},
author = {Hwang, S and Kang, SW and Kim, SJ and Park, KH and Oh, J and Jo, YJ and Byeon, SH and Kim, JH and Son, KY and Choi, J and Sagong, M and Kim, K and Yu, SY and Hwang, DD and Park, YH and Lee, H and Choi, EJ and Lee, J and , },
title = {Design and Baseline Characteristics of the Korean Age-Related Maculopathy Study (KARMS): A Nationwide Multicenter Prospective Observational Study.},
journal = {Ophthalmology science},
volume = {6},
number = {4},
pages = {101121},
pmid = {41907382},
issn = {2666-9145},
abstract = {PURPOSE: To describe the design and baseline characteristics of the Korean Age-Related Maculopathy Study, a nationwide prospective cohort investigating age-related macular degeneration (AMD) in Koreans.

DESIGN: A 5-year prospective observational study conducted across 33 tertiary hospitals and ophthalmology clinics in Korea.

PARTICIPANTS: A total of 1159 Korean participants diagnosed with nonexudative or exudative AMD.

METHODS: Participants aged 50 to 80 years were assigned to the A Study for Intermediate AMD Natural Outcome (ASIANO) arm (nonexudative) or Korean Exudative AMD Treatment Study (KEATS) arm (newly diagnosed exudative AMD). A Study for Intermediate AMD Natural Outcome arm 1 included bilateral intermediate AMD with classic drusen (soft, reticular pseudodrusen, cuticular, or calcified drusen) without advanced AMD. A Study for Intermediate AMD Natural Outcome arm 2 included pachychoroid spectrum disease with unilateral or bilateral findings such as pachydrusen with retinal pigment epithelium undulation, focal attenuation of inner choroidal vessel, and dilated outer choroidal vessels or pigmentary abnormalities corresponding retinal pigment epithelium elevation or disruption in OCT, without significant classic drusen. The KEATS arm comprised active exudative AMD, including typical exudative macular neovascularization, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation. All underwent standardized multimodal imaging at baseline and are followed annually.

MAIN OUTCOME MEASURES: Baseline demographic, behavioral, and ocular characteristics across drusen-driven, pachychoroid-driven, and exudative AMD phenotypes.

RESULTS: Of the 1409 individuals screened, 1159 were enrolled (ASIANO 1: 551; ASIANO 2: 317; KEATS: 291). A Study for Intermediate AMD Natural Outcome arm 1 participants were older, predominantly female, and universally bilateral; arm 2 participants were younger, more often male, and frequently unilateral. Korean Exudative AMD Treatment Study showed a high proportion of patients with polypodal choroidal vasculopathy (39.5%, patient-based) and male predominance. Behavioral profiles also differed: the KEATS arm had lower eye-supplement use, higher smoking exposure, and less frequent sunglasses/sun-visor use. Exploratory follow-up analyses suggested differing rates of exudative conversion between ASIANO arm 1 and arm 2.

CONCLUSIONS: Korean Age-Related Maculopathy Study is the first large-scale, nationally representative prospective cohort in Koreans, distinguishing drusen-driven and pachychoroid-driven maculopathy phenotypes and detailing exudative subtypes. These baseline data provide a foundation for future phenotype-specific progression analyses and management strategies in Asian populations.

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

@article {pmid41910764,
year = {2026},
author = {Savastano, MC and Fossataro, C and Hu, L and Mottola, F and D'Onofrio, NC and Cestrone, V and Giannuzzi, F and Rizzo, S},
title = {Non neovascular Age - related macular degeneration - Review on clinical and imaging advances.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41910764},
issn = {1435-702X},
}

@article {pmid41912546,
year = {2026},
author = {Mani, P and Ramachandran, N and Sowmya, V and Ravi, V and Ramesh, PV and Alahmadi, TJ},
title = {Multi-scale adaptive fusion network for retinal layer and fluid segmentation in optical coherence tomography B-scans.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44006-5},
pmid = {41912546},
issn = {2045-2322},
abstract = {Major treats to visual health includes diabetic macular edema (DME), age-related macular degeneration (AMD) and retinal vein occlusion (RVO), which require prompt and correct interpretation for effective treatment. Optical coherence tomography (OCT) is an imaging modality, providing intense cross-sectional views of the retina to aid in diagnosis. Diagnosis and localization of retinal diseases were complicated by the structure of retinal fluids. In order to cope with these challenges, a deep learning architecture, the Adaptive Multi-Domain Fusion Network (AMDF-Net), is initiated to improve the detection of retinal diseases. AMDF-Net assimilates state of the art modules like Hybrid Spectral-Spatial Transformer (HSST) to gain insight about global and local features effectively. Moreover, the Dynamic Attention Fusion (DAF) module enhances the work of the network by specifying the features unique to retinal fluids, and Disease-Inclusive Segmentation (DIS) module makes it easier to accurately diagnose primary fluids. Extensive analyses of publicly available and real-time data reveal that AMDF-Net shows notable results with Dice coefficient of 98. 87% and classification accuracy of 98. 12%. These remarks highlight the potential of AMDF-Net to elevate automated retinal disease analysis and provide valuable assistance in the development of decisions focused on treatment.},
}

@article {pmid41904432,
year = {2026},
author = {Bulut, M and Reyhan, AH},
title = {A comparison of GPT-4V's capability in optical coherence tomography images of age-related macular degeneration with expert assessments.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04777-x},
pmid = {41904432},
issn = {1471-2415},
}

@article {pmid41896965,
year = {2026},
author = {Kochnev Goldstein, A and Park, J and Zhou, Y and Jensen, N and Palanker, D},
title = {Simulation of prosthetic vision with the PRIMA system and enhancement of face representation.},
journal = {Journal of neuroengineering and rehabilitation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12984-026-01958-z},
pmid = {41896965},
issn = {1743-0003},
support = {R01-EY-035227/NH/NIH HHS/United States ; W81XWH-22-1-0933//Department of Defense/ ; FA9550-19-1-0402//Air Force Office of Scientific Research/ ; },
abstract = {OBJECTIVE: Patients implanted with the PRIMA photovoltaic subretinal prosthesis in geographic atrophy report form vision with the average acuity matching the 100 μm pixel size. Although this remarkable outcome enables them to read and write, they report difficulty with perceiving faces. Despite the pixelated stimulation, patients report seeing smooth patterns rather than dots. This paper provides a novel, non-pixelated algorithm for simulating prosthetic vision the way it is experienced by PRIMA patients, compares the algorithm's predictions to clinical perceptual outcomes, and offers computer vision and machine learning (ML) methods to improve face representation.

APPROACH: Our simulation algorithm (ProViSim) integrates a grayscale filter, spatial resolution filter, and contrast filter. This accounts for the limited sampling density of the retinal implant (pixel pitch), as well as the reduced contrast sensitivity of prosthetic vision. Patterns of Landolt C and faces created using this simulator are compared to reports from actual PRIMA users. To recover the facial features lost in prosthetic vision due to limited resolution or contrast, we apply an ML facial landmarking model, as well as contrast-adjusting tone curves to the image prior to its projection onto the photovoltaic retinal implant.

MAIN RESULTS: Prosthetic vision simulated using the above algorithm matches the maximum letter acuity observed in clinical studies, as well as the patients' subjective descriptions of perceived facial features. Applying the inversed contrast filter to the image prior to its projection onto the implant and accentuating the facial features using an ML facial landmarking model helps preserve the contrast in prosthetic vision, improves emotion recognition and reduces the response time.

SIGNIFICANCE: Spatial and contrast constraints of prosthetic vision limit resolvable features and degrade natural images. ML based methods and contrast adjustments prior to image projection onto the implant mitigate some limitations and improve face representation. Even though higher spatial resolution can be expected with implants having smaller pixels, contrast enhancement still remains essential for face recognition.},
}

@article {pmid41897380,
year = {2026},
author = {Kaštelan, S and Antunica, AG and Konjevoda, S and Tomić, Z and Sarić, A and Kulaš, M and Kulaš, L and Begović, EK and Čanović, S and Kovačević, P and Ivanković, M},
title = {Mitochondrial ROS in Retinal Neurodegeneration: Thresholds, Quality Control Failure, and Precision Therapeutic Windows.},
journal = {Biomolecules},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/biom16030445},
pmid = {41897380},
issn = {2218-273X},
mesh = {Humans ; *Reactive Oxygen Species/metabolism ; *Mitochondria/metabolism/pathology ; Animals ; Oxidative Stress ; Oxidation-Reduction ; *Neurodegenerative Diseases/metabolism/pathology ; *Retina/metabolism/pathology ; },
abstract = {Mitochondrial reactive oxygen species (mtROS) play a dual role in retinal physiology, acting as essential redox signalling mediators under homeostatic conditions but driving oxidative damage and neurodegeneration once regulatory thresholds are exceeded. Owing to the exceptionally high energetic demands of retinal neurons and supporting cells, even subtle perturbations in mitochondrial redox balance can precipitate progressive retinal dysfunction. Increasing evidence indicates that retinal neurodegenerative diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and inherited optic neuropathies, are characterised not by uniform oxidative stress, but by disease- and stage-specific mtROS signatures shaped by mitochondrial quality control capacity. This review synthesises current insights into the sources, regulation, and signalling functions of mtROS in the retina, with particular emphasis on threshold-dependent redox transitions, reverse electron transport, and the progressive failure of mitochondrial quality control mechanisms, including mitophagy, mitochondrial dynamics, and redox-responsive transcriptional networks. The limitations of non-selective antioxidant strategies are critically examined, highlighting why indiscriminate ROS suppression has yielded limited clinical benefit. In contrast, emerging therapeutic approaches aimed at recalibrating mitochondrial redox homeostasis, rather than abolishing physiological signalling, are discussed in the context of disease stage, metabolic state, and mitochondrial competence. By integrating redox biology with mitochondrial quality control and precision medicine concepts, this review proposes a unifying framework in which retinal neurodegeneration is governed by regulated mtROS signalling and the progressive exhaustion of mitochondrial resilience. This model defines critical therapeutic windows for mitochondria-targeted intervention and provides a framework for biomarker-guided patient stratification.},
}

Humans
*Reactive Oxygen Species/metabolism
*Mitochondria/metabolism/pathology
Animals
Oxidative Stress
Oxidation-Reduction
*Neurodegenerative Diseases/metabolism/pathology
*Retina/metabolism/pathology

@article {pmid41897428,
year = {2026},
author = {Roberson, JK and Bauer, AN and Lopez-Ramirez, A and Jenness, DB and Cruz Zayas, S and Cooke Bailey, JN and Woodlief, TL},
title = {Environmental Exposures and Oxidative Stress in Retinal and Optic Nerve Diseases: Mechanisms, Consequences, and Therapeutic Opportunities.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {3},
pages = {},
doi = {10.3390/antiox15030281},
pmid = {41897428},
issn = {2076-3921},
support = {Institutional Startup Funds//East Carolina University Brody School of Medicine/ ; },
abstract = {Oxidative stress is a key contributing and convergent pathogenic mechanism linked to retinal and optic nerve diseases including age-related macular degeneration, diabetic retinopathy, and glaucoma. The retina is highly susceptible to redox imbalance due to intense mitochondrial activity, oxygen consumption, and light exposure. While endogenous drivers are well recognized, the contribution of environmental exposure to retinal oxidative injury remains incompletely defined. This review uniquely integrates emerging environmental contaminants with canonical oxidative stress pathways. We examine how cigarette smoke, ultraviolet radiation, heavy metals, microplastics, and per- and polyfluoroalkyl substances (PFASs) promote oxidative injury through mitochondrial dysfunction, inflammatory signaling, impaired antioxidant responses, and ferroptotic pathways. We also highlight therapeutic strategies targeting oxidative pathways and emphasize the importance of exposure-informed retinal and optic nerve disease research.},
}

@article {pmid41898716,
year = {2026},
author = {Calbay, O and Hsieh, CL and Lu, C and Ghosh, S and Vijaykumar, V and Watts, I and Sweigard, H and Gandhi, J and den Hollander, AI},
title = {Mapping the Hypoxic Fitness Landscape of Retinal Pigment Epithelial Cells.},
journal = {International journal of molecular sciences},
volume = {27},
number = {6},
pages = {},
doi = {10.3390/ijms27062857},
pmid = {41898716},
issn = {1422-0067},
mesh = {*Retinal Pigment Epithelium/metabolism/cytology ; Humans ; Cell Hypoxia/genetics ; Gene Expression Profiling ; Cell Line ; Transcriptome ; Macular Degeneration/genetics/metabolism/pathology ; CRISPR-Cas Systems ; *Epithelial Cells/metabolism ; Mitochondria/metabolism ; *Hypoxia/genetics ; Oxygen/metabolism ; },
abstract = {Chronic hypoxia is a hallmark of aging and retinal diseases such as age-related macular degeneration (AMD), yet the molecular mechanisms that enable retinal pigment epithelium (RPE) cells to survive under sustained low-oxygen conditions remain poorly understood. To address this, we conducted transcriptomic profiling and a genome-wide CRISPR-Cas9 loss-of-function screen in ARPE-19 cells exposed to chronic hypoxia (1% and 5% O2), mimicking the retinal disease environment. The CRISPR screen identified genes whose loss compromises RPE viability or fitness under hypoxia, while transcriptomic profiling revealed oxygen-dependent shifts in key functional modules. These findings converged on pathways related to mitochondrial function, extracellular matrix remodeling, vascular signaling, and cell cycle regulation, identifying unique functional nodes specific to RPE cells. These core processes are also implicated in retinal diseases, such as AMD. Together, these complementary approaches provide an integrated view of the molecular networks driving RPE adaptation to hypoxic stress and highlight novel gene candidates that may serve as therapeutic targets in retinal disease.},
}

*Retinal Pigment Epithelium/metabolism/cytology
Humans
Cell Hypoxia/genetics
Gene Expression Profiling
Cell Line
Transcriptome
Macular Degeneration/genetics/metabolism/pathology
CRISPR-Cas Systems
*Epithelial Cells/metabolism
Mitochondria/metabolism
*Hypoxia/genetics
Oxygen/metabolism

