@article {pmid42745211,
year = {2026},
author = {Bora, RA and Aher, P and Magdum, RA and Jagdish, R},
title = {Low Vision Intervention in Individuals with Age-related Macular Degeneration.},
journal = {Annals of African medicine},
volume = {25},
number = {6},
pages = {1400-1404},
doi = {10.4103/aam.aam_329_25},
pmid = {42745211},
issn = {0975-5764},
mesh = {Humans ; *Visual Acuity/physiology ; Female ; *Quality of Life ; *Macular Degeneration/rehabilitation/complications ; Aged ; Prospective Studies ; Male ; *Vision, Low/rehabilitation/etiology ; Activities of Daily Living ; Treatment Outcome ; Middle Aged ; Aged, 80 and over ; Surveys and Questionnaires ; Contrast Sensitivity ; Reading ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Low vision interventions (LVIs) aim to enhance residual visual function and promote independence. This study aimed to evaluate the clinical and functional outcomes of structured LVIs on visual performance, daily functioning, and quality of life in individuals with AMD.

METHODS: A prospective interventional study was conducted over 1 year at Dr. D. Y. Patil Medical College, Hospital, and Research Centre in Pune. Eighty-four participants with confirmed AMD and low vision were enrolled and assessed at baseline, 3 months, and 6 months postintervention. The rehabilitation program included optical, nonoptical, and electronic assistive devices, along with specialized visual training. Primary outcomes included best corrected visual acuity (BCVA), contrast sensitivity, and reading speed. Secondary outcomes were assessed using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) and the modified Barthel index, evaluating self-reported visual function and independence in daily activities.

RESULTS: Of the 84 participants, 78 completed the full follow-up. Statistically significant improvements were observed in BCVA (mean gain: 0.17 logMAR), reading speed (mean increase: 18.8 words/min), and contrast sensitivity (mean gain: 0.22 units). The NEI VFQ-25 composite score improved by an average of 17.3 points, with marked enhancement in near-vision tasks and social engagement. Functional ability, as measured by the Modified Barthel Index, also showed meaningful improvement. No device-related complications were reported, and more than 85% of participants adhered to their prescribed rehabilitation plans.

CONCLUSIONS: Structured low vision rehabilitation leads to significant improvements in visual performance, functional independence, and perceived quality of life among patients with AMD. These findings support the integration of LVIs into standard ophthalmic care protocols for elderly individuals with low vision.},
}

Humans
*Visual Acuity/physiology
Female
*Quality of Life
*Macular Degeneration/rehabilitation/complications
Aged
Prospective Studies
Male
*Vision, Low/rehabilitation/etiology
Activities of Daily Living
Treatment Outcome
Middle Aged
Aged, 80 and over
Surveys and Questionnaires
Contrast Sensitivity
Reading

@article {pmid42745735,
year = {2026},
author = {Samanta, A and Krambeer, C and Flowers, A and Porter, M},
title = {Selective laser trabeculoplasty for anti-VEGF associated intraocular pressure elevation in steroid-naïve eyes.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1675048},
pmid = {42745735},
issn = {2674-0826},
abstract = {PURPOSE: Selective Laser Trabeculoplasty (SLT) is utilized in cases of primary and certain secondary open-angle glaucoma to decrease intraocular pressure (IOP). SLT effectiveness has been demonstrated in patients with increased IOP secondary to intraocular steroids. In addition to intravitreal steroids, intravitreal anti-vascular endothelial growth factor (VEGF) injections are commonly used in patients with diabetic retinopathy and age-related macular degeneration. Some patients receiving anti-VEGF injections experience increases in IOP. No studies have evaluated the effectiveness of SLT for anti-VEGF-associated glaucoma.

METHODS: This was a retrospective, single-center study. Anti-VEGF-associated IOP increase was defined as an eye receiving at least one anti-VEGF intravitreal injection prior to SLT. IOP and the number of pressure-lowering drops were measured at 3-, 6-, 9-, and 12-month post-SLT follow-up appointments. Outcomes included changes in IOP, and the number of IOP-lowering drops prescribed.

RESULTS: Twenty-three eyes from 18 patients were included in this study. The IOP was 18.26 ± 3.33 with 2.6 ± 1. drops prescribed at baseline. Two eyes required repeat SLT. Over the study period, IOP was reduced by 3 to 4.5 mm Hg, with all p-values <0.001. Eight eyes in the study were drop-naïve (no IOP-lowering drops prescribed prior to SLT). Of these, 6/8 (75%) remained drop-free at the end of the observation period. At their final clinic visit, 78.3% of patients were controlled on SLT without further surgical or medical intervention.

CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate the long-term effectiveness of SLT in anti-VEGF-associated open-angle glaucoma in steroid-naïve eyes.},
}

@article {pmid42745817,
year = {2026},
author = {Dutta, AK and Aljarallah, NA and Wahab Sait, AR},
title = {VG-RETFound: a hybrid retinal AI framework for early vision impairment screening through vessel-graph learning and cross-modal fusion.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1905129},
pmid = {42745817},
issn = {2296-858X},
abstract = {INTRODUCTION: Vision impairment caused by retinal diseases stands out as one of the significant sources of irreversible blindness, highlighting the importance of developing robust automated screening tools to detect eye diseases at an early stage. Despite the promising results of recent deep learning approaches to the automatic classification of retinal images, most existing solutions focus on image-based representations and do not consider the importance of vascular topology. To overcome the limitations, this study proposes VG-RETFound - a hybrid framework based on a retinal foundation model and graph-based vascular-topology modeling that can be used to classify multiple retinal categories and detect vision impairment.

METHODS: The authors use RETFound-a retinal foundation model-pretrained on a vast number of retinal images, as well as the Graph Attention Network (GAT), to learn vascular topology features by representing retinal vessels as graphs. The presented approach employs a cross-modal multi-head attention fusion method to integrate features from both modalities in real time. To evaluate the efficiency of VG-RETFound, experiments were conducted using the RFMiD and ODIR-5 K datasets for model training and testing across six retinal categories: Normal, Diabetic Retinopathy, Pathological Myopia, Age-related Macular Degeneration, Hypertensive Retinopathy, and Other Retinal Diseases.

RESULTS: The accuracy of 96.39%, F1-score of 95.84%, MCC of 94.87%, and Kappa of 94.71% were attained on an internal test dataset, while cross-dataset external validation on the BRSET dataset revealed accuracy of 94.81%, F1-score of 94.25%, MCC of 93.09%, and Kappa of 92.94%.

DISCUSSION: These findings demonstrate that integrating retinal foundation models with anatomically informed vessel-topology learning significantly improves classification accuracy, interpretability, and generalization, highlighting the potential of VG-RETFound as a tool for large-scale vision impairment. screening and retinal disease diagnosis.},
}

@article {pmid42745920,
year = {2026},
author = {Liu, X and Liu, H and Wang, L and Zhao, J and Xie, X and Jiang, L and Zhao, CA},
title = {Preclinical evaluation of AL-001, a gene therapy for wet age-related macular degeneration.},
journal = {Frontiers in genetics},
volume = {17},
number = {},
pages = {1836684},
pmid = {42745920},
issn = {1664-8021},
abstract = {BACKGROUND: Frequent intravitreal administration of antivascular endothelial growth factor Vascular endothelial growth factor agents remains a major limitation in the management of wet age-related macular degeneration (wAMD). This study evaluated whether suprachoroidal delivery of an engineered recombinant adeno-associated viral (rAAV)-aflibercept vector could achieve sustained, targeted expression with improved efficacy and safety compared with intravitreal administration.

METHODS: AL-001, an engineered rAAV vector expressing aflibercept, was developed and characterized. Its expression profile was first assessed in New Zealand white rabbits following suprachoroidal space (SCS) injection. Efficacy, pharmacokinetics, and safety were then evaluated in a nonhuman primate model of laser-induced choroidal neovascularization (CNV), comparing SCS and intravitreal (IVT) administration routes.