@article {pmid41901080,
year = {2026},
author = {Baek, HI and Kim, I and Bae, J and Kwon, JE and Kang, SC},
title = {Effects of Long-Term Supplementation with Centella asiatica (L.) Urb. Extract (CA-HE50) on Macular Pigment Optical Density: A Randomized, Double-Blind, Placebo-Controlled Trial.},
journal = {Nutrients},
volume = {18},
number = {6},
pages = {},
doi = {10.3390/nu18060905},
pmid = {41901080},
issn = {2072-6643},
support = {117050-3//Ministry of Agriculture, Food and Rural Affairs/ ; },
mesh = {Humans ; Double-Blind Method ; Female ; Middle Aged ; Male ; *Plant Extracts/administration & dosage/pharmacology ; *Dietary Supplements ; *Centella/chemistry ; Aged ; *Triterpenes/administration & dosage/pharmacology ; *Macular Pigment/metabolism ; Antioxidants ; *Macula Lutea/drug effects/metabolism ; },
abstract = {Background/Objectives: Macular pigment optical density (MPOD) is a nutrition-responsive biomarker that indicates the antioxidant status of the macula. This study aimed to evaluate the effects of long-term supplementation with a standardized Centella asiatica (L.) Urb. extract (CA-HE50) on MPOD in a randomized, double-blind, placebo-controlled clinical trial. Methods: Eighty men and women aged 45-65 years, with baseline MPOD values between 0.2 and 0.4, were randomly assigned to receive either CA-HE50 (300 mg/day, n = 40) or a placebo (n = 40) for 6 months. Efficacy was assessed by measuring MPOD at baseline and on Days 60, 120, and 180. The primary efficacy endpoint was the change in MPOD from baseline to Day 180. Safety was evaluated through monitoring adverse events, vital signs, and clinical laboratory tests. Results: By Day 180, supplementation with CA-HE50 resulted in a statistically significant increase in MPOD compared to the placebo in the right eye, left eye, and the average of both eyes (all p < 0.001). Significant between-group differences were also observed at Day 120, indicating a time-dependent improvement in MPOD. Additionally, the proportion of responders was significantly higher in the CA-HE50 group compared to the placebo group (p < 0.001). CA-HE50 was well tolerated, with no serious adverse events or clinically relevant safety concerns identified during the intervention period. Conclusions: Long-term supplementation with C. asiatica extract significantly improved MPOD, supporting its potential role in enhancing macular nutritional status. These findings suggest that CA-HE50 may serve as a beneficial dietary intervention for maintaining macular health.},
}

Humans
Double-Blind Method
Female
Middle Aged
Male
*Plant Extracts/administration & dosage/pharmacology
*Dietary Supplements
*Centella/chemistry
Aged
*Triterpenes/administration & dosage/pharmacology
*Macular Pigment/metabolism
Antioxidants
*Macula Lutea/drug effects/metabolism

@article {pmid41888298,
year = {2026},
author = {Krasniakova, M and Pansell, T and Gustafsson, J},
title = {Impact of individualized colored spectacle filters on photophobia and visual comfort in central visual field defect patients: a one-year study.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-45302-w},
pmid = {41888298},
issn = {2045-2322},
abstract = {Visual comfort is a critical yet often overlooked aspect in managing patients with central visual field defects and photophobia. This study investigates the long-term effects of individualized colored spectacle filters on visual comfort and function in patients with Age-related Macular Degeneration and Leber Hereditary Optic Neuropathy. Patients were fitted with individualized precision tint spectacles tailored to improve vision comfort for one year. The study involved a comprehensive evaluation of visual acuity, contrast sensitivity, and photophobia symptoms alongside qualitative feedback from patient interviews. Results indicate significant improvements in subjective visual comfort and function, with a notable reduction in photophobia symptoms among patients with Leber Hereditary Optic Neuropathy. Colored filters, particularly those in the blue-green spectrum, were preferred by most patients and had a positive impact on comfort. Statistical analysis revealed trends in color preferences and subjective enhancements in visual function, underscoring the potential benefits of comfort-tint filters and the importance of personalized treatment approaches. The findings suggest that individualized colored spectacle filters can be valuable in enhancing visual comfort and function for patients with central visual field defects. This study shows the importance of integrating visual comfort considerations into clinical practice for a comprehensive approach to patient care.},
}

@article {pmid41888985,
year = {2026},
author = {Helland-Hansen, BA and Sverstad, A and Petrovski, G and Larsen, SE},
title = {Eye-tracking-derived foveal biomarkers and functional alterations in dry AMD: findings from a controlled clinical study.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00838-x},
pmid = {41888985},
issn = {2056-9920},
support = {333925//Norges Forskningsråd/ ; 333925//Norges Forskningsråd/ ; 333925//Norges Forskningsråd/ ; 333925//Norges Forskningsråd/ ; },
}

@article {pmid41889981,
year = {2026},
author = {Meng, R and Kenney, RC and Pan, M and Gupta, AK and Modi, YS and Chauhan, P and Curcio, CA and Srinivasan, VJ},
title = {Visible Light Optical Coherence Tomography Reveals Aging at the Retinal Pigment Epithelium-Bruch's Membrane Interface.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.18.712487},
pmid = {41889981},
issn = {2692-8205},
abstract = {UNLABELLED: Landmark histological studies have shown that as the retina ages, lipids and other debris accumulate within Bruch's membrane (BM) and in spaces introduced between BM and the retinal pigment epithelium (RPE). These deposits grow with age, increasing the risk of age-related macular degeneration (AMD), the leading cause of irreversible vision loss for older adults globally. Current in vivo imaging lacks specificity to study BM and the important spaces at the RPE/BM interface in living human eyes, while histological techniques suffer from processing artifacts that distort photoreceptors. Here we employ visible light Optical Coherence Tomography (OCT), with 1 micrometer depth resolution, to quantitatively analyze these tissues in living eyes. We identify age-related changes in a human cohort without retinal pathology: thickening and loss of contrast of the hyper-reflective BM band, and thickening of the RPE together with the sub-RPE basal laminar space (RPE+sBL). Both forms of thickening were locally coupled depending on eccentricity, suggesting related biosynthetic mechanisms. A thicker BM and RPE+sBL were locally associated with anomalies in the overlying photoreceptors. Thus, sub-clinical changes in aging eyes detected by visible light OCT resemble early versions of deposits found in AMD. Visible light OCT depicts the relationship between RPE+sBL, BM, and photoreceptors in aging, holding promise to precisely and non-invasively grade ocular phenotypes ranging from normal aging to early AMD.

SIGNIFICANCE STATEMENT: As humans age, lipids and other debris deposit in Bruch's membrane (BM) of the human eye (1) and spaces introduced between the retinal pigment epithelium (RPE) and BM. These deposition processes are linked to the eventual development of age-related macular degeneration (AMD), the leading blinding disease amongst older adults. Here we investigate these deposits with visible light OCT imaging in living human subjects without overt retinal pathology. Whereas early RPE/BM deposits were previously assessed only in donor eyes postmortem via preparations that distort photoreceptors, our results shed light on these AMD precursors and overlying photoreceptor changes in living human eyes.},
}

@article {pmid41890681,
year = {2026},
author = {Agius, D and Mamo, J and Calleja, N and Cassar, D and Marku, X and Nappa, MC and Zammit, M and Pace, ME and Carbonaro, F},
title = {Prevalence of Refractive Errors, Myopic Macular Degeneration, and Associated Risk Factors in a Maltese Population-Based Study.},
journal = {Clinical optometry},
volume = {18},
number = {},
pages = {561426},
pmid = {41890681},
issn = {1179-2752},
abstract = {PURPOSE: To estimate the prevalence of refractive error and myopic macular degeneration in a nationally representative sample of older adults from Malta, evaluate associations with established risk factors.

PATIENTS AND METHODS: This population-based cross-sectional study included 1,794 participants aged 50-80 years from Malta, recruited as part of The Malta Eye Study (response rate 44.8%). Demographic, medical, behavioral, and ocular data were collected using structured questionnaires. Standardized ophthalmic examinations were performed, including autorefraction and retinal imaging with optical coherence tomography. Refractive error was classified by spherical equivalent as myopia (< -0.50 D) and hyperopia (> +0.50 D), while astigmatism was defined as ≤ -0.75 D. Myopic macular degeneration was graded using the meta-analysis for pathologic myopia classification. Associations were assessed using multivariable logistic regression.

RESULTS: Among right phakic, surgically untouched eyes, the prevalence of emmetropia, myopia, and hyperopia was 20.0% (95% CI 18.0-22.1%), 25.1% (95% CI 23.0-27.4%), and 54.8% (95% CI 52.3-57.3%), respectively. Vector-derived average astigmatism prevalence in both eyes was 44.3% (95% CI 41.6-46.9%), with against-the-rule astigmatism being the most common pattern. Effective refractive error coverage exceeded 90% for both distance and near vision. The prevalence of any myopic degeneration in either eye was 2.6% (95% CI 1.9-3.4%). Myopia prevalence among individuals aged 50-59 years was lower than that reported in other European populations, and use of long-acting anti-muscarinic agents was associated with myopic degeneration (OR 25.70, 95% CI 1.55-426.04, p=0.023).

CONCLUSION: This study reports refractive error and myopic macular degeneration prevalence broadly comparable to other European settings. Lower myopia prevalence among individuals aged 50-59 years may reflect complex gene-environment-behavior interactions. Further investigation of these interactions, as well as the potential impact of long-acting anti-muscarinic agents on myopic macular degeneration, is warranted, particularly in light of the wide confidence interval.},
}

@article {pmid41891014,
year = {2026},
author = {Yeh, TC and Velez, G and Prasad, A and Lee, SH and Rasmussen, DK and Kumar, A and Chadha, M and Dabaja, MZ and Singh, AM and Sanislo, S and Smith, S and Mryuthyunjaya, P and Montague, A and Bassuk, AG and Almeida, D and Dufour, A and Mahajan, VB},
title = {Multi-omics liquid biopsy identifies mitochondrial dysfunction in geographic atrophy and supports the longevity-associated metabolite α-ketoglutarate as a therapeutic strategy.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.12.26347263},
pmid = {41891014},
abstract = {BACKGROUND: Mitochondrial dysfunction is an emerging metabolic hallmark of age-related diseases, yet tools to directly profile mitochondrial pathways and test metabolic interventions in the living human eye remain limited. Multi-omics ocular liquid biopsy enables real-time proteomic and metabolomic profiling of the intraocular microenvironment, complementing systemic biomarkers and imaging surrogates. Here, we used this approach to define mitochondrial and tricarboxylic acid (TCA) cycle dysregulation in geographic atrophy (GA) and to assess whether oral α-ketoglutarate (α-KG) supplementation can modulate mitochondrial metabolites within the eye.

METHODS: Mitochondrial and TCA cycle-related proteins were profiled in aqueous humor (AH) samples from patients with GA using DNA-aptamer-based proteomics. In a phase 0 study, a second cohort undergoing sequential cataract surgery provided paired AH samples collected at first-eye surgery and at second-eye surgery after interim α-KG supplementation. These samples underwent targeted metabolomic profiling using hydrophilic interaction liquid chromatography coupled with mass spectrometry.

RESULTS: In GA, 64 mitochondrial proteins were differentially expressed, including coordinated TCA-cycle deficiencies marked by reduced expression of enzymes regulating TCA entry and flux, including PDHB and DLST. In the phase 0 cohort, oral α-KG supplementation significantly increased intraocular α-KG levels and the α-KG-to-succinate ratio (P < 0.05), with coordinated shifts across TCA intermediates consistent with enhanced TCA cycle flux.

CONCLUSIONS: AH proteomics demonstrated mitochondrial pathway depletion in GA, consistent with reduced oxidative bioenergetic capacity. AH metabolomics provided first-in-human in vivo evidence that systemic α-KG supplementation can modify intraocular metabolites and may enhance intraocular energy metabolism. These findings support ocular liquid biopsy as a precision-health framework for per-patient biomarker-guided metabolic trials in GA.

PLAIN LANGUAGE SUMMARY: Geographic atrophy (GA) is an advanced form of age-related macular degeneration and a major cause of irreversible vision loss. To better understand the biology of GA, we studied proteins and small molecules in aqueous humor, the fluid inside the eye. We found that eyes with GA showed clear signs of mitochondrial dysfunction, including disruptions in the tricarboxylic acid (TCA) cycle, a key pathway for energy production. This suggests that impaired cellular metabolism is an important feature of the disease. We then tested whether oral α-ketoglutarate (α-KG), a metabolite involved in mitochondrial function and previously shown to have life-extending effects in preclinical studies, could alter these metabolic pathways in the human eye. We found that α-KG supplementation not only increased intraocular α-KG levels but changed metabolic markers linked to mitochondrial activity, providing the first direct evidence that oral supplementation can reach the eye and measurably modify metabolism inside the living human eye. Together, these findings show that liquid biopsy can provide a direct molecular snapshot of the living human eye and may help accelerate the development of biomarker-guided therapies for ocular diseases.

KEY POINTS: Questions: What specific mitochondrial and TCA-cycle dysfunctions occur in the aqueous humor (AH) of patients with geographic atrophy (GA), and can oral α-ketoglutarate (α-KG) supplementation measurably remodel these metabolic pathways in the living human eye?Findings: AH proteomics in GA patients revealed significant mitochondrial disruption and a coordinated depletion of TCA-cycle enzymes. In a paired-eye interventional metabolomics study, oral α-KG significantly increased intraocular α-KG levels and the α-KG-to-succinate ratio, proving that systemic therapy can drive measurable metabolic modulation within the human eye.Meaning: Multi-omics liquid biopsy provides a direct, eye-specific readout of mitochondrial metabolism in GA and offers early human proof-of-concept that a systemic metabolic therapy can successfully reach and modify intraocular pathways, paving the way for biomarker-guided clinical trials in AMD.},
}

@article {pmid41891097,
year = {2026},
author = {Gallardo, MJ and Porter, M and Vincent, L and Sandrosyan, A and Koch, B and Kasuga, DT},
title = {Outcomes of Ab-Interno Canaloplasty and Gonioscopy-Assisted Transluminal Trabeculotomy in Eyes with Sustained Intraocular Pressure Elevation Following Intravitreal Injections.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {563035},
pmid = {41891097},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the long-term efficacy and safety of combined ab-interno canaloplasty (ABiC) and gonioscopy-assisted transluminal trabeculotomy (GATT) with the iTrack microcatheter in patients with sustained intraocular pressure (IOP) elevation following intravitreal anti-VEGF or steroid injections.

PATIENTS AND METHODS: This was a retrospective, single-center study of patients who underwent ABiC and GATT with the iTrack microcatheter between 2017 and 2021 for secondary open-angle glaucoma or ocular hypertension following intravitreal injections. Eligible eyes had a preoperative IOP of ≥18 mmHg while on maximal tolerated medical therapy. Primary outcomes included IOP and glaucoma medication burden. Surgical success was defined using American Academy of Ophthalmology (AAO) criteria. Subgroup analyses were conducted by etiology (anti-VEGF vs steroid-induced). Kaplan-Meier analysis estimated cumulative success rates.

RESULTS: Thirty-four eyes from 30 patients were included, with a mean last follow-up of 15.3±9.8 months. Mean IOP was reduced by 46%, from 28.1±6.0 mmHg at baseline to 14.3±5.6 mmHg (p<0.001) at the last follow-up, while the number of medications decreased from 2.79±0.9 to 1.76±1.5 (p=0.001). Surgical success was achieved in 71% of eyes. Medication-free status was reached in 29% of eyes, compared with none at baseline, and 26% achieved IOP ≤15 mmHg without medications. Additional glaucoma procedures were needed in 11.8% of eyes. Combined ABiC and GATT remained effective in eyes receiving post-procedure intravitreal reinjections or prolonged topical steroid use. Kaplan-Meier analysis showed a survival probability above 70% at 25 months.

CONCLUSION: Combined ab-interno canaloplasty and GATT using the iTrack microcatheter is a safe surgical option for selected eyes with sustained IOP elevation following intravitreal injections. The procedure achieved meaningful reductions in IOP and medication use, including in eyes requiring continued intravitreal therapy, supporting a primary surgical effect. Careful patient selection and long-term follow-up remain essential, as a subset of eyes may require additional intervention.},
}

@article {pmid41891889,
year = {2026},
author = {Tabano, DC and Ali, FS and Borkar, DS and Leng, T and Ahmed, A and Ko, S and Myrick, A and Zwick, E and Downey, A and Barteselli, G and Singh, RP},
title = {One-year Real-world Outcomes With Faricimab in Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/23258160-20260302-02},
pmid = {41891889},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: This study evaluated real-world treatment patterns and 1-year outcomes in patients with neovascular age-related macular degeneration (nAMD) initiating faricimab.

PATIENTS AND METHODS: FARETINA-AMD was a retrospective study using data from the IRIS[®] Registry for patients diagnosed with nAMD initiating faricimab from February 2022 to March 2023.

RESULTS: Included in the study were 2,025 treatment-naive patients (2,184 eyes) and 22,253 patients (26,851 eyes) previously treated with anti-vascular endothelial growth factor (anti-VEGF) therapy. Visual acuity improved by 2.0 ± 15.0 (mean ± SD) letters in treatment-naive eyes (P < .001) and was maintained in previously treated eyes at injection 7. Central subfield thickness (CST) improved by -53.1 ± 64.8 μm in treatment-naive and -28.5 ± 79.7 μm in previously treated eyes (both P < .0001); 78.4% and 66.8%, respectively, had achieved/maintained CST ≤ 280 μm at injection 7. Dosing frequency was reduced in the second 6 months (mean 2.4-3.2 injections) versus the first 6 months (4.0-4.2) of treatment.

CONCLUSION: Outcomes among patients with nAMD receiving faricimab over 1-year follow-up support the real-world effectiveness and extended durability of treatment.},
}

@article {pmid41891912,
year = {2026},
author = {Antonietti, M and Mercado, C and Fortun, JA and Albini, TA and Dubovy, SR and Smiddy, WE and Schwartz, SG and Kovach, JL},
title = {Real-world Safety Profile of Avacincaptad Pegol in the Management of Geographic Atrophy.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-5},
doi = {10.3928/23258160-20260305-01},
pmid = {41891912},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: This study evaluated the safety of intravitreal avacincaptad pegol in treating geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

PATIENTS AND METHODS: A retrospective review was conducted of patients treated with avacincaptad pegol at Bascom Palmer Eye Institute from January 2024 to January 2025. Adverse events, side effects, and potential risk factors were recorded.

RESULTS: The study analyzed 124 eyes from 83 patients (mean age 81.8 ± 6.4 years; 49.4% male; 91.6% White) who received 409 injections in total. Injection intervals varied: 54 eyes monthly, 55 every other month, and others less frequently. The variability in injection frequency was mostly due to patient difficulty with follow-up. Follow-up ranged 3 to 12 months (median: 5 months). Baseline visual acuity averaged 0.40 (approx. 20/50 Snellen) decreasing slightly to 0.38 (20/53 Snellen)-not statistically significant (P = .628). Most eyes (85.2%) were pseudophakic; 47% of patients had prior neovascular AMD treated with anti-vascular endothelial growth factor (anti-VEGF), and 24.2% were simultaneously being treated for active neovascular AMD in the eye receiving avacincaptad pegol. Sixteen eyes had prior pegcetacoplan treatment. Adverse events were rare. One patient developed culture-negative endophthalmitis 4 days after the third injection, presenting with vision loss to hand motion but improving after intravitreal antibiotics. Side effects occurred in 14 eyes (13.8%) across 10 patients, including intraocular pressure elevation (seven eyes), discomfort (four eyes), visual disturbance (two eyes), and subconjunctival hemorrhage (one eye). Five patients discontinued treatment, and one eye (0.8%) had reactivation of neovascular AMD.

CONCLUSION: Our study highlights the safety profile of avacincaptad pegol for GA, with a low incidence of conversion to neovascular AMD, few adverse events, and manageable side effects.},
}

@article {pmid41892574,
year = {2026},
author = {Kim, SJ and Kim, DY and Jeong, D and Lee, C and Cho, HD and Kim, MP},
title = {Food-Grade Microgels for Age-Related Macular Degeneration: Design, Fabrication, and Targeted Delivery.},
journal = {Gels (Basel, Switzerland)},
volume = {12},
number = {3},
pages = {},
doi = {10.3390/gels12030252},
pmid = {41892574},
issn = {2310-2861},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is driven by complex pathophysiological processes, including oxidative stress, chronic inflammation, complement dysregulation, and vascular endothelial growth factor (VEGF)-mediated neovascularization. Nutritional interventions-particularly supplementation with carotenoids, omega-3 fatty acids, polyphenols, and essential micronutrients-have demonstrated clinical benefits in slowing disease progression, as evidenced by landmark trials such as AREDS and AREDS2. However, many AMD-relevant bioactives exhibit poor aqueous solubility, low chemical stability, and limited gastrointestinal bioavailability, which significantly constrain their therapeutic efficacy. Food-grade microgels have emerged as versatile colloidal delivery platforms capable of addressing these limitations through rational structural and physicochemical design. This review provides a systematic roadmap for developing food-grade microgels, organized into: (1) the molecular design of protein- and polysaccharide-based networks; (2) advanced fabrication strategies such as microfluidics and atomization; (3) spatiotemporal release programming within the gastrointestinal tract; and (4) multi-nutrient synergy for retinal protection. This approach highlights how controlled crosslinking, interfacial assembly, and tunable network architectures enhance nutrient stabilization. Particular emphasis is placed on spatiotemporal release programming within the gastrointestinal tract, including diffusion-limited gastric retention, pH- and bile-responsive swelling in the small intestine, and microbiota-triggered degradation in the colon. These mechanisms collectively enable region-specific release, improved micellar incorporation, enhanced systemic absorption, and more consistent retinal delivery. Furthermore, we discuss co-encapsulation strategies that accommodate both hydrophilic and lipophilic bioactives, thereby minimizing antagonistic interactions and enabling synergistic nutritional modulation of oxidative and inflammatory pathways implicated in AMD. A central novelty of this review is the integration of the gut-eye axis, framing microgel-based oral delivery as a systemic pathway to modulate retinal health via the intestinal environment. By bridging retinal disease biology with food colloid science, this review proposes food-grade microgels as a translational platform for next-generation nutraceutical interventions. The integration of programmable release behavior with clinically validated nutrient regimens offers a promising pathway toward more effective and mechanistically informed dietary management of AMD.},
}

@article {pmid41893318,
year = {2026},
author = {Greiner, JV and Glonek, T},
title = {Metabolomics of Ocular Tissues with High and Low Metabolic Activity.},
journal = {Metabolites},
volume = {16},
number = {3},
pages = {},
doi = {10.3390/metabo16030167},
pmid = {41893318},
issn = {2218-1989},
support = {EY-03988/EY/NEI NIH HHS/United States ; Grant 533181//Valerie and Walter Winchester Grant/ ; },
abstract = {BACKGROUND/OBJECTIVES: An unexplainably high millimolar (~3 mM) concentration of adenosine triphosphate (ATP), herein designated as nucleoside triphosphate (NTP), exists in the crystalline lens even though all of the known functions of NTP combined require only micromolar (μM) concentrations. Since the lens is one of the most metabolically quiescent tissues in the body and the retina is one of the most metabolically active tissues in the body, we compared their phosphorus metabolomics and related metabolic indices that measure their metabolic health status. As such, the purpose of this report was to compare the NTP concentrations in lenticular and retinal tissues and the metabolic indices that include NTP as well as their phosphorus-31 spectral modulus (PSM).

METHODS: Known phosphatic metabolic profiles of rat lenses and retinas were compared and quantified in mole % phosphorus using phosphorus-31 nuclear magnetic resonance spectroscopy. Metabolic indices measuring health status, where ATP is a principal component, were calculated, including the PSM.

RESULTS: In this secondary analysis, the NTP concentration calculated in the lens was 41.0% of the total phosphate detected, whereas it was similarly 37.6% in the sensory retina. The PSM values were 1.28 for the lens and similarly 1.42 for the retina.

CONCLUSIONS: Due to the lens tissue's low quiescent metabolic activity, one might expect the NTP concentration to be lower in the lens than in the highly metabolically active retina: a similar difference is expected in the PSM. However, this was not the case with the mM concentrations of NTP in both the lens (≥2.3 mM) and the retina (2.4 mM). The similarly high mM NTP concentration coupled with the PSM-calculated measure of metabolic health in these tissues is a novel finding. The novel findings of such similarly high concentrations of NTP in these metabolically diverse eye tissues further support and are consistent with the hypothesized role of NTP as a hydrotrope, preventing protein aggregation resulting in age-related cataractogenesis and age-related macular degeneration.},
}

@article {pmid41893888,
year = {2026},
author = {Azizmohammad Looha, M and Amanollahi, M and Hashemi, E and Jameie, M and Mohammadpoor, A and Mozafar, M and Samiee, R and Jalalinejad, M and Arevalo, JF},
title = {Global burden of age-related macular degeneration: Trends, regional disparities, and projections from the Global Burden of Disease study 2021.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {41893888},
issn = {1435-702X},
}

@article {pmid41893991,
year = {2026},
author = {Venugopal, D and Wood, J and Black, A and Bradley, C and Bentley, S},
title = {Development and Validation of the Assessment of Low Luminance Vision-Related Activities.},
journal = {Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {46},
number = {1},
pages = {81-89},
pmid = {41893991},
issn = {1475-1313},
mesh = {Humans ; Cross-Sectional Studies ; Aged ; Male ; Female ; *Visual Acuity/physiology ; Reproducibility of Results ; *Vision, Low/physiopathology/diagnosis ; Middle Aged ; *Vision, Binocular/physiology ; Aged, 80 and over ; *Vision Tests/methods ; Adult ; Psychometrics ; },
abstract = {PURPOSE: To develop a new comprehensive vision-related low luminance performance-based measure, the 'Assessment of Low Luminance Vision-Related Activities' (ALLVA), and evaluate its construct validity and test-retest reliability using Rasch analysis.

METHODS: A cross-sectional observational study of 75 adults with vision impairment from various ocular conditions (mean age 70 years [SD: 15 years]; mean binocular visual acuity 0.63 logMAR [SD: 0.45 logMAR]) was conducted. Seventeen tasks were developed as items and administered to participants under low luminance, with completion time and number of errors recorded. As some items could not be completed by all participants, five categories of completion time were created for analysis (quartiles and a fifth category representing non-completion). The 'method of successive dichotomisations'-a polytomous Rasch model that always estimates ordered response category thresholds, enabling its application to binned continuous data-was applied to create a single combined measure of performance. Errors were not analysed as they occurred infrequently and generally increased completion time. Eleven participants with age-related macular degeneration were retested after 2-4 weeks. Clinical vision measures, including visual acuity, contrast sensitivity and visual fields, were also collected.

RESULTS: Initial analysis of the 17-task ALLVA led to removal of one item, walking a mobility course, due to infit and outfit mean square statistics being outside the acceptable range. For the remaining 16 tasks, item difficulty was well targeted to person ability, with only a minor floor effect. Item and person reliability values were 0.98 and 0.93, respectively. Clinical vision measures were significantly correlated with person measures. Bland-Altman analysis indicated a mean difference between test and retest person measures of -0.08 logits (95% limits of agreement 2.16 to -2.32 logits).

CONCLUSION: The ALLVA is the first comprehensive vision-related low luminance performance-based measure. It demonstrated strong Rasch psychometric properties, validity and good test-retest reliability.},
}

Humans
Cross-Sectional Studies
Aged
Male
Female
*Visual Acuity/physiology
Reproducibility of Results
*Vision, Low/physiopathology/diagnosis
Middle Aged
*Vision, Binocular/physiology
Aged, 80 and over
*Vision Tests/methods
Adult
Psychometrics

@article {pmid41896032,
year = {2026},
author = {Chen, F and Shi, Y},
title = {Lipid peroxidation as a driver of oxidative and neuroinflammatory damage in ocular disease: review and perspectives.},
journal = {Archives of physiology and biochemistry},
volume = {},
number = {},
pages = {1-17},
doi = {10.1080/13813455.2026.2628183},
pmid = {41896032},
issn = {1744-4160},
abstract = {Context: Lipid peroxidation (LPO) causes oxidative stress and neuroinflammation in eye diseases. Malondialdehyde and 4-hydroxy-2-nonenal are produced in the eye via polyunsaturated fatty acid oxidation. Objective: Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. Materials and Methods: LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. Results: Electrophiles damage biological components. LPO damages the retina and optic nerve, causing age-related macular degeneration, diabetic retinopathy, and glaucoma. LPO also causes cataracts and dry eye in the anterior area. It also stimulates NLRP3 and NF-κB pathways, causing inflammation. Conclusion: Understanding how lipid peroxidation, oxidative stress, and neuroinflammation interact is crucial to developing effective eye health and vision loss therapies.},
}

@article {pmid41896127,
year = {2027},
author = {Zhao, X and Wen, Y and Yang, Z and Gu, X and Zeng, Y and Lai, A and Cao, W and He, M and Shi, Z and Zhang, W and Zhao, Q and Cheng, T and Meng, L and Wang, Y and Cheng, S and Wang, C and Liu, X and Yu, Q and Cai, X and Liu, G and Lu, L and Lv, L and Wei, W and Yuan, D and Zhang, J and Cun, Y and Chen, M and Zhang, T and Li, Z and Zeng, Q and Xiao, Z and Wang, C and Su, Y and Wang, Z and Sha, Q and Sheng, B and Chen, Y},
title = {Development and validation of a deep learning model to predict visual and anatomical prognosis of anti-VEGF therapy for neovascular age-related macular degeneration (KongMing Study): a prospective, nationwide, multicentre study.},
journal = {The Lancet. Digital health},
volume = {},
number = {},
pages = {100971},
doi = {10.1016/j.landig.2025.100971},
pmid = {41896127},
issn = {2589-7500},
abstract = {BACKGROUND: The financial burden and the uncertain response of the anti-vascular endothelial growth factor (anti-VEGF) treatment often cause hesitation among patients with neovascular age-related macular degeneration (nAMD), highlighting the need for a reliable method to predict treatment outcomes. We aimed to develop and validate a deep learning model that can predict the visual and anatomical prognosis of patients with nAMD undergoing anti-VEGF therapy.