RESULTS: AL-001 efficiently expressed aflibercept in relevant ocular cells in vitro. In rabbits, SCS administration produced sustained aflibercept levels in ocular tissues. In the nonhuman primate CNV model, a single SCS injection of AL-001 showed favorable efficacy to IVT injection and a notable mild inflammatory response. At week 4, grade IV lesion incidence was 0% (0/48) after SCS administration versus 14.3% (6/42) after IVT administration (absolute difference, -14.3 percentage points; 95% CI, 3.7%-27.8%; P = 0.0258). Throughout follow-up, mean leakage area and grade IV lesion incidence remained 0 with SCS, versus IVT peaks of approximately 0.3 mm[2] and 33.0%, respectively, declining to 0.03 mm[2] and 2.0% by day 100. Both the medium and high doses decreased pathological vascular leakage and subretinal hyperreflective material. Vector administration preceded laser-induced CNV modeling, demonstrating that sustained intraocular aflibercept expression in the retina and choroid provided durable antiangiogenic protection. Pharmacokinetic analysis confirmed distinct ocular exposure profiles between routes, with viral genomes confined predominantly to the injected eye and no significant systemic accumulation. AL-001 was well tolerated, without sustained intraocular pressure elevation or severe ocular inflammation, and only mild-to-moderate treatment-emergent adverse events. Low pre-existing anti-AAV2 immunity and time-dependent neutralizing antibody responses postdosing, informing a translational model for patient stratification and redosing feasibility.

CONCLUSION: Suprachoroidal administration of AL-001 is well tolerated and provides durable, targeted aflibercept expression with pronounced antiangiogenic efficacy. These results support AL-001 as a promising, long-acting therapeutic candidate for wAMD.},
}

@article {pmid42746219,
year = {2026},
author = {Samaiya, PK and Agrawal, A and Kesharwani, S and Sathe, R and Prajapati, SK and Majumdar, S},
title = {Microbiota-mitochondria axis in neurodegenerative disorders and retinal dysfunction: mechanisms and emerging therapeutic opportunities.},
journal = {Frontiers in pharmacology},
volume = {17},
number = {},
pages = {1889898},
pmid = {42746219},
issn = {1663-9812},
abstract = {The gut microbiota crucial role in maintaining host metabolism, immune homeostasis, intestinal integrity, and mitochondrial function. Emerging evidence suggests that dysregulation of the microbiota-mitochondria axis represents one of the key mechanisms linking gut dysbiosis to the development of neurodegenerative and ocular diseases. The dysbiosis causes disruptions in mitochondrial physiology due to lower levels of short-chain fatty acids, increased intestinal permeability, endotoxemia, oxidative stress, and inflammation. These mechanisms contribute to the pathogenesis of Alzheimer's disease, Parkinson's disease, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, and central serous chorioretinopathy. Environmental factors such as unhealthy dietary patterns, excessive antibiotic use, and prolonged exposure to artificial blue light may exacerbate dysbiosis and further disrupt mitochondrial homeostasis, thereby contributing to disease progression. We also elaborated the emerging therapeutic strategies targeting both the gut microbiota and mitochondrial function, including next-generation probiotics, postbiotics, dietary interventions, mitochondria-targeted antioxidants, NAD[+] precursors, and precision medicine approaches. Collectively, current evidence represents the microbiota-mitochondria axis as a one of the promising mechanistic and therapeutic targets for neurodegenerative and ocular diseases. However, most therapeutic evidence discussed in this review is derived from preclinical studies, with relatively limited clinical validation. Future well-designed longitudinal studies and randomized clinical trials are essential to establish efficacy, safety, and translational applicability in humans.},
}

@article {pmid42746273,
year = {2026},
author = {Chou, Z and Saade, C},
title = {Bilateral Choroidal Neovascular Membranes in a Patient With a C1QTNF5 Mutation Managed With Long-Term Anti-VEGF Therapy and PRN Protocol: A Case Report.},
journal = {Case reports in ophthalmological medicine},
volume = {2026},
number = {},
pages = {6047720},
pmid = {42746273},
issn = {2090-6722},
abstract = {Choroidal neovascular membranes (CNVM) are abnormal vascular complexes that can cause serious visual morbidity if untreated. They can be induced by the C1QTNF5 mutation, which disrupts retinal pigment epithelium (RPE) adhesion and leads to progressive sub-RPE deposit accumulation. Due to its overlapping clinical presentation with age-related macular degeneration (AMD), C1QTNF5-associated CNVM is often misdiagnosed. Early recognition of atypical CNVM clinical presentations is essential to prompt genetic testing and initiate personalized antivascular endothelial growth factor (anti-VEGF) therapy. We report a 57-year-old male with a history of pontine stroke and strabismus surgery who presented with bilateral submacular hemorrhages and visual distortion. Given the atypical bilateral presentation and absence of drusen, genetic testing was performed. A pathogenic C1QTNF5 mutation with a p. Asn22Lys variant was identified. Treatment was initiated with intravitreal bevacizumab (IVA) injection and switched to aflibercept (IVE). After 2 years of tailored injection intervals based on optical coherence tomography (OCT) and visual acuity, the patient achieved visual acuity of 20/25 in both eyes with complete or near-complete resolution of subretinal fluid. A pro re nata (PRN) protocol was then initiated, and vision remained stable at the 4-year follow-up. This case highlights the importance of considering inherited retinal disease in atypical CNVM presentations. Early diagnosis, genetic testing, and individualized, imaging-driven anti-VEGF therapy can lead to long-term stability and favorable visual outcomes in patients with C1QTNF5-associated CNVM. Although causality cannot be established from a single case, concurrent glaucoma findings support the need for comprehensive ocular surveillance in patients with C1QTNF5 mutations.},
}

@article {pmid42740461,
year = {2026},
author = {Ørskov, M and Cehofski, LJ and Faber, C and Forte, P and Hansen, MS and Muttuvelu, DV and Niazi, S and Schou, MG and Shekho, N and Reiter, GS and Utheim, TP and Vergmann, AS and Subhi, Y},
title = {Accelerated biological ageing is associated with a large drusen burden.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70237},
pmid = {42740461},
issn = {1755-3768},
abstract = {PURPOSE: To investigate the association between accelerated biological ageing, measured by Phenotypic Age (PhenoAge) and PhenoAge Acceleration (PhenoAgeAccel), and features of early and intermediate age-related macular degeneration (AMD) in a population-based cohort.

METHODS: This cross-sectional study used data from the National Health and Nutrition Examination Survey. Biological age was estimated using the PhenoAge algorithm, a composite of routine blood biomarkers and chronological age, and PhenoAgeAccel was defined as the residual from regression of PhenoAge on chronological age. Retinal outcomes were drusen ≥500 μm (primary outcome), drusen ≥125 μm and pigmentary abnormalities. Associations were evaluated using logistic regression adjusted for biological sex, race/ethnicity, smoking, body mass index and diabetes.

RESULTS: A total of 5322 participants were included (mean age 59.4 ± 12.4 years; 50.4% female). Drusen ≥500 μm were present in 4.1%, drusen ≥125 μm in 10.2% and pigmentary abnormalities in 5.6%. PhenoAgeAccel > + 3 years was associated with higher odds of drusen ≥500 μm (OR: 1.56, 95%CI: 1.07-2.27, p = 0.022), whereas no association was observed for <-3 years. Each 1-year increase in PhenoAgeAccel was associated with higher odds of drusen ≥500 μm (OR: 1.02, 95%CI: 1.00-1.04, p = 0.022). PhenoAgeAccel > + 3 years was also associated with drusen ≥125 μm (OR: 1.29, 95%CI: 1.00-1.65, p = 0.049), but not with pigmentary abnormalities.