METHODS: This prospective, nationwide, multicentre study involved 18 tertiary referral hospitals from 12 provinces across China. A large dataset of patients (aged 50-85 years) with nAMD treated with anti-VEGF therapy (Conbercept, 0·5 mg/0·05 mL, Chengdu, China) under a 3+PRN regimen was established. All participants underwent comprehensive ophthalmological examinations, including best-corrected visual acuity (BCVA) assessment and optical coherence tomography (OCT) imaging at baseline, follow-up, and 4-6 weeks after treatment. Patients with other ocular diseases that could confound the diagnosis or prognosis of nAMD were excluded. A Structural-Attention Guided Therapeutic Response Predicting Model (KongMing Model) was developed based on the lesion-aware, transformer-based multitask architecture to facilitate post-single-injection (4-6 weeks after any single injection during the treatment), post-three-loading-injections (4-6 weeks after the first three consecutive injections), and 1-year-post-three doses plus pro re nata (3+PRN; 1-year after treatment) dual predictions of visual and anatomical prognoses. For the prediction of BCVA changes, model performance was evaluated with the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, average precision, and human-machine comparison. The prediction of BCVA values was evaluated with mean absolute error (MAE) and coefficient of determination (R[2]). The prediction of post-treatment OCT images was evaluated by the structural similarity index measure (SSIM) compared with the true post-treatment OCT images. Heatmaps and Shapley additive explanation images were used to identify features related to the prognosis of nAMD.

FINDINGS: From July 1, 2020, to Dec 31, 2023, we collected 29 772 OCT images from 1226 participants after screening to form the internal dataset. From Jan 1, 2023, to May 1, 2024, we collected 3308 OCT images from 172 participants after screening to form the external dataset. In total, we included 603 (43·1%) women and 795 (56·9%) men. For the prediction of post-single-injection, post-three-loading-injections, and 1-year-post-3+PRN BCVA changes, our model achieved AUCs of 0·948 (95% CI 0·942-0·954) in the internal test and 0·941 (0·934-0·948) in the external test, also significantly outperforming ophthalmologists with different levels of experience in the human-machine comparison (all p<0·0001). For the prediction of the post-treatment BCVA values, our model had a remarkably low MAE across the three predictions (range 0·048 [0·039-0·057] to 0·058 [0·044-0·072]) and high R[2] (range 0·7140-0·9012) across both internal and external tests. The model achieved an SSIM exceeding 0·57, indicating a close similarity between the predicted and true post-treatment OCT images. In all aspects, our model outperformed the convolutional neural network-based models. Heatmaps and SHAP plots precisely located the features related to the prognosis of nAMD.

INTERPRETATION: The KongMing Model, developed and tested by a nationwide, multicentre dataset, showed excellent performance in predicting the post-single-injection, post-three-loading-injections, and 1-year-post-3+PRN visual and anatomical prognosis of patients with nAMD undergoing anti-VEGF therapy. It provides a robust and non-invasive method for more informed personalised treatment planning, potentially improving treatment adherence and avoiding unnecessary interventions.

FUNDING: National Natural Science Foundation of China, CAMS Innovation Fund for Medical Sciences, Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences, Lumitin Vision to Brightness Research Funding for the Young and middle-aged Ophthalmologists, Peking Union Medical College Hospital Talent Cultivation Program, Fundamental Research Funds for the Central Universities, Peking Union Medical College, National High-Level Hospital Clinical Research Funding, Beijing Students' Funding for Innovation and Entrepreneurship Training Program, Guangdong Basic and Applied Basic Research Foundation, Guangdong Provincial Key Laboratory.},
}

@article {pmid41896129,
year = {2027},
author = {Tsai, CY and Lai, TT},
title = {Artificial intelligence for post-treatment prediction in age-related macular degeneration.},
journal = {The Lancet. Digital health},
volume = {},
number = {},
pages = {100997},
doi = {10.1016/j.landig.2026.100997},
pmid = {41896129},
issn = {2589-7500},
}

@article {pmid41883753,
year = {2026},
author = {Vidal-Alaball, J and Arocas Bonache, A and Solé-Casals, J and Royo Fibla, D and Marin-Gomez, FX and Distéfano, LN and Boixadera, A and Casado-García, Á and García-Domínguez, M and Inés, A and Heras, J and Zapata, MA},
title = {Clinical validation of artificial intelligence algorithms for the detection of different central-involved retinal pathologies and glaucoma from non-mydriatic images.},
journal = {Frontiers in artificial intelligence},
volume = {9},
number = {},
pages = {1754682},
pmid = {41883753},
issn = {2624-8212},
abstract = {UNLABELLED: The use of Artificial intelligence (AI) algorithms for detecting different ophthalmic diseases, especially diabetic retinopathy (DR), has become increasingly popular. In this paper, we evaluate the screening performance of different AI algorithms based on convolutional neural networks (CNNs) in a real-world scenario. To that aim, we conducted an observational and cross-sectional study on patients aged ≥18 years with type-2 diabetes mellitus, who had undergone fundus examination for DR screening using a teleophthalmology program. We used the UPRETINA diagnostic system, which consists of 8 AI algorithms based on CNNs. A total of 1,652 eyes from 871 patients were analyzed. The AI algorithms had a sensitivity/specificity of 86.8%/95.6% for detecting DR; 94.9%/94.3% for detecting age-related macular degeneration (AMD); 82.7%/92.4% for detecting glaucomatous optic neuropathy (GON); 87.0%/87.5% for detecting epiretinal membrane; and 89.7%/98.0% for detecting nevus. Additionally, the sensitivity/specificity for correctly classifying images as right eye/left eye and to correctly classifying images gradeability (medium or high quality) were 100% /100 and 92.9%/90.5%, respectively. The AUROC of the AI algorithms ranged between 0.9777 (AMD) and 0.9122 (GON). UPRETINA system was capable of automatically and accurately classifying the screening retinographies, reducing workload and leading to a scenario of more efficient optimization of resources.

CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04132401 NCT04132401.},
}

@article {pmid41885533,
year = {2026},
author = {Michaud, C and Faurite, C and Guénot, J and Gallice, M and Chiquet, C and Vayssière, N and Berry, I and Trotter, Y and Baurès, R and Rosito, M and Soler, V and Peyrin, C and Cottereau, BR},
title = {Perceptual Learning as a Rehabilitation Approach to Enhance Motion Processing in Maculopathy Patients.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {3},
pages = {52},
doi = {10.1167/iovs.67.3.52},
pmid = {41885533},
issn = {1552-5783},
mesh = {Humans ; Male ; *Motion Perception/physiology ; Female ; *Macular Degeneration/rehabilitation/physiopathology ; Magnetic Resonance Imaging ; Aged ; *Learning/physiology ; Middle Aged ; Visual Acuity/physiology ; },
abstract = {PURPOSE: Macular degeneration (MD) is a disease affecting the central retina and significantly impairing vision. Given the absence of a cure, rehabilitation strategies are vital for enhancing visual perception.

METHODS: This study introduces a perceptual learning (PL) protocol for MD patients, focusing on improving motion perception, a key ability for navigating environments and social interactions. Patients underwent four weeks of motion discrimination training, with pretraining and post-training functional magnetic resonance imaging scans to study the underlying neural mechanisms. We also assessed generalization to an untrained multiobject tracking task in a subset of participants. A control group, matched by age and gender with simulated scotomata, followed the same procedures.

RESULTS: Results in both groups indicated improved motion discrimination and increased responses in the human middle temporal complex (hMT+), a critical neural hub for motion processing. Improvements in the multiobject tracking task suggested transferable learning effects.

CONCLUSIONS: These findings highlight perceptual learning as a promising rehabilitation strategy for MD and potentially other eye conditions.},
}

Humans
Male
*Motion Perception/physiology
Female
*Macular Degeneration/rehabilitation/physiopathology
Magnetic Resonance Imaging
Aged
*Learning/physiology
Middle Aged
Visual Acuity/physiology

@article {pmid41885545,
year = {2026},
author = {Zhang, K and Jia, L and Zhao, C and Wang, Y and Wei, P and Han, G},
title = {Genetic Evidence for Causal Effects of Blood Metabolites on Age-Related Macular Degeneration and its Subtypes.},
journal = {Translational vision science & technology},
volume = {15},
number = {3},
pages = {31},
doi = {10.1167/tvst.15.3.31},
pmid = {41885545},
issn = {2164-2591},
mesh = {Humans ; Mendelian Randomization Analysis ; *Macular Degeneration/genetics/blood/metabolism/classification ; Aged ; },
abstract = {PURPOSE: Age-related macular degeneration (AMD) is a predominant cause of permanent vision impairment among older individuals. Despite available treatments for advanced disease, a comprehensive understanding of the pathogenesis, specifically the pivotal causal pathways, remains elusive. This study aims to assess the causal effects of 1400 serum metabolites and their ratios on 3 AMD subtypes using Mendelian randomization (MR).

METHODS: This study leveraged an integrated MR analytical framework to systematically investigate the causal relationships of 1400 circulating metabolites and metabolite ratios with 3 AMD subtypes: early, dry, and wet AMD. The robustness and consistency of the findings were validated via comprehensive sensitivity analyses, alongside assessments for heterogeneity and horizontal pleiotropy.

RESULTS: Of the 1400 metabolites and metabolite ratios examined, inverse variance weighting identified 77, 62, and 80 metabolites with statistically significant causal associations with early, dry, wet AMD, respectively. Most of these associations demonstrated consistency across complementary MR methodologies. Furthermore, most of the identified metabolites did not show significant evidence of heterogeneity or horizontal pleiotropy. Notably, among lipid classes, glycerophosphoethanolamine (GPE) metabolites consistently exhibited protective effects.

CONCLUSIONS: Multiple metabolite classes, including glycerophospholipids, fatty acids, steroid hormones, and energy metabolism intermediates, are involved in AMD pathogenesis. These findings confirm that metabolic dysregulation is the principal driver of AMD at the causal level, in addition to revealing heterogeneous effect sizes of distinct metabolic pathways across disease subtypes. This study reveals potential molecular targets for developing strategies based on metabolism for AMD prevention, diagnosis, and precision therapeutics.

TRANSLATIONAL RELEVANCE: This work bridges fundamental metabolic discoveries to clinical application by identifying causal metabolites as novel therapeutic targets and informing strategies specific to disease subtypes for precision medicine and diagnostics in AMD.},
}

Humans
Mendelian Randomization Analysis
*Macular Degeneration/genetics/blood/metabolism/classification
Aged

@article {pmid41887320,
year = {2026},
author = {Boscia, G and Feo, A and Quarta, A and Stradiotto, E and Forte, P and Termite, AC and Mastropasqua, R and Savastano, A and Reibaldi, M and Eandi, CM and Boscia, F and Cicinelli, MV and Au, A and Tsui, E and Vujosevic, S and Schmidt-Erfurth, U and Sarraf, D and Sadda, SR and Romano, MR and Borrelli, E and Viggiano, P},
title = {Intraretinal Hyperreflective Foci: Pathophysiology, Imaging Features, and Clinical Implications Across Retinal Diseases.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101464},
doi = {10.1016/j.preteyeres.2026.101464},
pmid = {41887320},
issn = {1873-1635},
abstract = {Intraretinal hyperreflective foci (IHRF) are a common but pathologically diverse optical coherence tomography (OCT) finding, increasingly recognized as a hallmark of retinal disease activity. IHRF have been described in age-related macular degeneration (AMD), where they may represent migrating retinal pigment epithelium cells, in diabetic retinopathy, retinal vein and artery occlusions, pachychoroid spectrum disorders, inherited retinal dystrophies, and ocular inflammatory diseases. Their appearance reflects a spectrum of underlying processes, including inflammatory cell recruitment, lipid or proteinaceous material deposition, and degenerative tissue remodeling. Advances in OCT technology and multimodal imaging have refined the characterization of IHRF, enabling correlations with histopathology, cytokine profiles, and genetic risk variants. Across diseases, their presence, number, distribution, and temporal evolution have been linked to structural progression, functional decline, and treatment response-serving as early indicators of atrophy or neovascularization in AMD, markers of inflammation and therapeutic responsiveness in vascular retinopathies, and predictors of recurrence or complication in pachychoroid disease. This review provides a comprehensive synthesis of the current literature on IHRF, summarizing their proposed histopathological correlates, multimodal imaging features, molecular associations, prognostic significance, and potential role as biomarkers in a wide range of retinal disorders.},
}

@article {pmid41876602,
year = {2026},
author = {Steiner, S and Gerendas, BS and Deak, G and Leingang, O and Whitby, A and Bogunovic, H and Reiter, GS and Schmidt-Erfurth, U},
title = {Correlation between human expert macular fluid height assessment and fluid volume quantification in neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-44982-8},
pmid = {41876602},
issn = {2045-2322},
abstract = {To investigate the association between manually measured retinal fluid heights and AI-quantified retinal fluid volumes and to explore disease activity indicated by fluid volume distributions in neovascular age-related macular degeneration (nAMD) using an approved AI-based algorithm. This retrospective study analyzed baseline OCT data from a multicenter nAMD cohort. Manually measured maximum macular fluid heights on B-scans in the central millimeter (CMM) for intraretinal fluid (IRF), subretinal fluid (SRF), and pigment epithelial detachment (PED) were compared with vertical fluid heights and three-dimensional volumes obtained by automated quantification using an AI-based tool (RetInSight Fluid Monitor Version 2). Out of 890 eyes, IRF was identified in the CMM in 328 eyes, SRF in 502 eyes, and PED in 705 eyes. The correlation between manual and AI-based height measurements was strong for IRF (r = 0.87) and PED (r = 0.91), and moderate for SRF (r = 0.67). Manual height-AI volume correlations within the CMM were strong for IRF (r = 0.76) and PED (r = 0.87), and moderate for SRF (r = 0.55). These correlations decreased when total fluid volumes within the central 6 mm were compared with manual CMM height, indicating that CMM height does not represent total nAMD disease activity. In conclusion, AI-derived and manual height measurements showed strong agreement for IRF and PED and moderate agreement for SRF. Maximum fluid height did not reliably reflect overall fluid volume or spatial distribution. AI-based retinal fluid assessment enables quantitative, whole-volume evaluation of retinal fluid and provides a measure of nAMD disease activity.},
}

@article {pmid41876676,
year = {2026},
author = {Shenoy, R and Monachan, MT and Gruszka-Goh, M and McKibbin, M},
title = {The Royal College of Ophthalmologists National Ophthalmology Database age-related macular degeneration (AMD) audit: report 1, associations with socio-economic deprivation in neovascular AMD.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41876676},
issn = {1476-5454},
support = {ACF-2023-11-004//DH | National Institute for Health Research (NIHR)/ ; },
abstract = {BACKGROUND: Early diagnosis and treatment of neovascular age-related macular degeneration (NvAMD) improve vision outcomes. This analysis investigates associations of English indices of multiple deprivation 2019 (IMD2019) with baseline characteristics, key care processes and visual acuity (VA) outcomes for NvAMD in the National Ophthalmology Database (NOD).

METHODS: Eligible eyes started treatment for NvAMD in England between 01/04/2020 and 31/03/2023. Participating centres with ≥25 eyes with baseline VA and IMD2019 data were included.