CONCLUSION: Accelerated biological ageing was associated with increased drusen burden, but not pigmentary abnormalities, suggesting that early structural features of AMD may reflect broader systemic ageing processes.},
}

@article {pmid42741500,
year = {2026},
author = {Cui, X and Zhao, Q and Hui, J and Han, Z and Yu-Wai-Man, P and Han, Q},
title = {Decoding the Bone-Eye Axis: Machine Learning for Age-Related Macular Degeneration Risk Prediction.},
journal = {Cyborg and bionic systems (Washington, D.C.)},
volume = {7},
number = {},
pages = {0676},
pmid = {42741500},
issn = {2692-7632},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss, yet systemic determinants of its risk remain incompletely understood. Bone mineral density (BMD), a marker of skeletal and biological aging, may reflect shared pathways linking systemic and retinal degeneration. We investigated the association between BMD and AMD using a multilayered framework integrating epidemiological analyses, Mendelian randomization (MR), proteomic and metabolomic profiling, machine learning, and an experimental low-BMD model. Across 3 cohorts, including UK Biobank, National Health and Nutrition Examination Survey, and a hospital-based Tianjin cohort, lower BMD was consistently associated with higher AMD risk, although AMD ascertainment and BMD measurement differed across cohorts. Two-sample MR analyses provided supportive genetic evidence consistent with a modest potential contribution of higher BMD to lower AMD risk, while sensitivity analyses did not indicate strong evidence of reverse causality. Machine learning models identified BMD as a recurrent predictive contributor alongside age, but its incremental clinical utility requires formal evaluation using models with and without BMD. UK Biobank proteomic and metabolomic analyses revealed overlapping molecular signatures involving extracellular matrix remodeling, lipid transport, amino acid metabolism, and inflammatory pathways. Two-step MR prioritized circulating proteins including granzyme A, collagen type II alpha 1 chain, and NEL-like protein 1 as candidate molecular intermediates rather than established mechanistic mediators. In a glucocorticoid-induced low-BMD rat model, retinal alterations relevant to degeneration, including outer retinal thinning, vascular narrowing, and delayed visual-spatial performance, were observed, but these findings should not be interpreted as direct validation of AMD pathology. Overall, these findings support an association between lower BMD and AMD risk and suggest that BMD may act as an accessible marker of systemic aging processes related to retinal vulnerability.},
}

@article {pmid42741679,
year = {2026},
author = {Kang, J and Park, K and Choi, S and Han, S and Hwang, BE and Lee, JH and Jang, M and Chung, EK and Cho, H and Heo, Y and Han, S},
title = {Phase I Randomized Study of SCAI-005 Ophthalmic Solution: Safety, Tolerability, and Pharmacokinetics in Healthy Korean Adults.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101358},
pmid = {42741679},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate the safety, tolerability, and pharmacokinetic (PK) profiles of SCAI-005-a topical ophthalmic solution of axitinib for neovascular age-related macular degeneration (AMD), a VEGF receptor tyrosine kinase inhibitor-following single and multiple ascending doses (SAD and MAD) in healthy Korean adults.

DESIGN: Randomized, double-masked, placebo-controlled, single- and multiple-ascending-dose phase I study.

SUBJECTS: Forty-eight healthy Korean adults were randomized 3:1 (active:placebo) into six cohorts across SAD (0.04% as a single drop, 0.08% as a single drop, and 0.08% as two drops) and MAD (0.04% 1 drop three times daily (TID), 0.08% 1-drop TID, and 0.08% two-drop TID for 7 days) groups.

METHODS: SCAI-005 or placebo was administered topically to 1 eye per subject. Serial blood samples were collected for systemic PK analysis using noncompartmental analysis. Safety was assessed through treatment-emergent adverse events (TEAEs), ophthalmic examinations, vital signs, electrocardiography, and clinical laboratory tests.

MAIN OUTCOME MEASURES: Primary outcomes were safety and tolerability. Secondary outcomes included systemic PK parameters (Cmax and AUClast) and dose proportionality.

RESULTS: Forty-seven of 48 subjects (97.9%) completed the study. TEAEs were reported in 7 subjects (14.6%), with no obvious dose-dependent trend in this small sample. All treatment-related TEAEs were grade 1 in severity. No clinically significant changes were observed in ophthalmic assessments. SCAI-005 was rapidly absorbed following topical administration, with day 8 postdose peak systemic concentrations (Cmax) approximately 66- to 282-fold lower than the reported steady-state Cmax for oral axitinib 5 mg twice daily. Because predose trough concentrations were below the assay limit in most subjects, formal steady state could not be confirmed; repeated-dose parameters are therefore reported as day 8 postdose descriptive PK parameters. In the dose proportionality analysis, Cmax findings were broadly consistent with dose proportionality in both SAD and MAD cohorts. AUClast slope estimates were above unity in both cohorts (1.64-1.69) with confidence intervals not including unity.

CONCLUSIONS: Topical SCAI-005 was generally well tolerated in this small first-in-human study in healthy Korean adults, producing low systemic axitinib exposure and no obvious short-term safety signal. These findings will require confirmation in phase II studies enrolling the target neovascular AMD population.

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

@article {pmid42742484,
year = {2026},
author = {Li, Y and Xiao, F and Liu, Z and Zhang, Y and Yu, J and Chen, Y and Pan, H and Xu, N and Sheng, F and Han, H and Fu, Q and Zhang, S and Gao, J and Tao, W and Yao, K and Kong, N},
title = {Cornea-Penetrating Nanodrug Co-Delivering VEGF-Silencing siRNA and Lutein for Treating Age-Related Macular Degeneration.},
journal = {Advanced materials (Deerfield Beach, Fla.)},
volume = {},
number = {},
pages = {e74994},
doi = {10.1002/adma.74994},
pmid = {42742484},
issn = {1521-4095},
support = {52503205//National Natural Science Foundation of China/ ; 82572387//National Natural Science Foundation of China/ ; U24A20705//Regional Innovation Development Joint Fund of the National Natural Science Foundation of China/ ; 2024ZY01057//Central Guidance for Local Scientific and Technological Development Funding Program/ ; LQN25B020004//Zhejiang Provincial Natural Science Foundation of China/ ; },
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly, driven by oxidative stress, chronic inflammation, and pathological choroidal neovascularization (CNV). Although intravitreal anti-vascular endothelial growth factor (VEGF) therapies remain the current clinical standard, their invasive nature and requirement for long-term repeated injections present substantial risks and patient burden, underscoring an urgent need for noninvasive therapeutic alternatives. Here, we develop a noninvasive, cornea-penetrating nanodrug based on chitosan-modified lipid-polymer hybrid nanoparticles (LPNPs) for co-delivery of lutein and VEGF-silencing siRNA (Chi@Lu/si NPs) to treat AMD. The structurally stabilized nanoparticles overcome the intrinsic instability of siRNA and the poor solubility of lutein, while the chitosan coating confers strong mucoadhesion and transient modulation of epithelial tight junctions, enabling a 3.3-fold enhancement in trans-epithelial transport across the ocular surface. Once delivered to the posterior segment, lutein effectively scavenges excessive reactive oxygen species and suppresses inflammatory cascades, whereas siRNA-VEGF achieves precise VEGF gene silencing, collectively interrupting the pathological cycle driving CNV progression. In a laser-induced CNV mouse model, topical administration of Chi@Lu/si NPs twice daily exerted potent inhibitory effects on neovascularization, with therapeutic efficacy comparable to that of intravitreal bevacizumab, reducing CNV lesion thickness to 58.9% of pre-treatment levels while maintaining excellent ocular biocompatibility.},
}

@article {pmid42743220,
year = {2026},
author = {Lo, C and Jackson, ML},
title = {Clinical characteristics and microperimetry of patients with myopic maculopathy referred to vision rehabilitation compared to age related macular degeneration.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0356824},
pmid = {42743220},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/rehabilitation/physiopathology/diagnosis/complications ; Female ; Aged ; Male ; Retrospective Studies ; Aged, 80 and over ; Visual Acuity ; Visual Field Tests ; Middle Aged ; *Myopia/rehabilitation/physiopathology/complications ; },
abstract = {Myopic maculopathy (MM) is a progressive degenerative change of the retina and choroid associated with high myopia leading to central vision loss. The burden of MM is anticipated to increase due to the rising prevalence of myopia globally. Patients with MM are often referred for vision rehabilitation (VR) to help adapt to visual impairment. VR aims to allow patients to continue performing tasks and remain safe despite vision loss, typically through training with optical devices, assistive technology, or new strategies. This study compares the presenting clinical characteristics and VR process of patients with MM to patients with age-related macular degeneration (AMD), the latter being the most common diagnosis of patients referred for VR. This retrospective chart review included 32 consecutive patients with MM and 32 randomly selected patients with AMD referred for VR. Only patients with visual acuity in either eye better than 20/200 were included to represent the early stage of both disease processes. Available microperimetry data were collected for all eyes with a visual acuity better than 20/200 and graded for the presence of scotomas by two independent reviewers. Patients with MM were significantly younger (p < 0.0001) than those with AMD (mean age 68.0 vs 81.6 years respectively). Reported priority goals for vision rehabilitation showed a significant trend: patients with MM and moderate acuity prioritized daily living tasks more frequently (67%, p = 0.0045) than patients with AMD. At good acuity (>20/50), dense paracentral scotomas trended towards being more prevalent amongst patients with MM compared to moderate acuity (between 20/50 and 20/200) where central scotomas were more prevalent amongst patients with AMD. Patients with early MM have unique characteristics at presentation for VR compared to patients with AMD. It is important for providers to be aware of the visual challenges faced by younger patients with paracentral scotomas, which may warrant VR referral even when visual acuity is good.},
}

Humans
*Macular Degeneration/rehabilitation/physiopathology/diagnosis/complications
Female
Aged
Male
Retrospective Studies
Aged, 80 and over
Visual Acuity
Visual Field Tests
Middle Aged
*Myopia/rehabilitation/physiopathology/complications

@article {pmid42743257,
year = {2026},
author = {Park, D and Oh, R and Baek, J and Bae, K},
title = {Evaluating an AI-assisted triage workflow for retinal diseases.},
journal = {PLOS digital health},
volume = {5},
number = {9},
pages = {e0001700},
pmid = {42743257},
issn = {2767-3170},
abstract = {The clinical value of artificial intelligence (AI) in fundus photography depends on workflow efficiency as well as diagnostic performance. We evaluated an AI-assisted negative-screening workflow for diabetic retinopathy (DR), retinal vein occlusion (RVO), and age-related macular degeneration (AMD) using 6,904 color fundus photographs independently graded by three retina specialists. In this workflow, AI-negative images were classified as negative without ophthalmologist review, whereas AI-positive images were referred for human interpretation. For each reader-disease pair, the reference standard was agreement between the other two readers; discordant cases were excluded (DR, 1.2%-2.3%; RVO, 0.3%-0.6%; AMD, 6.1%-11.6%). The workflow reduced direct ophthalmologist review to 7.3%-8.0% of images for DR, 11.7%-11.9% for RVO, and 13.5%-16.8% for AMD. For DR, sensitivity decreased significantly (0.9168 to 0.8838; difference, -0.0330; 95% confidence interval [CI], -0.0495 to -0.0165; p < 0.001), whereas specificity did not change significantly (0.9961 to 0.9983; p = 0.183). For RVO, sensitivity was unchanged (0.9807) and specificity did not change significantly (0.9985 to 0.9988; p = 0.320). For AMD, sensitivity decreased significantly (0.8570 to 0.8445; difference, -0.0124; 95% CI, -0.0215 to -0.0033; p = 0.008), whereas specificity did not change significantly (0.9685 to 0.9843; p = 0.324). In an exploratory image-level analysis for at least one target disease, review decreased to 27.7%-30.1%; sensitivity changed from 0.9122 to 0.9039 (difference, -0.0083; 95% CI, -0.0131 to -0.0035; p < 0.001) and specificity from 0.9659 to 0.9804 (p = 0.334). AI-assisted negative-screening can reduce ophthalmologist workload across multiple retinal diseases, but with disease-specific safety trade-offs: because AI-negative images are not reviewed, reduced sensitivity for DR and AMD means a small proportion of true-positive cases would go undetected, potentially delaying diagnosis and treatment for sight-threatening disease. These results support disease-specific implementation strategies that balance workload reduction against missed positive cases.},
}

@article {pmid42744112,
year = {2026},
author = {Lu, X and Li, B and Sun, B and Fan, S and Chen, N and Chu, Y},
title = {Targeting the choroidal neovascularization microenvironment: new perspectives in nanotherapeutic strategies.},
journal = {European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V},
volume = {},
number = {},
pages = {115238},
doi = {10.1016/j.ejpb.2026.115238},
pmid = {42744112},
issn = {1873-3441},
abstract = {Choroidal neovascularization (CNV) is a key pathological mechanism underlying irreversible vision loss in diseases such as age-related macular degeneration (AMD). Although anti-vascular endothelial growth factor (VEGF) therapies effectively inhibit angiogenesis, they are limited by the need for frequent injections, the tendency to induce resistance, and their inability to reverse the complex pathological microenvironment driving CNV. Research indicates that the initiation and progression of CNV are cooperatively driven by the local microenvironment, particularly through the interplay of oxidative stress, hypoxia, and inflammatory networks. In recent years, the emergence of nanotechnology has provided unprecedented tools for precise modulation of this microenvironment. This review systematically delineates the mechanisms of CNV formation, with a focused analysis on the core interplay between oxidative stress, hypoxia, and inflammation. We provide an in-depth exploration of advanced nano-therapeutic strategies designed to multi-target angiogenic pathways, dynamically manipulate reactive oxygen species, disrupt hypoxia-driven feedback loops, reprogram the immunoinflammatory network, and restore defective cellular autophagy. This review aims to provide a theoretical foundation and forward-looking perspective for developing next-generation microenvironment-targeted therapies capable of intervening in CNV.},
}

@article {pmid42744754,
year = {2026},
author = {Mahato, S and Daniele, E and Lewallen, CF and Sharma, R and Bharti, K},
title = {The Biology and Cell Engineering of Retinal Pigment Epithelium Cell Transplantation: Developing a Living Drug.},
journal = {Annual review of vision science},
volume = {12},
number = {1},
pages = {99-126},
doi = {10.1146/annurev-vision-110725-100948},
pmid = {42744754},
issn = {2374-4650},
mesh = {Humans ; *Retinal Pigment Epithelium/cytology/transplantation ; *Macular Degeneration/therapy/physiopathology ; Animals ; *Cell Engineering/methods ; *Stem Cell Transplantation/methods ; Cell Differentiation/physiology ; Induced Pluripotent Stem Cells/transplantation/cytology ; },
abstract = {Age-related macular degeneration (AMD) is a multifactorial retinal disease that causes progressive vision loss, with retinal pigment epithelium (RPE) atrophy representing a key initiating event. The RPE monolayer plays a crucial role in maintaining photoreceptor and choriocapillaris health and function. In advanced AMD stages, degeneration extends to the photoreceptors and choriocapillaris, likely as a consequence of preceding RPE atrophy. Existing treatment modalities aim to slow disease progression rather than restore degenerated cells and improve visual function. Pluripotent stem cell-derived RPE cell replacement therapy has emerged as a promising approach for restoring native retinal structure and visual function. This review provides an overview of RPE biology and function, clinical-grade manufacturing of RPE transplants, quality control considerations, and the use of scaffolds to improve delivery and integration. We also summarize preclinical and clinical studies that assess the safety, efficacy, and translational potential of RPE transplantation for AMD and other retinal degenerative conditions.},
}

Humans
*Retinal Pigment Epithelium/cytology/transplantation
*Macular Degeneration/therapy/physiopathology
Animals
*Cell Engineering/methods
*Stem Cell Transplantation/methods
Cell Differentiation/physiology
Induced Pluripotent Stem Cells/transplantation/cytology