RESULTS: Eligible for analysis were 48,583 eyes from 60 English centres. Between decile 1 (most deprived) and decile 10 (least deprived), median age at start of treatment ranged from 79 to 82 years and median baseline VA ranged from 56 to 60 ETDRS letters. After one year of treatment (-28 to +84 days), the median number of injections administered ranged from 7 to 8 across deciles. Loss to follow-up was observed in 13.7% eyes in decile 1, and 11.8% in decile 10. Median VA at 12 months ranged from 61 to 65 ETDRS letters across deciles. A "good" VA outcome (≥70 ETDRS letters) was achieved by 45.5% in decile 10, compared with 35.9% observed in decile 1 (p < 0.001). A "poor" VA outcome (≥10 ETDRS letter loss from baseline) occurred in 18.4% of eyes in decile 1 versus 14.5% in decile 10 (p < 0.001).

CONCLUSIONS: Patients starting NHS-funded treatment in England for NvAMD and living in areas of higher socioeconomic deprivation were typically younger, had lower baseline acuity and achieved worse VA outcomes than those from lower deprivation areas, with little variation in treatment between the deciles.},
}

@article {pmid41877040,
year = {2026},
author = {Kocamış, Ö},
title = {Association between optical coherence tomography biomarkers and systemic inflammatory indices in neovascular age-related macular degeneration.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04753-5},
pmid = {41877040},
issn = {1471-2415},
}

@article {pmid41877687,
year = {2025},
author = {Hayat, B and Alone, DP},
title = {Unfolded proteins and aggregates: The role of proteostasis in pseudoexfoliation pathology.},
journal = {Molecular vision},
volume = {31},
number = {},
pages = {463-484},
pmid = {41877687},
issn = {1090-0535},
mesh = {Humans ; *Exfoliation Syndrome/metabolism/pathology ; *Proteostasis ; *Unfolded Protein Response ; *Protein Aggregates ; Animals ; Autophagy ; *Protein Aggregation, Pathological/metabolism/pathology ; Proteasome Endopeptidase Complex/metabolism ; Ubiquitin/metabolism ; Endoplasmic Reticulum Stress ; Protein Folding ; Aging/metabolism ; },
abstract = {BACKGROUND: Proteostasis impairment is central to cellular dysfunction in protein aggregation disorders such as Alzheimer disease, Parkinson disease, and age-related macular degeneration. Pseudoexfoliation (PEX), a systemic age-related disorder and a leading cause of secondary glaucoma, is increasingly recognized as a protein aggregation disease. It is characterized by the deposition of pseudoexfoliative material (PEXM) in ocular tissues, leading to elevated intraocular pressure and optic neuropathy.

OBJECTIVE: This review synthesizes current evidence on the role of proteostasis failure in PEX pathogenesis, with a focus on molecular mechanisms, stress response pathways, and potential therapeutic interventions.

METHODS: We conducted a comprehensive literature review of studies examining proteostasis mechanisms in PEX. Emphasis was placed on cellular pathways regulating protein synthesis, folding, and degradation, including the unfolded protein response (UPR), ubiquitin-proteasome system (UPS), and autophagy, as well as environmental and aging-related triggers of proteotoxic stress.

RESULTS: Evidence indicates that chronic proteotoxic stress, arising from aging, oxidative damage, and environmental influences, disrupts the proteostasis network (PN). Dysregulation of ER stress signaling, cytosolic stress responses, and protein degradation pathways contributes to the accumulation of misfolded proteins and extracellular matrix deposits in ocular tissues. These molecular alterations underlie disease onset and progression in PEX syndrome (PEXS) and PEX glaucoma (PEXG).

CONCLUSIONS: Proteostasis dysfunction plays a pivotal role in PEX pathogenesis by promoting protein misfolding, aggregation, and extracellular deposition. Targeting the proteostasis network, through modulation of stress responses and enhancement of degradation pathways, represents a promising therapeutic strategy for PEXS and PEXG.},
}

Humans
*Exfoliation Syndrome/metabolism/pathology
*Proteostasis
*Unfolded Protein Response
*Protein Aggregates
Animals
Autophagy
*Protein Aggregation, Pathological/metabolism/pathology
Proteasome Endopeptidase Complex/metabolism
Ubiquitin/metabolism
Endoplasmic Reticulum Stress
Protein Folding
Aging/metabolism

@article {pmid41878122,
year = {2026},
author = {Gong, J and Wang, P and Xu, Y and Xia, X},
title = {Nanotechnology-Based Treatment for Ophthalmic Diseases.},
journal = {International journal of nanomedicine},
volume = {21},
number = {},
pages = {597696},
pmid = {41878122},
issn = {1178-2013},
mesh = {Humans ; *Eye Diseases/drug therapy/therapy ; *Nanomedicine/methods ; Animals ; Drug Delivery Systems/methods ; *Nanotechnology/methods ; Nanoparticles/chemistry ; Genetic Therapy/methods ; Nanoparticle Drug Delivery System ; },
abstract = {Eye diseases are a major global public health issue causing vision impairment and blindness. The eye's physiological barriers limit traditional drug delivery methods, resulting in low bioavailability, high risks, and poor patient compliance. Nanotechnology offers a revolutionary solution that can enhance the abilities of drugs in corneal retention, barrier penetration, targeted delivery and controlled release to improve efficacy and reduce side effects.This paper reviews the latest advances in nanotechnology for treating ophthalmic diseases. It covers primary nanocarrier systems (lipid, polymeric, carbon-based, and metallic/metallic compound nanoparticles), detailing their characteristics and ocular application potential. It also focuses on specific applications: nanomedicine for anterior segment disorders (cataracts, dry eye, inflammatory conditions) and posterior segment diseases (age-related macular degeneration, diabetic retinopathy, retinal vein occlusion), breakthroughs in delivering anti-VEGF drugs, and innovative applications in treating refractory ocular tumors. Additionally, it explores nanotechnology's prospects in ocular tissue regeneration and retinal gene therapy. Finally, the paper discusses challenges in clinical translation, including standardization, biosafety evaluation, and regulatory approval, and offers an outlook for future development.},
}

Humans
*Eye Diseases/drug therapy/therapy
*Nanomedicine/methods
Animals
Drug Delivery Systems/methods
*Nanotechnology/methods
Nanoparticles/chemistry
Genetic Therapy/methods
Nanoparticle Drug Delivery System

@article {pmid41878598,
year = {2026},
author = {D'Souza, PR and Sugathan, A},
title = {Charles bonnet syndrome with subsequent depression in acute angle-closure glaucoma: a case report.},
journal = {Oxford medical case reports},
volume = {2026},
number = {3},
pages = {omag024},
pmid = {41878598},
issn = {2053-8855},
abstract = {Charles Bonnet syndrome (CBS) presents with complex visual hallucinations in visually impaired individuals with preserved insight. While most commonly associated with macular degeneration, it may occur in glaucoma. CBS is often under-reported due to stigma and may progress to psychiatric morbidity. A 63-year-old man with bilateral visual loss following acute angle-closure glaucoma experienced vivid hallucinations of animals and snakes. Initially concealed due to embarrassment, the symptoms were revealed during psychiatric assessment. Ophthalmic evaluation confirmed glaucomatous changes; MRI brain was recommended but declined. CBS was diagnosed, and hallucinations resolved with reassurance and low-dose clonazepam. Several weeks later, the patient developed moderate depression (HAM-D = 18), successfully treated with mirtazapine. At three months, he remained asymptomatic. This case is unusual for its association of CBS with angle-closure glaucoma and subsequent depression, underscoring the need for proactive inquiry, de-stigmatization, and integrated ophthalmic-psychiatric care.},
}

@article {pmid41878622,
year = {2026},
author = {Zhang, B and Tian, F and Hu, X and Hu, Y and Li, W},
title = {Expression Characteristics of Soluble sCD13 in Wet Age-Related Macular Degeneration and Its Diagnostic Value and Correlation Study.},
journal = {International journal of general medicine},
volume = {19},
number = {},
pages = {553165},
pmid = {41878622},
issn = {1178-7074},
abstract = {OBJECTIVE: This study explored the level of soluble CD13 (sCD13) and its correlation with angiogenic factors, evaluating the predictive efficacy of sCD13 in wet age-related macular degeneration (wAMD).

METHODS: 200 patients were included (58 in Non AMD group, 42 in Early AMD group, and 100 in wAMD group). Detailed routine and ophthalmologic examinations were performed on all subjects, and the central retinal thickness (CRT) and ganglion cell-inner plexiform layer (GCIPL) were determined. The concentration of sCD13 was compared. The correlation of sCD13 with PDGF, hsCRP and IL-8 was analyzed. ROC curves were plotted and the diagnostic value of sCD13 was assessed by area under the curve (AUC).

RESULTS: The sCD13 concentration of patients in the wAMD group (20.41 ± 5.86 U/mL) was higher. Age, history of smoking, CRT, hsCRP and IL-8 were higher in the wAMD group, while mean GCIPL, BCVA, and PDGF were lower. sCD13 was positively correlated with hsCRP (r = 0.505) and IL-8 (r = 0.193) and negatively correlated with PDGF (r = -0.241). sCD13 had predictive efficacy in distinguishing wAMD from non AMD and early AMD, with AUC values of 0.74 and 0.61, respectively (P < 0.05).

CONCLUSION: sCD13 concentration in the affected eyes of wAMD patients is abnormally elevated and associated with elevated serum hsCRP and IL-8 levels and decreased PDGF. These results suggest that elevated sCD13 may promote the development of wAMD, emphasizing the importance of early control of sCD13 levels.},
}

@article {pmid41879246,
year = {2026},
author = {Pu, J and Gao, L and Thomas, TN and Goerdt, L and Corradetti, G and Kar, D and McGwin, G and Crosson, JN and Owsley, C and Curcio, CA},
title = {Choriocapillaris Flow Signal Deficits Are Associated With AMD Onset and Early Progression Over Three Years: ALSTAR2 Follow-Up.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {3},
pages = {51},
doi = {10.1167/iovs.67.3.51},
pmid = {41879246},
issn = {1552-5783},
mesh = {Humans ; Disease Progression ; Male ; Female ; Aged ; *Choroid/blood supply ; Tomography, Optical Coherence/methods ; Follow-Up Studies ; Fluorescein Angiography/methods ; Middle Aged ; *Macular Degeneration/physiopathology/diagnosis ; Regional Blood Flow/physiology ; Aged, 80 and over ; *Capillaries/physiopathology ; *Retinal Vessels/physiopathology ; },
abstract = {PURPOSE: To determine if a baseline choriocapillaris flow signal deficits (CCFD%), as a marker of impaired transport, is associated with age-related macular degeneration (AMD) onset and progression at the 3-year follow-up.

METHODS: Participants ≥ 60 years old with normal macular health, early AMD (eAMD), and intermediate AMD (iAMD) were staged at baseline and follow-up with the Age-Related Eye Disease Study (AREDS) 9-step classification system and were then classified as stable and progressing based on whether their stage advanced. Spectral-domain optical coherence tomography angiography (OCTA) quantified baseline CCFD% across the Early Treatment Diabetic Retinopathy Study (ETDRS) central subfield (CS), inner ring (IR), and an outer area (OA, extending superiorly). Adjusted baseline CCFD% values were compared between stable and progressing eyes.

RESULTS: Of 332 included eyes at baseline (mean age, 71.1 ± 5.8 years), 173 eyes were normal, 101 were eAMD, and 58 were iAMD. Over 3 years, 284 eyes remained stable (85.5%), and 48 eyes progressed (14.5%). In the overall cohort, progressing eyes demonstrated significantly higher baseline CCFD% than stable eyes in the CS (57.7% vs. 53.5%; P = 0.007) and IR (56.1% vs. 53.9%; P = 0.045), but not in the OA. When stratified by baseline AMD stage, stable versus progressor differences were exclusively observed in eAMD (51.4% vs. 60.7% and 52.6 vs. 58.0% for CS and IR, respectively) but not in OA or in normal eyes (all P > 0.05).

CONCLUSIONS: CCFD% in the CS and IR, one aspect of impaired transport between circulation and photoreceptors, is associated with AMD progression in early-stage disease; this spatial specificity implicates the fovea.},
}

Humans
Disease Progression
Male
Female
Aged
*Choroid/blood supply
Tomography, Optical Coherence/methods
Follow-Up Studies
Fluorescein Angiography/methods
Middle Aged
*Macular Degeneration/physiopathology/diagnosis
Regional Blood Flow/physiology
Aged, 80 and over
*Capillaries/physiopathology
*Retinal Vessels/physiopathology

@article {pmid41879420,
year = {2026},
author = {Lishinsky-Fischer, N and Jaskoll, S and Kramer, A and Grunin, M and Elbaz-Hayoun, S and Rinsky, B and Chowers, I and Levy, J},
title = {Distinct Genetic Profiles Associated With Subretinal Drusenoid Deposits and Cardiovascular Risk in Age-Related Macular Degeneration.},
journal = {Translational vision science & technology},
volume = {15},
number = {3},
pages = {27},
doi = {10.1167/tvst.15.3.27},
pmid = {41879420},
issn = {2164-2591},
mesh = {Humans ; *Macular Degeneration/genetics/complications ; Female ; *Retinal Drusen/genetics ; Male ; Aged ; Retrospective Studies ; *Polymorphism, Single Nucleotide ; *Cardiovascular Diseases/genetics ; Aged, 80 and over ; Middle Aged ; Tomography, Optical Coherence ; Genetic Predisposition to Disease ; Gene Frequency ; Genotype ; Risk Factors ; Phenotype ; },
abstract = {PURPOSE: Subretinal drusenoid deposits (SDDs) are increasingly recognized as a distinct phenotype in age-related macular degeneration (AMD) and may be linked to cardiovascular disease (CVD). This study aims to explore whether AMD patients with SDDs carry a distinct genetic profile related to CVD risk compared to those without SDDs.

METHODS: In a retrospective cohort of 459 AMD patients with genotyping and spectral-domain OCT data, we annotated SDD status and extracted cardiovascular diagnoses and procedures from electronic medical records. Fifty-two AMD-associated single-nucleotide polymorphisms (SNPs) were used to calculate weighted genetic risk scores (GRSs), and minor allele frequencies (MAFs) were compared between groups. Principal component analysis (PCA) was performed to assess clustering by SDD status within CVD subgroups.

RESULTS: Patients with SDDs exhibited distinct MAFs in several SNPs, including CFH, ARMS2, COL4A3, and ARHGAP21. Certain variants were more strongly associated with cardiovascular subtypes in patients with SDDs compared to those without. GRSs related to lipid metabolism and complement pathways were higher among SDD-positive patients within selected CVD subgroups. PCA suggested modest but significant separation between genetic profiles of patients with and without SDDs.

CONCLUSIONS: AMD patients with SDDs show distinct genetic signatures potentially relevant to cardiovascular health. These findings suggest that SDDs may represent a genetically and systemically unique AMD phenotype. Further investigation is warranted to understand the shared pathophysiology and potential for systemic risk stratification.