@article {pmid42744769,
year = {2026},
author = {Muttuvelu, DV and Cehofski, LJ and Faber, C and Falk, MK and Giannaccare, G and Grauslund, J and Hansen, MS and Huemer, J and Keane, PA and Kiruparajan, LP and Larsen, MB and Peto, T and Qin, V and Søndergaard, CB and Taloni, A and Torp-Pedersen, TE and Subhi, Y and Rasmussen, MLR},
title = {Referral patterns after nationwide implementation of OCT-enabled teleophthalmology in optometrist stores in Denmark.},
journal = {European journal of ophthalmology},
volume = {},
number = {},
pages = {11206721261488973},
doi = {10.1177/11206721261488973},
pmid = {42744769},
issn = {1724-6016},
abstract = {PurposeTo evaluate changes in opportunistic eye examination and referral patterns after nationwide implementation of Optical coherence tomography (OCT) within an optometrist-based teleophthalmology pathway.MethodsThis nationwide multi-period observational study included 1,220,082 individuals examined across 79 Danish optometrist stores between March 2022 and May 2025. Data were analyzed across three periods: before OCT, during implementation, and after full implementation. Outcomes included referral rates to teleophthalmology, diagnostic patterns, and referrals to public healthcare.ResultsMonthly referrals to teleophthalmology increased from 703 before OCT to 2,359 after implementation. Detection of macular diseases increased markedly, including central serous chorioretinopathy, epiretinal membrane, macular hole, and neovascular age-related macular degeneration. Referrals to public healthcare rose from 0.55% to 1.74%, with stable acute referrals but substantial increases in subacute (+178%) and routine (+292%) referrals.ConclusionsNationwide implementation of OCT within an optometrist-based teleophthalmology pathway was associated with increased teleophthalmology submissions, increased detection of selected retinal and optic-nerve conditions, and redistribution of public healthcare referrals towards subacute and routine priorities. These findings should be interpreted as changes within an integrated care model combining OCT imaging, standardized optometrist acquisition, consultant ophthalmologist review, and structured teleophthalmology triage, rather than as the isolated effect of OCT.},
}

@article {pmid42744950,
year = {2026},
author = {Pu, J and Hao, X and Zhuang, X and Chen, X and Gan, Y and He, G and Su, Y and He, Y and Li, M and Wen, F},
title = {Geometric and concavity characteristics as diagnostic markers for differentiating nAMD-related MNV from pachychoroid neovascularisation.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42744950},
issn = {1476-5454},
abstract = {PURPOSE: To investigate morphometric differences in macular neovascularisation (MNV) outer contours between neovascular age-related macular degeneration (nAMD) and pachychoroid neovasculopathy (PNV) using quantitative optical coherence tomography angiography (OCTA) analysis.

METHODS: This retrospective cross-sectional study enrolled treatment-naïve patients with newly diagnosed MNV, classified into nAMD and PNV groups. The nAMD group was further subdivided into Type 1 MNV, Type 2 MNV, and polypoidal choroidal vasculopathy (PCV). A semi-automated pipeline integrating FIJI-based contour extraction and custom Python algorithms quantitatively analysed four MNV morphometric domains: geometric parameters, shape descriptors, concavity features, and orientation.

RESULTS: Eighty-nine eyes (89 patients) were included (64 nAMD, 25 PNV). PNV patients were significantly younger (P < 0.001) with better visual acuity (P = 0.026), longer symptom duration (P < 0.001), and greater subfoveal choroidal thickness (P < 0.001). nAMD-related MNV exhibited significantly larger geometric dimensions (all P < 0.05) and deeper marginal indentations (maximum: 0.41 ± 0.33 vs. 0.21 ± 0.14 mm, P = 0.009; mean: 0.17 ± 0.12 vs. 0.10 ± 0.06 mm, P = 0.002) compared to PNV. These differences were more pronounced between PCV and PNV (all P < 0.001). ROC analysis demonstrated moderate discriminative performance for nAMD versus PNV (AUC = 0.711 and 0.723) and good performance for PCV versus PNV (AUC = 0.778 and 0.840) using equivalent diameter and mean concavity depth.

CONCLUSION: Outer contour morphometry effectively differentiates MNV aetiologies, with nAMD (particularly PCV) showing larger, more lobulated patterns than PNV's compact configurations, likely reflecting distinct pathophysiological mechanisms.},
}

@article {pmid42726725,
year = {2026},
author = {Shirakami, M and Miyata, M and Hata, M and Ooto, S and Tamura, H and Otsuka, A and Tsukui, L and Ueda-Arakawa, N and Miyake, M and Takahashi, A and Kadomoto, S and Muraoka, Y and Tsujikawa, A},
title = {Two-dose aflibercept 8 mg versus three-dose aflibercept 2 mg loading for treatment-naïve neovascular age-related macular degeneration.},
journal = {PloS one},
volume = {21},
number = {9},
pages = {e0349947},
pmid = {42726725},
issn = {1932-6203},
mesh = {*Receptors, Vascular Endothelial Growth Factor/administration & dosage/therapeutic use ; *Recombinant Fusion Proteins/administration & dosage/therapeutic use ; Humans ; Retrospective Studies ; Female ; Male ; Visual Acuity/drug effects ; *Macular Degeneration/drug therapy/pathology ; Intravitreal Injections ; Aged ; Aged, 80 and over ; Treatment Outcome ; *Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Dose-Response Relationship, Drug ; },
abstract = {This retrospective study compared the short-term efficacy of a two-dose intravitreal aflibercept (IVA) 8-mg loading regimen (2024-2025) with a conventional three-dose IVA 2-mg regimen (2013-2014) for treatment-naïve neovascular age-related macular degeneration (nAMD). Using 1:1 propensity score matching for age, sex, nAMD subtype, and baseline visual acuity, we evaluated 31 eyes per group. The primary endpoint was the proportion of eyes achieving a fluid-free center subfield one month after completing the respective loading phase (at 2 and 3 months from baseline, respectively). The fluid-free proportion was numerically higher in the 8-mg group (90.3%; 95% confidence interval [CI], 74.2-98.0%) than in the 2-mg group (80.6%; 95% CI, 62.5-92.5%); however, the difference was not statistically significant (P = 0.28). Both regimens yielded significant reductions in central retinal thickness, central choroidal thickness, and pigment epithelial detachment height, with no significant between-group differences. Within the 8-mg group, baseline intraretinal fluid strongly correlated with one-month visual acuity (r = 0.61, P < 0.001). These exploratory findings suggest that a reduced two-dose aflibercept 8-mg loading regimen provided short-term anatomical outcomes that did not differ significantly from the standard three-dose 2-mg regimen. This shortened loading phase potentially reduces the initial treatment burden. Further prospective studies should validate these preliminary outcomes.},
}

*Receptors, Vascular Endothelial Growth Factor/administration & dosage/therapeutic use
*Recombinant Fusion Proteins/administration & dosage/therapeutic use
Humans
Retrospective Studies
Female
Male
Visual Acuity/drug effects
*Macular Degeneration/drug therapy/pathology
Intravitreal Injections
Aged
Aged, 80 and over
Treatment Outcome
*Angiogenesis Inhibitors/administration & dosage/therapeutic use
Dose-Response Relationship, Drug

@article {pmid42726829,
year = {2026},
author = {Kolot, NM and Shargorodska, IV and Ivaniuta, PP and Kovalov, IA and Averyanova, OS},
title = {Factors assoсiated with ocular structural changes inherent to pseudoexfoliation syndrome among Ukrainian patients.},
journal = {Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego},
volume = {54},
number = {4},
pages = {472-477},
doi = {10.36740/Merkur202604114},
pmid = {42726829},
issn = {1426-9686},
mesh = {Humans ; *Exfoliation Syndrome/pathology/complications/epidemiology ; Aged, 80 and over ; Female ; Male ; Middle Aged ; Aged ; Ukraine/epidemiology ; Adult ; Adolescent ; Young Adult ; Risk Factors ; },
abstract = {OBJECTIVE: Aim: To identify factors associated with ocular structural changes inherent to PEX among Ukrainian patients.

PATIENTS AND METHODS: Materials and Мethods: The study was based on a clinical examination of 56 patients (112 eyes) aged 14 to 88 years. The main group included 39 patients (78 eyes) with ocular structural changes confirming the diagnosis of PEX: 14 patients (28 eyes) and 25 patients (50 eyes) with uni- and bilateral lateral involvement, respectively. The control group consisted of 17 patients (34 eyes) without any signs of PEX. The follow-up period was 5 years.

RESULTS: Results: The findings of the study support the concept of PEX as a systemic fibrillopathy, accompanied by a significant association with chronic coronary syndrome (64%), joint pathology (72%), diabetes mellitus (40%), and central nervous system (56%) disorders compared with the control group. Environmental factors, particularly urbanization (52%) and increased radiation background (64%), are likely additional contributors to disease development. The study demonstrated that bilateral PEX is accompanied by changes in eye structures: pronounced trabecular pigmentation (48%), a critical decrease in corneal endothelial cell density (80%), progression of age-related macular degeneration (40-44%), and the development of posterior subcapsular cataract (96%). In contrast, patients with unilateral PEX demonstrated a significantly higher long-term risk of nuclear cataract progression.

CONCLUSION: Conclusions: Managing patients with PEX necessitates a comprehensive multidisciplinary approach in view of the associated comorbidities and contributing factors. The clinical course of unilateral PEX is strongly linked to exposure to exogenous triggers (urbanization, increased background radiation, and tobacco smoking). The absolute majority of eyes with bilateral PEX showed biomechanical weakness of the sclera and cornea.},
}

Humans
*Exfoliation Syndrome/pathology/complications/epidemiology
Aged, 80 and over
Female
Male
Middle Aged
Aged
Ukraine/epidemiology
Adult
Adolescent
Young Adult
Risk Factors

@article {pmid42727684,
year = {2026},
author = {Shen, M and Lam, WZ and Berni, A and Herrera, G and El-Mulki, OS and Badla, O and Herrera, E and Liu, J and Cheng, Y and Kastner, J and Trivizki, O and Meng, D and Patel, P and Kumar, S and Zhang, Y and Le, VH and O'Brien, RC and Nicola, MD and Yehoshua, Z and Dubovy, SR and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Two-Year Experience with Intravitreal Pegcetacoplan for the Treatment of Geographic Atrophy in Clinical Practice.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.09.011},
pmid = {42727684},
issn = {1879-1891},
abstract = {PURPOSE: To report the 2-year experience of using intravitreal pegcetacoplan for the treatment of geographic atrophy (GA) in age-related macular degeneration (AMD).

DESIGN: Retrospective interventional case series.

METHODS: Eyes with symptomatic GA secondary to AMD were treated with 15mg of intravitreal pegcetacoplan and participated in an ongoing prospective swept-source optical coherence tomography angiography (SS-OCTA) imaging study. All eyes underwent SS-OCTA imaging before and during pegcetacoplan therapy to assess for GA lesion size, the presence of non-exudative macular neovascularization (MNV), and the onset of exudation. The growth rate of GA and best-corrected visual acuity (BCVA) were assessed for all eyes treated for 2 years.

RESULTS: From April 12, 2023 to December 8, 2025, 77 eyes from 58 patients continued pegcetacoplan treatment for 2 years. Eyes received an average of 18±3 injections with an interval of 1.3 months between injections. For the 72 eyes with 2 years of follow-up and measurable GA, the square-root (sqrt) GA growth rate after pegcetacoplan treatment was 0.22±0.12 mm/year. Of the 72 eyes, 71 eyes either decreased further in their sqrt GA growth rate or remained the same in the second year, while 1 eye had an increase in the sqrt GA growth rate. This eye also received concomitant anti-VEGF therapy due to exudative MNV. Of these 72 eyes, 49 eyes had prior annual visits before treatment. In these eyes, the annual sqrt GA growth rate was 0.33±0.21 mm/year before pegcetacoplan and 0.19±0.11 mm/year after 2 years, resulting in a 41% decrease in the growth rate (p<0.001). There were no significant differences in GA growth rates between foveal and non-foveal GA (all p≥0.99). The mean BCVA declined from 63±14 to 55±16 letters over 2 years (p<0.001), with no significant difference between foveal and non-foveal GA (p=0.14). Positive correlations were found between the sqrt GA growth rates prior to treatment and the percent growth inhibition over both 1 year (r=0.33, p=0.02) and 2 years of treatment (r=0.40, p=0.007).

CONCLUSIONS: Pegcetacoplan therapy reduced the growth rate of GA by about 41% over 2 years and continued to show accumulated efficacy during the second year.},
}

@article {pmid42728439,
year = {2026},
author = {Golebka, JP and Josan, AS and Mi, H and Mole, G and Aslam, SA and MacLaren, RE and Cehajic-Kapetanovic, J},
title = {Comparison of current treatment strategies for AMD-related submacular haemorrhage: Real-world outcomes.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42728439},
issn = {1435-702X},
abstract = {PURPOSE: Comparison of available treatment modalities for neovascular AMD-related submacular haemorrhage including robot-assisted subretinal drug delivery.

METHODS: Single centre, long-term, retrospective analysis of patients treated for nAMD-related submacular haemorrhage. For each treatment group, outcomes assessed included haemorrhage resolution and best corrected visual acuity (BCVA) change with sub-analyses by haemorrhage size.

RESULTS: We identified 55 patients with classic nAMD-related submacular haemorrhage. We observed a preference for the surgical approach injecting subretinal TPA (manual or robotic) with intravitreal anti-VEGF and pneumatic displacement (30 cases: 8:10:12 ratio of small:medium:large haemorrhage), over intravitreal TPA/anti-VEGF/pneumatic displacement (13 cases: 4:5:4) or intravitreal anti-VEGF alone (12 cases 8:4:0). Subretinal TPA led to significant decrease in haemorrhage size by month 1 compared to intravitreal TPA or anti-VEGF monotherapy (p < 0.0001, Tukey test) with most cases resolving by 12 months irrespective of the treatment group. Mean BCVA change over 12 months was not significantly different between treatment groups, although by 12 months + 15 letter gain was observed post subretinal TPA, + 11 after intravitreal TPA and -7 letters loss after anti-VEGF monotherapy. A higher proportion of patients in the surgical group (53% subretinal and 69% intravitreal TPA) were associated with BCVA improvement, or stabilisation (33% and 15% respectively), while anti-VEGF alone led to more frequent BCVA deteriorations (50% of cases). Robot-assisted TPA injection showed comparable result to the manual technique.

CONCLUSIONS: Subretinal TPA approach, manual and robotic, resulted most effective clearance of submacular haemorrhage in the early post-operative phase, with some potential clinical benefit for longer term visual function.},
}

@article {pmid42732817,
year = {2026},
author = {Fujimoto, S and Kokame, GT and Kawasaki, R and Hara, C and Omizo, JN and Nishida, K},
title = {Variations in the clinical characteristics of geographic atrophy among Caucasians, Japanese Americans in Hawaii, and Japanese in Japan.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100372},
doi = {10.1016/j.apjo.2026.100372},
pmid = {42732817},
issn = {2162-0989},
abstract = {PURPOSE: To compare clinical characteristics of geographic atrophy (GA) among Caucasians in Hawaii (C-A), Japanese Americans in Hawaii (J-A), and Japanese in Japan (J-J).

DESIGN: Retrospective study.

METHODS: Consecutive patients with GA were recruited from single institutions in Hawaii and Japan, and GA areas within 6×6mm² OCT scan area were measured on near-infrared images obtained at the latest visit. Ethnic differences in GA-related characteristics were assessed using mixed-effects models adjusted for age and sex. All values are means.

RESULTS: A total of 125 eyes from 91 patients were included: 51 eyes of 36 C-A (58% men), 36 eyes of 26 J-A (35% men), and 38 eyes of 29 J-J (69% men). Bilateral GA was more frequent in C-A (72%) than in J-J (34%, P < 0.01), while J-A (50%) did not differ from either group. The number of GA foci was greater in C-A (2.8) than in J-A (1.9, P < 0.05) and J-J (1.5, P < 0.01). GA area was significantly larger in C-A (10.3mm²) than in J-J (8.8mm², P < 0.05), with J-A (6.0mm²) intermediate. Subfoveal choroidal thickness (SFCT) was thinner in C-A (83.3µm) than in J-A (140.8µm, P < 0.001) and J-J (165.3µm, P < 0.0001).

CONCLUSIONS: The number of GA foci and SFCT differed between J-J and C-A as well as between J-A and C-A, suggesting genetic differences. In contrast, significant differences in GA area and bilaterality were observed only between J-J and C-A. The intermediate values in J-A may reflect environmental influences. Further studies are warranted.},
}

@article {pmid42733609,
year = {2026},
author = {Piedrahita, MA and Arias-Ortiz, WA and Acosta Cadavid, CP and Cadena Galvis, E and Peña, FY},
title = {Patient-Reported Quality of Life and Treatment Experiences Among Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Aflibercept in Colombia: A Qualitative Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {626968},
pmid = {42733609},
issn = {1177-5467},
abstract = {PURPOSE: To explore the experiences and perceptions of patients with neovascular age-related macular degeneration (AMD) receiving anti-VEGF therapy and understand how treatment influences their quality of life.