TRANSLATIONAL RELEVANCE: Integrating OCT phenotyping and genomic profiling in AMD may uncover systemic disease associations with implications for precision medicine.},
}

Humans
*Macular Degeneration/genetics/complications
Female
*Retinal Drusen/genetics
Male
Aged
Retrospective Studies
*Polymorphism, Single Nucleotide
*Cardiovascular Diseases/genetics
Aged, 80 and over
Middle Aged
Tomography, Optical Coherence
Genetic Predisposition to Disease
Gene Frequency
Genotype
Risk Factors
Phenotype

@article {pmid41879644,
year = {2026},
author = {Capuano, V and Fragiotta, S and Abadou, J and Sacconi, R and Miere, A and Amoroso, F and Souied, EH and Querques, G},
title = {Centenarian patients with neovascular age-related macular degeneration.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004837},
pmid = {41879644},
issn = {1539-2864},
abstract = {PURPOSE: To report clinical characteristics of exudative neovascular age-related macular degeneration (AMD) in centenarian patients.

METHODS: A retrospective, longitudinal study conducted in two retinal referral centers in Europe. Clinical characteristics of neovascular AMD patients having at last follow up at least ≥ 100 years were reviewed.

RESULTS: Twenty-eight eyes from 14 patients (13 females), with a mean baseline age of 95.7 (SD 4.1) years and a mean follow-up duration of 89 months (39.9). The mean age at last follow-up was 102.4 (1.7) years. Most eyes (86%) presented type 1 macular neovascularization (MNV). At the last follow-up, best corrected visual acuity (BCVA) was stable or improved in 57% of eyes, with a mean final BCVA of 53 letters (21.8) Snellen equivalent 20/100. Eyes with better visual outcomes (>50 letters) had significantly higher baseline BCVA (p<0.001) and thicker subfoveal choroidal thickness (p=0.03). Macular hemorrhage (25%) and macular atrophy (53.6%) were associated with poorer BCVA.

CONCLUSION: Centenarian patients with neovascular AMD can maintain vision with long-term anti-VEGF therapy. These findings underscore the need for tailored management strategies for the challenges faced by centenarians with neovascular AMD.},
}

@article {pmid41880726,
year = {2026},
author = {Karapapak, M and Özal, E and Ermiş, S and Önal, I and Gül, C and Özal, SA},
title = {Prevalence and progression of non-exudative macular neovascularization in age-related macular degeneration.},
journal = {Journal francais d'ophtalmologie},
volume = {49},
number = {4},
pages = {104835},
doi = {10.1016/j.jfo.2026.104835},
pmid = {41880726},
issn = {1773-0597},
abstract = {PURPOSE: To determine the prevalence of non-exudative macular neovascularization (neMNV) in age-related macular degeneration (AMD) and to identify potential markers for activation and disease progression using findings from optical coherence tomography angiography (OCTA).

MATERIALS AND METHODS: This retrospective longitudinal study included patients with treatment-naïve neMNV secondary to AMD who presented to a tertiary retina clinic between January 2021 and July 2024. Patients were evaluated using OCT and OCTA at each visit, with a definitive diagnosis of neMNV established using OCTA. Exclusion criteria included prior anti-VEGF therapy, pachychoroid spectrum diseases, vitreoretinal surgery, chorioretinal conditions, and unreliable OCTA images. Parameters assessed included best-corrected visual acuity (BCVA), and lens status.

RESULTS: neMNV was identified in 186 out of 3119 patients (5.96%). The mean age was 72.73±8.60 years, with a mean follow-up of 22.11±7.51 months. Transition from the non-exudative to the exudative form occurred in 34 (18.3%) patients, with an average activation duration of 14.71±8.42 months. BCVA improved significantly in neMNV eyes over time (P<0.01) but remained stable in fellow eyes. No significant correlations were found between activation time and age, gender, or laterality. The prevalence of exudative MNV in fellow eyes was 67%.

CONCLUSIONS: neMNV is relatively common among AMD patients, with a prevalence of 5.96%. Regular monitoring using OCTA is essential for early detection and management, given the significant potential for these lesions to progress to an exudative state. Future research should focus on identifying specific biomarkers and imaging characteristics predictive of neMNV activation.},
}

@article {pmid41881234,
year = {2026},
author = {Goerdt, L and Basten, V and Terheyden, JH and Dunbar, H and Luhmann, U and Zakaria, N and Leal, S and Moll, KP and Poor, S and Tufail, A and Schmid, M and Finger, RP and Schmitz-Valckenberg, S and Holz, FG and Saßmannshausen, M and , },
title = {Hyperreflective foci contiguous with the RPE associate with visual function in aging, early and intermediate AMD: MACUSTAR study report.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.03.020},
pmid = {41881234},
issn = {1879-1891},
abstract = {PURPOSE: To evaluate the association of hyperreflective foci contiguous with the retinal pigment epithelium (rpeHRF) with visual function impairment in aged normals, early (e) age-related macular degeneration (AMD), and intermediate (i) AMD.

DESIGN: Prospective cohort study.

SUBJECTS: Participants of the MACUSTAR study.

METHODS: MACUSTAR participants underwent color fundus photography, optical coherence tomography (OCT) imaging, best-corrected visual acuity (BCVA), low luminance VA (LLVA), rod-mediated dark adaptation (RMDA) at 12°, contrast sensitivity (CS), mesopic, and scotopic pointwise sensitivity deviation (mesPSD, scPSD) testing. rpeHRF presence and count were determined using custom FiJi software. Group comparisons and associations with visual function were analyzed using ANOVA, linear regression, and Spearman correlation.

MAIN OUTCOME MEASURES: Presence, burden, topographic distribution of rpeHRF; association with functional parameters.

RESULTS: Fifty-six normal aged (33 female (f), mean age 68.1 ± 6.4 years), 34 eAMD (27 f, 71.7 ± 6.4 years), and 583 iAMD eyes (387 f, 72.0 ± 7.0 years) were included. rpeHRF counts were 0.16 ± 0.85 in normals, 0.33 ± 0.96 in eAMD, and 1.61 ± 2.49 in iAMD (p < 0.001). BCVA, LLVA, CS (all p < 0.001), and scPSD (p = 0.001) differed between disease groups. Whereas RMDA and mesPSD did not. In iAMD, eyes with rpeHRF showed worse BCVA, LLVA, CS, scPSD (all p < 0.001), and mesPSD (p = 0.02). rpeHRF cound associated modestly with only CS, scPSD, LLVA, and BCVA.

CONCLUSIONS: Presence and burden of rpeHRF were independently associated with impaired visual function and may thus serve as a prognostic biomarker for disease progression and enrichment criterion for future interventional trials.},
}

@article {pmid41881262,
year = {2026},
author = {Yasuda, H and Nakamura, S and Shirakawa, A and Kuse, Y and Mori, K and Shimazawa, M},
title = {Age-dependent induction of ER stress in retinal pigment epithelium impairs phagocytosis via ADAM17-dependent MERTK shedding.},
journal = {The Journal of biological chemistry},
volume = {},
number = {},
pages = {111397},
doi = {10.1016/j.jbc.2026.111397},
pmid = {41881262},
issn = {1083-351X},
abstract = {Retinal pigment epithelium (RPE) plays a crucial role in maintaining visual function by phagocytosing photoreceptor outer segments (POS). Age-related decline in RPE phagocytic activity has been linked to the development of degenerative retinal diseases, including age-related macular degeneration (AMD). However, the underlying mechanisms of RPE phagocytic dysfunction remain poorly understood. In this study, we examined age-related induction of endoplasmic reticulum (ER) stress in RPE cells and its association with POS phagocytosis using tissues from middle-aged mice and cultured RPE cells. In the RPE-choroid complex of 12-month-old mice, ER stress marker proteins were significantly upregulated compared to younger mice. Notably, this increase was absent in the neural retina at the same age. In cultured RPE cells, pharmacological induction of ER stress by tunicamycin (Tm) significantly reduced both phagocytic activity and lysosomal function. Treatment with sodium 4-phenylbutyrate, a chemical chaperone, and transfection with chaperone protein-inducible plasmids alleviated the ER stress-induced phagocytic dysfunction in RPE cells. In the lysates of ER stress-induced RPE cells, the extracellular domain of Mer tyrosine kinase receptor (MERTK) and phosphorylation of focal adhesion kinase were significantly decreased. Mechanistically, ER stress promoted the maturation of a disintegrin and metalloprotease 17 (ADAM17) through Ca[2+]-dependent activation of the Furin protease, leading to MERTK shedding. Furthermore, ADAM17 knockdown attenuated the Tm-induced impairment of POS internalization. Collectively, our findings suggest that ER stress impairs RPE phagocytosis through an integrated mechanism and may contribute to the pathogenesis of AMD.},
}

@article {pmid41881267,
year = {2026},
author = {Dong, H and Ding, Q and Liu, M},
title = {Exploring the causal link between long-term elevated plasma caffeine levels and age-related eye diseases using Mendelian randomization.},
journal = {Experimental gerontology},
volume = {},
number = {},
pages = {113106},
doi = {10.1016/j.exger.2026.113106},
pmid = {41881267},
issn = {1873-6815},
abstract = {OBJECTIVE: Experimental evidence suggests that caffeine has the potential to reduce the risk of age-related eye diseases (AREDs). However, there is a lack of population-based evidence directly assessing whether long-term caffeine exposure benefits these conditions. In this study, we employ Mendelian randomization (MR) to evaluate the causal effects of long-term elevated plasma caffeine levels (PCL) on AREDs, including age-related macular degeneration (AMD), age-related cataract (ARC), and glaucoma.

METHODS AND ANALYSIS: Single-nucleotide polymorphisms strongly associated with PCL and located near the CYP1A2 and AHR genes, both key in caffeine metabolism, were selected as instrumental variables. The MR analyses then calculated the Wald ratio for each variant, with variant-specific estimates combined through a multiplicative random effects meta-analysis.

RESULTS: Our MR analysis showed that higher genetically predicted PCL were significantly associated with a reduced risk of dry AMD (odds ratio [OR], 0.651; 95% confidence interval [CI], 0.527-0.805; pFDR < 0.001), wet AMD (OR, 0.582; 95% CI, 0.433-0.781; pFDR = 0.001), ARC (OR, 0.812; 95% CI, 0.720-0.916; pFDR = 0.001), and primary open-angle glaucoma (POAG) (OR, 0.753; 95% CI, 0.633-0.896; pFDR = 0.002). Notably, an estimated 54.05% (95% CI: 19.25%-88.84%) of the protective effect of PCL on POAG was mediated through reduced intraocular pressure (IOP).

CONCLUSION: This MR study provides evidence that long-term higher plasma caffeine levels may reduce the risk of age-related eye diseases, including AMD, ARC, and POAG. Notably, approximately half of the protective effect of PCL on POAG is mediated through IOP reduction.

This study provides novel evidence on the long-term effects of caffeine on age-related eye diseases, including age-related macular degeneration (AMD), age-related cataract (ARC), and primary open-angle glaucoma (POAG). Unlike previous studies that used imprecise measures of caffeine exposure, such as caffeinated beverage intake, we utilized fasting plasma caffeine levels, offering a more accurate assessment of individual exposure. Through Mendelian randomization, we demonstrate that long-term caffeine exposure is independently associated with reduced risks of AMD and ARC, and is also linked to a lower risk of POAG, with approximately half of this effect mediated through intraocular pressure (IOP) reduction. Our findings suggest that caffeine could play a protective role in ocular health, offering new insights into potential prevention strategies for age-related eye diseases.},
}

@article {pmid41872539,
year = {2026},
author = {Gurumoorthy, D and Riotto, E and Faes, L and Spooner, K and Fu, DJ},
title = {Infographic: AREDS[1]&AREDS[2]-oral supplementation with antioxidants for age-related macular degeneration (AMD).},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {41872539},
issn = {1476-5454},
}

@article {pmid41873297,
year = {2026},
author = {Katsanos, A and Benekos, K and Karavasili, M and Gorgoli, K and Kostoulas, C and Gartzonika, K and Christodoulou, DK and Katsanos, K and Georgiou, I},
title = {Intestinal Microbiome of Newly Diagnosed Patients With Neovascular Age-Related Macular Degeneration: A 16S rRNA Gene Sequencing Study.},
journal = {Cureus},
volume = {18},
number = {2},
pages = {e103984},
pmid = {41873297},
issn = {2168-8184},
abstract = {BACKGROUND: This study aims to explore differences in the intestinal microbiome between patients with newly diagnosed neovascular age-related macular degeneration (AMD) and controls using 16S rRNA gene sequencing.

METHODOLOGY: In this cross-sectional study, stool samples from newly diagnosed White patients with neovascular AMD and controls were used for the assessment of the intestinal microbiome. The DNeasy PowerSoil Pro Kit (QIAGEN, Hilden, Germany) was used to extract microbial DNA before sequencing the V3-V4 hypervariable region of the 16S rRNA gene on the Illumina MiSeq system (Illumina, San Diego, CA). Bioinformatic analysis was performed on the Nephele platform using the DADA2 pipeline in R (ClinicalTrials.gov identifier: NCT05757674).

RESULTS: Thirty-three patients (age: 75 ± 7 years, 17 women) and 34 age- and sex-matched controls (age: 73 ± 7 years, 18 women) were analyzed. No differences in height, weight, body mass index, smoking, or systemic comorbidities were noted between the groups. The most prevalent phyla in both groups were Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteria. The most prevalent genus was Bacteroides in both groups. Neither alpha nor beta diversity was different among the groups. The differential abundance analysis using Analysis of Compositions of Microbiomes with Bias Correction 2 (ANCOM-BC2) showed that some Amplicon Sequence Variants (ASVs) from the Coprococcus genus were more abundant in controls than in patients with AMD, whereas several ASVs from Bacteroides were more abundant in the AMD group.