PATIENTS AND METHODS: A qualitative study informed by a phenomenological perspective and employing a hybrid deductive-inductive thematic analysis was conducted at an ophthalmologic center in Medellín, Colombia. Fourteen patients with confirmed AMD undergoing intravitreal aflibercept treatment participated in semi-structured telephone interviews. Participants were selected through purposive sampling until meaning saturation was achieved, defined as the point at which no new experiential themes emerged. Interviews were transcribed verbatim and analyzed using a hybrid deductive-inductive thematic analysis guided by the Felce and Perry quality-of-life framework, supported by ATLAS.ti v24.

RESULTS: Patients described AMD as a condition strongly associated with fear, uncertainty, and emotional distress, particularly related to progressive visual loss and blindness. Intravitreal injections were initially perceived as invasive and anxiety-provoking; however, over time many participants associated treatment with hope, visual stability, and preservation of independence. Family support, religious beliefs, and trust in the treating ophthalmologist emerged as important factors for emotional coping and treatment adherence. Participants also reported subjective improvement in daily activities such as reading, mobility, self-care, and social interaction. Nevertheless, some continued to experience limitations related to transportation, dependence on others, and social isolation. Concerns about continuity of care and access to medication were frequently expressed.

CONCLUSION: Quality of life in patients with AMD receiving anti-VEGF therapy extends beyond visual outcomes alone and is deeply influenced by emotional, social, and functional factors. Although treatment generated fear and discomfort at the beginning, it also represented an opportunity to maintain autonomy and social participation. These findings highlight the importance of patient-centered care strategies that integrate psychosocial support, clear communication, and continuous access to treatment.},
}

@article {pmid42734305,
year = {2026},
author = {Ehrenzeller, C and Cancian, G and Kostin, V and Peyla, A and Ansari, G and Paris, A and Grimaldi, G and Pfau, M and Menghini, M},
title = {Clinical Surrogate Endpoints in Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Findings From a Two-Year Natural History Study.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {11},
pages = {24},
pmid = {42734305},
issn = {1552-5783},
mesh = {Humans ; Female ; Tomography, Optical Coherence/methods ; Male ; Middle Aged ; Visual Acuity/physiology ; Aged ; Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology ; Retinal Drusen/physiopathology ; Visual Field Tests ; *Corneal Dystrophies, Hereditary/physiopathology/diagnosis ; Disease Progression ; Visual Fields/physiology ; Multimodal Imaging ; *Retinal Dystrophies/physiopathology/diagnosis ; Optic Disk Drusen/congenital ; },
abstract = {PURPOSE: Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy is a rare, inherited retinal dystrophy characterized by drusen formation and early vision loss. Its phenotypical similarities with dry age-related macular degeneration (AMD) make Malattia Leventinese a valuable monogenetic disease model for AMD. Identifying sensitive outcome measures is crucial for clinical trials. This study quantifies retinal pigment epithelium and drusen complex (RPEDC) increase and retinal layer degeneration using fully automated segmentation for multimodal imaging analysis, and investigates structural thresholds associated with functional decline through pointwise correlation.

METHODS: This multicenter cohort study included 25 patients (15 women and 10 men; median age = 60 years, interquartile range [IQR] = 51-73 years) with genetically confirmed Malattia Leventinese. Participants underwent multimodal imaging, including spectral-domain optical coherence tomography (SD-OCT), ultrawide fundus retinography and fundus autofluorescence (FAF), and mesopic and two-color scotopic microperimetry. Changes in retinal layer thicknesses and retinal sensitivity were assessed over 2 years using linear mixed-effects models, and structure-function breakpoints were estimated with piecewise models.

RESULTS: RPEDC thickness increased (+2.24 µm/y), whereas photoreceptor inner segments (-0.70 µm/y) and outer nuclear layer (-1.95 µm/y) thicknesses, in addition to choroidal thickness (-10.83 µm/y), decreased with disease progression. Total retinal thickness remained stable. Scotopic sensitivity declined over time, with -0.40 decibel (dB)/year at 505 nm and -0.37 dB/year at 627 nm, whereas mesopic sensitivity remained stable. Function decreased most in early disease stages, with the onset of drusen accumulation.

CONCLUSIONS: In Malattia Leventinese, the total retinal thickness remains unchanged because the RPEDC increase offsets the thinning of outer retinal layers. Only scotopic function decreases significantly with progression and before the age of 55 years. Mesopic function may serve to track later stages. These findings support the outer nuclear layer and photoreceptor inner segment thicknesses as key structural endpoints and scotopic sensitivity as an early functional outcome measure for monitoring disease progression in ongoing and future clinical trials.},
}

Humans
Female
Tomography, Optical Coherence/methods
Male
Middle Aged
Visual Acuity/physiology
Aged
Fluorescein Angiography/methods
*Retinal Pigment Epithelium/pathology
Retinal Drusen/physiopathology
Visual Field Tests
*Corneal Dystrophies, Hereditary/physiopathology/diagnosis
Disease Progression
Visual Fields/physiology
Multimodal Imaging
*Retinal Dystrophies/physiopathology/diagnosis
Optic Disk Drusen/congenital

@article {pmid42734658,
year = {2026},
author = {Maeda, K and Machida, A and Murakami, R and Akiyama, F and Miyagi, S and Oishi, A},
title = {Fellow-eye retinal age gap and high injection burden over four years in neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42734658},
issn = {1435-702X},
support = {22K09793//Japan Society for the Promotion of Science/ ; 25K20183//Japan Society for the Promotion of Science/ ; },
abstract = {PURPOSE: To evaluate whether fellow-eye retinal age gap (RAG), estimated using a deep learning model, is associated with long-term intravitreal injection burden in treatment-naive neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective cohort study included 80 patients with treatment-naive nAMD followed for ≥ 4 years after initiating anti-vascular endothelial growth factor therapy. Retinal age was estimated from fellow-eye fundus photographs using the publicly available Japan Ocular Imaging Registry model, and raw RAG was calculated as retinal age minus chronological age. Univariable analyses assessed associations of retinal age metrics with baseline ocular parameters, whereas univariable and multivariable analyses assessed their associations with 4-year injection burden.

RESULTS: Median chronological age, retinal age, and raw RAG were 67.6, 68.9, and 1.33 years, respectively. Retinal age correlated with baseline best-corrected visual acuity and central retinal thickness, while raw RAG correlated with central choroidal thickness. Neither raw nor age-corrected RAG was associated with total injection number in the count analysis. In an exploratory threshold-based analysis, the ≥ 24-injection group had higher raw RAG than the < 24-injection group (4.19 vs. 0.66 years, P = 0.039), and higher raw RAG was associated with requiring ≥ 24 injections (OR 1.11 per 1-year increase; 95% CI, 1.01-1.22; P = 0.029). However, this association was attenuated after age correction and was not replicated at alternative thresholds.