CONCLUSIONS: In our sample, the intestinal microbiome of newly diagnosed patients with neovascular age-related AMD showed some small but noteworthy differences compared to matched healthy controls. Some Bacteroides ASVs were enriched in AMD patients, while certain Coprococcus ASVs were more abundant in controls.},
}

@article {pmid41874061,
year = {2026},
author = {Liu, T and Liao, YF and Liu, JX and Zhang, YP and Yu, YL and Wang, T and Wu, ZX and You, ZP},
title = {Advances in the application of metal-organic frameworks in ophthalmology.},
journal = {Biomaterials science},
volume = {},
number = {},
pages = {},
doi = {10.1039/d5bm01641j},
pmid = {41874061},
issn = {2047-4849},
abstract = {The global burden of vision impairment and blindness caused by eye diseases continues to grow. The eye's inherent physiological barriers-such as the corneal barrier and blood-retinal barrier-lead to challenges in traditional therapies, including low drug bioavailability, poor targeting, and the need for frequent administration. Metal-Organic Frameworks (MOFs), as a class of emerging porous materials, offer promising solutions to overcome these delivery bottlenecks due to their tunable pore structures, high specific surface areas, and ease of functionalization. This review systematically summarizes the latest research advances of MOFs in ophthalmology, focusing on their application as smart carriers for treating various eye diseases including infectious keratitis, bacterial endophthalmitis, glaucoma, age-related macular degeneration, and diabetic retinopathy. It also highlights their innovative use as sensors for tear biomarker detection, intraocular pressure monitoring, and aqueous humor proteomics analysis. Furthermore, this paper delves into ocular delivery strategies for MOFs and systematically analyzes the challenges and future research directions for their clinical translation. It concludes that optimizing material design, strengthening interdisciplinary collaboration, and developing multifunctional integrated platforms are key to advancing this field.},
}

@article {pmid41875412,
year = {2026},
author = {Spaide, RF},
title = {Dry Retina Is Not Enough: Re-centering Visual Acuity in Anti-VEGF Therapy for Neovascular AMD.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000004841},
pmid = {41875412},
issn = {1539-2864},
abstract = {Anti-vascular endothelial growth factor therapy transformed neovascular age-related macular degeneration, but durability and anatomic drying gradually became proxies for efficacy. Visual acuity gains have plateaued across successive agents. Feedback-driven treatment strategies obscure differences. Future progress should be judged by meaningful improvements in visual function, not extended dosing intervals alone.},
}

@article {pmid41866494,
year = {2026},
author = {Bhargava, M and Mehta, KN and Parikh, BH and Liu, Z and Su, X},
title = {Advances in retinal pigment epithelium transplantation for age-related macular degeneration: bridging biology to therapeutic frontiers.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-04971-0},
pmid = {41866494},
issn = {1757-6512},
}

@article {pmid41867320,
year = {2026},
author = {Lin, Z and Huang, L and Li, D and Yi, S and Weng, J},
title = {Case Report: Maculopathy following standard dose intracameral cefuroxime injection during ICL surgery.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1778421},
pmid = {41867320},
issn = {2674-0826},
abstract = {PURPOSE: To describe two rare occurrences of acute toxic maculopathy, specifically Intracameral Cefuroxime Ocular Toxic Syndrome (ICOTS), following uncomplicated posterior-chamber toric phakic implantable collamer lens (TICL) surgery despite the administration of a standard dosage of cefuroxime.

MATERIALS AND METHODS: This case report identified two patients from a clinical volume of 1,590 eyes treated between 2021 and 2024. Inclusion criteria consisted of patients undergoing bilateral TICL implantation with intracameral cefuroxime who presented with unexpected visual disturbances on postoperative day 1. To isolate cefuroxime as the primary toxic factor, exclusion criteria included systemic comorbidities (such as diabetes mellitus), pre-existing ocular pathologies (including uveitis, macular degeneration, or prior retinal detachment), history of prostaglandin analog use, or baseline structural abnormalities on preoperative optical coherence tomography (OCT). Clinical evaluation included UDVA, BCVA, and SD-OCT imaging.

RESULTS: Two female patients (aged 29 and 32) underwent bilateral TICL surgery with 0.1 mL of 10 g/L intracameral cefuroxime administered at the conclusion of the procedure. On postoperative day 1, both patients presented with unilateral vision loss (BCVA 20/32 and 20/80, respectively) and reported dim or distorted vision. SD-OCT revealed macular edema and subretinal fluid (SRF). Following conventional postoperative treatment with topical steroids and nonsteroidal anti-inflammatory drugs, complete absorption of SRF was achieved within two weeks to one month, and BCVA improved to 20/16 and 20/20, respectively.

CONCLUSION: While intracameral cefuroxime is a highly effective prophylactic against endophthalmitis, it may cause sporadic toxic maculopathy even at standard doses during ICL surgery. Unlike typical post-cataract inflammatory edema, ICOTS presents acutely on day 1. Surgeons should maintain a high index of suspicion and utilize early OCT imaging for unexpected postoperative visual disturbances.},
}

@article {pmid41867365,
year = {2025},
author = {Gregory-Evans, K and Gregory-Evans, CY},
title = {Molecular insights into foveal hypoplasia: development, genetics, mechanisms, and models.},
journal = {Molecular vision},
volume = {31},
number = {},
pages = {319-343},
pmid = {41867365},
issn = {1090-0535},
mesh = {Humans ; *Fovea Centralis/abnormalities/pathology/growth & development/metabolism ; Animals ; Disease Models, Animal ; Eye Diseases, Hereditary ; Nystagmus, Congenital ; },
abstract = {The fovea is an anatomic specialization of the human retina critical for high visual acuity, color vision, and contrast sensitivity. The molecular and cellular pathways directing this focal topography are still to be determined. Abnormalities of the fovea (e.g., foveal hypoplasia in children) are considered a significant contributor to reduced quality of life. In addition, the fovea is often damaged in common retinal diseases, such as age-related macular degeneration and diabetic retinopathy, with a global economic burden of $500 billion USD. Currently, there are no treatments for foveal defects. Most genes contributing to foveal abnormalities have been identified but are yet to be characterized and studied. This is because common laboratory animals do not have a fovea, and only rare human tissue samples are available during the major phase of foveal maturation, from birth to the end of the fourth year of life. We discuss validation of the anole lizard, which has a foveal structure, for research studies into foveal development. Since foveal development continues after birth, it may be possible to stimulate new foveal maturation where there is developmental damage. From this review, we propose an evidence-based cellular mechanism that offers new possibilities for testing future therapies for foveal defects.},
}

Humans
*Fovea Centralis/abnormalities/pathology/growth & development/metabolism
Animals
Disease Models, Animal
Eye Diseases, Hereditary
Nystagmus, Congenital

@article {pmid41867749,
year = {2026},
author = {Wu, Y and Tong, Y and Byrnes, KG and Zhou, Q and Dong, C and Benjamin, C and Parker, E and Bao, D and Ren, Z and Anderson, CA and Ufret-Vincenty, RL and He, YG and Zhang, Z and Hinkle, D and Ma, J and Wang, S},
title = {Myofibroblast lineage mapping and inhibiting subretinal fibrosis by targeting SMAD3 and MRTF pathways via microRNA-24 functional study.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.03.03.709397},
pmid = {41867749},
issn = {2692-8205},
abstract = {Subretinal fibrosis underlies the end-stage pathogenesis of retinal diseases including age- related macular degeneration (AMD). It can disrupt retinal structure and eventually lead to legal blindness by generating contractile force, fibrotic scarring, subretinal hemorrhage, and retinal detachment. Myofibroblasts are the predominant cells critically involved in subretinal fibrosis, however, the cellular contribution to myofibroblasts remains unclear. Here we demonstrate that multiple cell lineages, including macrophages, endothelial cells (EC), retinal pigment epithelial (RPE) cells and pericytes, significantly contribute to myofibroblasts in a laser-induced subretinal fibrosis model. We found microRNA miR-24 is significantly downregulated in the plasma of wet AMD patients. Overexpression of miR-24 represses epithelial-mesenchymal transition (EMT), endothelial-mesenchymal transition (EndMT), and the resulting fibrosis by regulating TGF- β/SMAD3 and PAK4/LIMK2/MRTF pathways. Consistently, a combination of SMAD3 and MRTF inhibitors show superior efficacy to individual inhibitors in repressing fibrosis in vitro and laser-induced subretinal fibrosis in vivo . Together, these suggest the contribution of multiple cell-types in myofibroblast transformation in subretinal fibrosis, and repression of miR-24 -regulated TGF-β/SMAD3 and PAK4/LIMK2/MRTF pathways in multiple cell types holds therapeutic potential for treating subretinal fibrosis in AMD and other fibrotic disorders.},
}

@article {pmid41867838,
year = {2026},
author = {Little, DR and Shirinifard, A and Lupo, M and Wu, CH and Chen, H and Clemons, MR and Maclean, M and Marola, OJ and Howell, GR and Li, C and Dyer, MA},
title = {Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.27.708333},
pmid = {41867838},
issn = {2692-8205},
abstract = {Imageomics uses machine learning to accelerate our understanding of biological traits and human disease processes. Some of the earliest imageomics applications used deep learning to assess human diseases. For example, retinal fundus images were analyzed to diagnose diabetic retinopathy. The imaging modality optical coherence tomography (OCT) is widely used to diagnose and monitor the progression of retinopathy in patients and preclinical models. The standardized instrumentation and image format of OCT lends itself to imageomics, but generalizable, automated pipelines for segmentation and quantitation of large numbers of OCT images are still in early development. Here, we present the automated, end-to-end pipeline Crop-OCT that extracts features from thousands of OCT images, while preserving their location within the eye. We used the Crop-OCT pipeline on a diverse dataset, including 13 genetic models of retinopathy, with more than 20,000 OCT images, which allowed us to analyze nearly 6 million measured features. The pipeline was generalized on an independent dataset that was analyzed in a blinded manner. The pipeline enabled us to monitor ocular changes associated with aging and progression of diseases, such as retinitis pigmentosa, Leber congenital amaurosis, achromatopsia, Stargardt disease, diabetic retinopathy, and age-related macular degeneration. We also characterized heterogeneity across animals and identified regional and focal lesions. Our pipeline will unify feature extraction for preclinical models of retinal disease and serve as a foundation for future multimodal data integration for artificial intelligence applications based on imageomics.},
}

@article {pmid41868207,
year = {2026},
author = {Guo, B and Wang, D and Zhao, Z and Liu, W and Hou, J and Liang, R and Zhang, L},
title = {Evaluation of classification performance for six types of fundus diseases in OCT images based on multi-source training strategy.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1775911},
pmid = {41868207},
issn = {2296-858X},
abstract = {OBJECTIVE: Currently, publicly available Optical Coherence Tomography (OCT) datasets are commonly plagued by limited coverage of disease categories, scarce samples and severe class imbalance, which leads to insufficient generalization ability of deep learning models in real-world clinical settings. This study aims to construct a high-quality OCT dataset encompassing six key types of fundus lesions and normal controls, and to systematically evaluate the improvement effect of training strategies for multi-source data fusion on the performance of multi-class classification.

METHODS: We integrated local clinical data from Shanxi Eye Hospital with the latest public dataset OCTDL to establish a combined dataset. This dataset consists of 6,165 images, covering seven categories: age-related macular degeneration (AMD), diabetic macular edema (DME), retinal artery occlusion (RAO), retinal vein occlusion (RVO), epiretinal membrane (ERM), vitreomacular interface disease (VID), and normal controls (NO). On this basis, six representative deep learning architectures were selected, and two training paradigms were compared under unified experimental settings: (1) Training exclusively on open-source OCTDL data (S1); (2) Joint training using both local data and OCTDL data (S2). All models were evaluated on the identical OCTDL test set. A comprehensive analysis was conducted using multi-dimensional metrics including accuracy, weighted F1-score, class-specific recall, and area under the curve (AUC), with a particular focus on the misdiagnosis rate.

RESULTS: The S1 strategy exhibited significantly limited model recognition capability due to the extremely small sample sizes of certain categories. In contrast, the S2 strategy markedly improved the overall performance of the models. Confusion matrix analysis demonstrated that ViT-Base achieved the optimal performance under the S2 strategy: the accuracy reached 93.61%, the misdiagnosis rate of RAO was reduced to 0%, the misdiagnosis rate of AMD was controlled at 1.34%, and the misdiagnosis rate of RVO decreased from 14.89 to 8.51%.

CONCLUSION: Multi-source data fusion serves as an effective approach to enhance the robustness of OCT multi-category classification models, and it can notably strengthen the recognition capability for certain diseases in particular. This study not only verifies the universal benefits of this strategy but also reveals the critical impact of model selection on the transfer learning effect.},
}

@article {pmid41868220,
year = {2026},
author = {Kim, MS and Nam, S and Lee, J and Woo, SJ},
title = {Prevalence, incidence and risk factors of visual disability in patients with exudative age-related macular degeneration: a nationwide population-based study in Korea.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1766076},
pmid = {41868220},
issn = {2296-858X},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss in the elderly. Although anti-vascular endothelial growth factor (VEGF) therapy has improved the visual prognosis of exudative AMD, a considerable proportion of patients still develop severe vision loss. However, real-world data on the prevalence, incidence and risk factors for visual disability among patients with exudative AMD remain limited. This study investigates the prevalence, incidence and risk factors for visual disability among patients with exudative AMD.

METHODS: This nationwide, population-based retrospective cohort study used Korean National Health Insurance Service data from 2009 to 2023. Patients with newly diagnosed exudative AMD were identified, with a two-year washout period (2009-2010). Prevalence, incidence, hazard ratio (HR) for visual disability were analyzed.

RESULTS: A total of 147,406 patients with exudative AMD were included. The prevalence of visual disability in 2023 was 4.82% and the overall incidence rate was 12.18 per 1,000 person-years. At 8 years, the cumulative incidence probability of monocular visual disability was 4.8% (95% CI, 4.6-5.1), and that of binocular visual disability was 4.4% (95% CI, 4.1-4.7). The mean duration from exudative AMD diagnosis to visual disability was 3.3 ± 2.6 years. The risk of visual disability increased with older age group (HR, 1.38; 95% CI, 1.35-1.42) and lower income level (HR, 1.06; 95% CI, 1.05-1.08). Female sex (HR, 1.41; 95% CI, 1.35-1.47), diabetic retinopathy (HR, 1.16; 95% CI, 1.08-1.25), glaucoma (HR, 1.10; 95% CI, 1.05-1.15), and severe intraocular hemorrhage requiring vitrectomy (HR, 3.14; 95% CI, 2.63-3.75) were also significant risk factors. A decreasing trend in visual disability incidence was observed among patients who were more recently diagnosed with exudative AMD (-0.25% point per year; p < 0.001).

CONCLUSION: The burden of AMD-related visual disability remains significant, highlighting the need for strategies to improve treatment adherence and ensure equitable access to vision-preserving care. The decreasing trend of visual disability in recent years suggests the practical benefit of improved access to anti-VEGF treatment through lower drug costs and expanded insurance coverage.},
}

@article {pmid41868245,
year = {2026},
author = {Xu, W and Zhang, J and Shangguan, Y and Luo, R and Zhu, Y and Bi, Y and Chen, L and Li, B},
title = {Targeting the neurovascular unit in retinal fibrosis: mechanisms and therapeutic perspectives.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1776869},
pmid = {41868245},
issn = {2296-858X},
abstract = {Retinal fibrosis, a severe complication observed in conditions like age-related macular degeneration and diabetic retinopathy, characterized by aberrant myofibroblast activation and excessive extracellular matrix (ECM) deposition, which ultimately led to irreversible visual impairment. Currently, the mechanisms underlying retinal fibrosis remain unclear and existing treatments remain incompletely understood. Thus, a comprehensive understanding of disease mechanisms, together with the development of innovative therapeutic approaches, is essential for advancing effective treatment strategies. This review systematically examines the pathogenesis of retinal fibrosis from the perspective of the neurovascular unit (NVU), with a particular focus on the roles of endothelial cells, pericytes, and glial cells in fibrotic processes. It highlights key fibrotic mechanisms, including epithelial mesenchymal transition (EMT) as well as macrophage and pericyte-to-myofibroblast transitions (MMT/PMT). It further analyzes the molecular mechanisms that regulate myofibroblast activation and extracellular matrix deposition. Additionally, this review outlines potential therapeutic targets for the treatment of retinal fibrosis.},
}

@article {pmid41871654,
year = {2026},
author = {Trinh, M and Kalloniatis, M and Jones, BW and Yiu, GC and Borrelli, E and Nivison-Smith, L},
title = {Inner-retinal changes in AMD: Evidence, mechanisms, and future perspectives.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101463},
doi = {10.1016/j.preteyeres.2026.101463},
pmid = {41871654},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) has traditionally been regarded as a disorder of the outer-retina and choroid, characterised by drusen accumulation, retinal pigment epithelium (RPE) dysfunction, and photoreceptor degeneration. However, increasing evidence of inner-retinal involvement across the AMD spectrum, with structural and functional compromise evident from the early stages of disease, challenges this paradigm. Advances in spatially optimised optical coherence tomography (OCT), OCT angiography (OCTA), and high-resolution histology have revealed neuronal, vascular, and glial alterations within the inner-retina that reshape our understanding of AMD pathogenesis. This review synthesises clinical and experimental evidence on inner-retinal changes in AMD, including layer-specific thinning, microvascular rarefaction, impaired neurovascular coupling, and reactive gliosis. Such changes frequently emerge in early AMD, may precede, parallel, or exacerbate outer-retinal degeneration, and are associated with visual dysfunction not fully explained by photoreceptor loss alone. Importantly, mechanistic interactions between inner- and outer-retinal pathology support a bidirectional model of neurodegeneration, wherein region-specific vulnerability is shaped by perfusion dynamics, metabolic demands, and structural connectivity throughout the retina. Recognition of these processes expands the potential for earlier diagnosis, refined monitoring, and novel therapeutic targeting. By integrating structural, functional, and systemic insights, this review reframes AMD as a multi-layer neurovascular disease and underscores the central role of inner-retinal integrity in future AMD research and management.},
}

@article {pmid41864469,
year = {2026},
author = {Leung, HYE and Zhang, J and Radke, NV and Gan, S and Yao, S and Wang, Z and Li, J and Liu, X and Chong, V and Wang, X and Tan, W and Lam, DSC},
title = {Novel drug development for geographic atrophy.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100305},
doi = {10.1016/j.apjo.2026.100305},
pmid = {41864469},
issn = {2162-0989},
abstract = {Geographic atrophy (GA), the advanced stage of dry age-related macular degeneration, has transitioned from an untreatable condition to a field of active therapeutic development. This review outlines the key molecular pathways driving GA progression, including complement system dysregulation, oxidative stress, and chronic inflammation. A marked important therapeutic milestone with the first FDA approvals of complement inhibitors, Pegcetacoplan and Avacincaptad pegol, demonstrated a modest but statistically significant slowing of lesion growth. However, these anatomic benefits have not consistently translated into meaningful functional visual improvement, underscoring the need for additional therapeutic strategies. Beyond complement, the therapeutic landscape is rapidly expanding to include oral agents, topical therapies, implant-based delivery systems, subcutaneous injections, and device-based approaches targeting oxidative stress, neuroprotection, mitochondrial dysfunction, lipid metabolism and proteostasis. Emerging modalities, including gene therapy, stem cell-based repair, and bioelectronic implants, aim to move beyond disease slowing toward durable retinal restoration. Despite progress, significant unmet needs persist. Key challenges include treatment burden associated with frequent intravitreal injections, safety considerations, and the persistent disconnect between anatomic endpoints and functional outcomes. These underscore the necessity for future treatments that not only alter disease anatomy but also effectively preserve patients' vision and improve their quality of life.},
}

@article {pmid41857480,
year = {2026},
author = {Wu, TE and Chen, HS},
title = {Ocular complications from glucagon-like peptide-1 receptor agonists: Clinical evidence, potential mechanisms, and clinical recommendations.},
journal = {Journal of the Chinese Medical Association : JCMA},
volume = {},
number = {},
pages = {},
doi = {10.1097/JCMA.0000000000001370},
pmid = {41857480},
issn = {1728-7731},
abstract = {Glucagon-like peptide-1 receptor agonists (GLP-1 RAs)-central to type 2 diabetes mellitus (T2DM) management owing to their comprehensive benefits (glycemic control, weight reduction, cardiovascular benefits, and renal protection)-exhibit a concerning ocular safety profile. Clinical trial data, notably from SUSTAIN-6, revealed a higher incidence of diabetic retinopathy (DR) complications with semaglutide, particularly in patients with pre-existing DR and rapid HbA1c reduction, reflecting early worsening. Conversely, the REWIND and LEADER trials reported no significant DR, suggesting variability among agents and the potential influence of glycemic trajectory. Observational studies and meta-analyses provide mixed findings: some suggest increased DR progression risk in vulnerable populations, while others indicate a lower risk than insulin therapy. Beyond DR, recent pharmacoepidemiologic studies and pharmacovigilance reports have implicated GLP-1 RAs-especially semaglutide-in nonarteritic anterior ischemic optic neuropathy (NAION), leading the European Medicines Agency to classify NAION as a very rare adverse effect and prompting regulatory scrutiny. Conversely, real-world data suggest possible protective associations with other retinal disorders, including reduced incidence of neovascular age-related macular degeneration and diabetic macular edema, although findings remain inconsistent. The mechanistic pathways involve rapid metabolic shifts, vascular dysregulation, and potentially direct effects on retinal or optic nerve tissue. While GLP-1 RAs confer substantial systemic benefits, their ocular risks appear concentrated in high-risk subgroups. Individualized prescribing, baseline ophthalmic assessment, and interdisciplinary monitoring are essential until ongoing prospective trials clarify their long-term ocular impact.},
}

@article {pmid41858558,
year = {2026},
author = {Tran, MH and Pruitt, K and Bryarly, M and Emordi, I and Ali, A and Ma, L and Fei, B},
title = {Development and validation of a high-resolution hyperspectral imaging system for the retina.},
journal = {Journal of biomedical optics},
volume = {31},
number = {3},
pages = {036006},
pmid = {41858558},
issn = {1560-2281},
mesh = {Animals ; *Hyperspectral Imaging/methods/instrumentation ; Mice ; *Retinal Vessels/diagnostic imaging ; Algorithms ; Phantoms, Imaging ; *Retina/diagnostic imaging ; *Image Processing, Computer-Assisted/methods ; Oxygen/metabolism ; Deep Learning ; Mice, Inbred C57BL ; },
abstract = {SIGNIFICANCE: Early detection of Alzheimer's diseases, diabetic retinopathy, or macular degeneration with advanced retinal imaging technologies can help improve patient care and treatment outcome.

AIM: We aim to create a high-resolution hyperspectral imaging (HSI) system for the retina. Retinal vessel diameter and oxygenation rate will be extracted simultaneously from HSI data.

APPROACH: Our hyperspectral retinal imaging system consists of a snapshot hyperspectral camera, a high-resolution RGB camera, a beamsplitter, and an imaging endoscope. Multiple pansharpening algorithms, including deep learning methods, were developed to generate high-resolution hyperspectral images that were further used for the measurement of vessel size and oxygenation rate in mice.

RESULTS: The hyperspectral retinal imaging system was tested for its spatial resolution and spectral fidelity in retina phantoms. In vivo imaging experiments were performed in mice. The deep learning-based pansharpening algorithm achieved a root mean square error (RMSE) of 2.15 ± 0.64 , a correlation coefficient (CC) of 0.96 ± 0.05 , a spectral angle score of 0.06 ± 0.03 radians, and an error relative global dimensionless synthesis (ERGAS) score of 2.37 ± 1.71 . Oxygen saturation (sO 2) and lumen diameters of blood vessels were measured in the retina. The average lumen diameter of the venules was 45.7 ± 13.6    μ m , whereas the average lumen diameter of the arterioles was 31.5 ± 8.7    μ m . The average arteriole sO 2 was 98%, whereas the average venule sO 2 was 58%.

CONCLUSIONS: A high-resolution hyperspectral imaging system was developed and validated for retina imaging and measurement of blood vessels and oxygen saturation.},
}

Animals
*Hyperspectral Imaging/methods/instrumentation
Mice
*Retinal Vessels/diagnostic imaging
Algorithms
Phantoms, Imaging
*Retina/diagnostic imaging
*Image Processing, Computer-Assisted/methods
Oxygen/metabolism
Deep Learning
Mice, Inbred C57BL

@article {pmid41858680,
year = {2026},
author = {Prasad, M and Nagarkar, A and Agron, E and Weber, C and Chew, EY and De Silva, T and Mukherjee, S},
title = {A Datasheet for the Age-Related Eye Disease Study (AREDS) on the database of Genotypes and Phenotypes.},
journal = {Ophthalmology science},
volume = {6},
number = {4},
pages = {101115},
pmid = {41858680},
issn = {2666-9145},
abstract = {OBJECTIVE: Over the years, the Age-Related Eye Disease Study (AREDS) has contributed to the natural history and understanding of progression related to age-related macular degeneration (AMD) and cataracts. This paper summarizes AREDS data elements available for research.

DESIGN: Data set description for data acquired during AREDS.

PARTICIPANTS: Adults aged 55 to 80 years with no to advanced AMD in 1 eye but visual acuity >20/32 in eye without advanced AMD.

METHODS: database of Genotypes and Phenotypes archives and distributes data acquired in clinical studies such as AREDS. This article provides a detailed description of the data available under controlled access under the National Institutes of Health genomic data sharing Policy.

MAIN OUTCOME MEASURES: Age-Related Eye Disease Study evaluated progression to advanced AMD, 15-letter decrease in visual acuity, and progression of lens opacities as primary outcome measures.

RESULTS: The data set includes 4757 participants enrolled across 11 participating clinical centers representing varying AMD severity categories and lens opacities. The participants' demographics and clinical variables were collected during baseline and follow-up visits, and data elements included ophthalmic images (fundus and lens photographs) with reading center gradings; nutritional estimates captured from food frequency questionnaires; data related to quality of life, hospitalization, morbidity, and mortality; and genetic data (available in a subset of approximately 2400 participants who submitted blood samples).

CONCLUSIONS: Summary of data available under controlled access acquired as part of AREDS was provided. The AREDS data set offers a valuable resource for advancing our understanding of AMD and cataract progression and for developing novel tools and applications to transform ophthalmic diagnostics and therapeutics.

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

@article {pmid41858838,
year = {2026},
author = {Cheng, SY and Giguere, D and Kim, S and Seddon, JM and Caiazzi, J and Gross, K and McHugh, N and Echeverria, D and Alterman, JF and Gray-Edwards, H and Benatti, HR and Renner, L and Woolard, H and Stoddard, J and McGill, TJ and Neuringer, M and Brush, RS and Agbaga, MP and Khvorova, A and Punzo, C},
title = {An siRNA targeting S6k1 identifies photoreceptor phospholipid metabolism as a contributor to lipid buildup in age-related macular degeneration.},
journal = {Molecular therapy. Nucleic acids},
volume = {37},
number = {2},
pages = {102878},
pmid = {41858838},
issn = {2162-2531},
abstract = {Age-related macular degeneration (AMD) remains a leading cause for visual impairment in the elderly. We recently showed that activated mammalian target of rapamycin complex 1 (mTORC1) in photoreceptor cells causes AMD-like pathologies in mouse. Employing mouse genetics, we dissect the mTORC1 pathway and identify ribosomal protein S6 kinase beta-1 (S6k1) as a key component required for disease onset in our mouse model. Using a previously identified fully chemically modified tetravalent small interefing RNA (siRNA) that enriches in photoreceptors, we target S6k1 in mouse, pigs, and non-human primates (NHP) by intravitreal injection. We find that S6k1 silencing in diseased mice reverses phospholipid changes induced by activated mTORC1, restores lysosomal activity of retinal-pigmented epithelium cells, and reduces lipoprotein buildup at Bruch's membrane (BM). In pigs, which do not develop disease, we find a similar shift in phospholipids as in mouse, indicating a conserved role for S6k1 in photoreceptor phospholipid metabolism. In aged NHPs with macular drusen, the lipoprotein-rich BM deposits that are a hallmark of human AMD, S6k1 silencing slows drusen growth over a 6-month period. These findings establish S6k1 as modifier of lipoprotein buildup at the BM and support our siRNA platform as a potential treatment modality for AMD and other retinal diseases.},
}

@article {pmid41860312,
year = {2026},
author = {Khan, A and Hormel, TT and Gao, M and Guo, Y and Zang, P and Wang, J and Hwang, TS and Bailey, ST and Jia, Y},
title = {Automated Segmentation and Characterization of Retinal Hyperreflective Foci in Age-Related Macular Degeneration.},
journal = {Translational vision science & technology},
volume = {15},
number = {3},
pages = {20},
doi = {10.1167/tvst.15.3.20},
pmid = {41860312},
issn = {2164-2591},
mesh = {Humans ; *Tomography, Optical Coherence/methods ; Cross-Sectional Studies ; *Macular Degeneration/diagnostic imaging/diagnosis ; Aged ; Female ; Male ; Neural Networks, Computer ; *Retina/diagnostic imaging/pathology ; Aged, 80 and over ; ROC Curve ; Middle Aged ; },
abstract = {PURPOSE: Retinal hyperreflective foci (HRF) are associated with higher risk of progression to advanced age-related macular degeneration (AMD). To enable automated detection, we developed Foci-Net, a convolutional neural network for segmenting HRF in optical coherence tomography (OCT) volumes.

METHODS: This cross-sectional study included eyes clinically diagnosed with intermediate to advanced AMD and healthy controls. We acquired 6 × 6-mm macular-centered scans using 2 OCT systems. Foci-Net modifies the U-Net by replacing the bottleneck with a fine-to-coarse feature extraction block to improve segmentation of both small and large foci. HRF volume was quantified as the proportion of total volume within each retinal layer and characterized by anatomic location. Model performance was evaluated at the count, pixel, eye, and B-scan levels using F1-score, area under the curve (AUC) of the receiver operating characteristic (ROC) curve, precision, sensitivity, and specificity.

RESULTS: Sixty-one volumetric OCT scans (50 AMD and 11 healthy control eyes) obtained from 50 participants, age 77.65 ± 9.24 years (mean ± SD), of whom 72% were women. Foci-Net achieved F1-scores of 73.0 ± 3.8% counts (based on en face analysis) and 71.6 ± 29.1% pixels (based on cross-sectional analysis) level relative to the ground truth in 3-fold cross-validation. Diagnostic performance was strong, with an AUC of 100 ± 0.0% (eye) and 92.7 ± 0.3% (B-scan) level. HRF was least (2.10%) abundant in the ganglion cell complex and most (55.37%) in the outer nuclear layer.

CONCLUSIONS: A deep learning approach enables fast HRF segmentation, supporting its role as a biomarker for predicting AMD progression.

TRANSLATIONAL RELEVANCE: The proposed HRF segmentation method could enhance AMD diagnosis and prognosis.},
}

Humans
*Tomography, Optical Coherence/methods
Cross-Sectional Studies
*Macular Degeneration/diagnostic imaging/diagnosis
Aged
Female
Male
Neural Networks, Computer
*Retina/diagnostic imaging/pathology
Aged, 80 and over
ROC Curve
Middle Aged