CONCLUSION: Higher raw fellow-eye RAG was associated with the ≥ 24-injection threshold; the association was attenuated after age correction and nonsignificant in alternative-threshold and count analyses. Further studies should evaluate RAG as a fundus-based candidate marker of sustained high treatment burden.},
}

@article {pmid42736398,
year = {2026},
author = {Bousamri, A},
title = {Comment on: 'Aflibercept 8 mg in neovascular age-related macular degeneration and diabetic macular oedema'.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42736398},
issn = {1476-5454},
}

@article {pmid42736891,
year = {2026},
author = {Öncül, H and Dağ, U and Alakuş, MF},
title = {Regular AREDS2 Supplement Use in Age-Related Macular Degeneration: Factors Associated with Supplementation, Medication Adherence, and Patient-Reported Barriers.},
journal = {Healthcare (Basel, Switzerland)},
volume = {14},
number = {17},
pages = {},
pmid = {42736891},
issn = {2227-9032},
abstract = {Background/Objectives: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment, and AREDS2-based nutritional supplementation is recommended for clinically eligible patients to reduce the risk of disease progression. However, successful implementation depends on regular supplement use and sustained adherence. This study investigated demographic, socioeconomic, clinical, and physician-related factors associated with regular AREDS2 supplement use and evaluated medication adherence, physician counseling, and patient-reported barriers among clinically eligible patients with AMD. Methods: In this single-center cross-sectional study, 389 patients with intermediate AMD or advanced AMD in one eye who fulfilled the indications for AREDS2 supplementation were enrolled. Participants reporting occasional supplement use were excluded. A structured interviewer-administered questionnaire was used to collect demographic, socioeconomic, and clinical data, together with information on physician recommendation, medication adherence, patient knowledge, and perceived barriers to supplementation. Factors associated with regular AREDS2 supplement use were evaluated using univariable and multivariable logistic regression analyses, whereas adherence patterns and patient-reported barriers were analyzed descriptively. Results: Of the 389 participants, 273 (70.2%) reported regular AREDS2 supplement use, whereas 116 (29.8%) were non-users. Multivariable analysis showed that younger age, educational attainment, and physician recommendation were independently associated with regular supplement use (adjusted OR for physician recommendation, 5.38; 95% CI, 2.68-10.81; p < 0.001). Among regular users, 53.5% met the study-defined criteria for good medication adherence. The most frequently reported barriers among non-users were financial burden, limited supplement availability, polypharmacy, and insufficient knowledge regarding AREDS2 supplementation. Conclusions: Regular AREDS2 supplement use among clinically eligible patients with AMD was associated with demographic, educational, and physician-related factors, whereas long-term adherence remained suboptimal despite substantial uptake. These findings emphasize the importance of effective physician counseling, structured patient education, and interventions addressing socioeconomic barriers to improve the real-world implementation of evidence-based nutritional supplementation in AMD.},
}

@article {pmid42737684,
year = {2026},
author = {Panos, GD and Empeslidis, T and Amaxilati, E and Tsiropoulos, GN and Topouzis, N and Konstas, PAG and Chatzimichail, E and Gatzioufas, Z and Amoaku, W},
title = {Molecular Determinants of Intravitreal Anti-VEGF Durability: Drug Architecture, Intraocular Pharmacokinetics, Target Biology and Treatment Resistance.},
journal = {International journal of molecular sciences},
volume = {27},
number = {17},
pages = {},
pmid = {42737684},
issn = {1422-0067},
mesh = {Humans ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism ; *Angiogenesis Inhibitors/pharmacokinetics/administration & dosage/therapeutic use/pharmacology ; Intravitreal Injections ; Animals ; Drug Resistance ; *Macular Degeneration/drug therapy/metabolism ; Eye/metabolism/drug effects ; Macular Edema/drug therapy/metabolism ; Ranibizumab/pharmacokinetics/therapeutic use ; },
abstract = {Intravitreal inhibition of vascular endothelial growth factor (VEGF) has transformed the management of neovascular age-related macular degeneration, diabetic macular oedema and macular oedema secondary to retinal vein occlusion, but frequent monitoring and retreatment remain major burdens. Ocular half-life is often used as shorthand for durability, although the clinical interval is produced by a wider molecular and biological system. This narrative review examines how dose, molecular format, hydrodynamic size, binding affinity, valency, ligand spectrum, target turnover, tissue distribution and delivery architecture determine the time for which an eye remains controlled. Human ocular pharmacokinetic and pharmacodynamic evidence is interpreted according to compartment, assay and model provenance, with particular attention to the distinction between drug elimination, free-ligand suppression, anatomical control and protocol-assigned treatment interval. Trial evidence for ranibizumab, aflibercept, conbercept, brolucizumab and faricimab shows that extended dosing can arise from greater starting exposure, altered binding architecture or pathway expansion without a proportionate change in intrinsic ocular half-life. Patient phenotype and retreatment rules further modify the observed interval. Refillable reservoirs, biodegradable depots and ocular gene therapy change the governing kinetics from bolus elimination to controlled release or sustained local production, thereby increasing the importance of reversibility and cumulative safety. We propose that durability be defined as a time-to-threshold phenotype integrating active target-site exposure, biological demand, anatomical recurrence, all treatment-related procedures and safety. Standardised estimands, longitudinal human ocular sampling, spatial exposure methods and externally validated mechanism-informed models are needed to make molecular durability comparable and clinically actionable.},
}

Humans
*Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
*Angiogenesis Inhibitors/pharmacokinetics/administration & dosage/therapeutic use/pharmacology
Intravitreal Injections
Animals
Drug Resistance
*Macular Degeneration/drug therapy/metabolism
Eye/metabolism/drug effects
Macular Edema/drug therapy/metabolism
Ranibizumab/pharmacokinetics/therapeutic use

@article {pmid42738828,
year = {2026},
author = {Mehta, P and Moore, E and Dash, A and Shukla, S},
title = {Liposomal Drug Delivery in Ocular Therapy: Strategies for Enhancing Corneal Penetration and Bioavailability.},
journal = {Cells},
volume = {15},
number = {17},
pages = {},
pmid = {42738828},
issn = {2073-4409},
mesh = {Humans ; *Liposomes/chemistry ; Biological Availability ; *Drug Delivery Systems/methods ; *Cornea/metabolism/drug effects ; Animals ; Administration, Ophthalmic ; *Eye Diseases/drug therapy ; Ophthalmic Solutions ; },
abstract = {Vision impairment affects approximately 2.2 billion people worldwide, with glaucoma, age-related macular degeneration, fungal keratitis, and diabetic retinopathy among the leading causes of preventable blindness. Effective pharmacotherapy remains severely constrained by the eye's multilayered barrier architecture. Tear film, the corneal epithelium, the blood-aqueous barrier, and the blood-retinal barrier collectively restrict conventional topical drug bioavailability to less than 5% of the administered dose. Liposomal drug delivery systems have emerged as a clinically translatable platform capable of overcoming these barriers through targeted surface modification. This review provides a brief introduction to ocular barriers to drug delivery and transport and critically examines numerous surface-modification strategies applied to liposomal carriers to enhance corneal permeation and ocular bioavailability of drugs. It highlights the advantages and disadvantages of each modification strategy, as well as the convergent mechanism of liposomal surface modification in overcoming ocular barriers, and provides a comparative analysis of different surface-modification strategies of liposomes in terms of safety, efficacy and corneal retention. Additionally, it describes challenges associated with liposomal ophthalmic formulations in industrial scaling up. The review also sheds light on some FDA-approved liposomal ophthalmic products, active clinical trials on liposomal formulations, and relevant patents, demonstrating the potential benefits of liposomal drug delivery in the treatment of ocular disorders.},
}

Humans
*Liposomes/chemistry
Biological Availability
*Drug Delivery Systems/methods
*Cornea/metabolism/drug effects
Animals
Administration, Ophthalmic
*Eye Diseases/drug therapy
Ophthalmic Solutions

@article {pmid42739139,
year = {2026},
author = {Baek, J and Oh, R and Park, D and Bae, K},
title = {Evaluating Artificial Intelligence as a First-Pass Reader in Fundus Photograph Screening: A Multireader Workflow Validation Study.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {17},
pages = {},
pmid = {42739139},
issn = {2075-4418},
support = {SNUH 0620242810//VUNO Inc/ ; KMI20260230//2026 research program of the Korea Medical Institute/ ; },
abstract = {Background/Objectives: Double reading with arbitration improves diagnostic reliability in fundus screening but requires repeated human interpretation. Whether artificial intelligence (AI) can serve as a first-pass decision source within this workflow, and whether this applies consistently across retinal diseases with differing inter-reader agreement, remains unclear. Methods: In this retrospective study, 6904 color fundus photographs from 2593 patients at a tertiary screening center were analyzed for age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Three retina specialists independently labeled each image, and an AI system provided binary classifications at a prespecified operating threshold targeting 0.99-sensitivity. In AI-human double reading, the AI and one reader independently interpreted each image, and a second reader arbitrated discordant cases; this was compared with conventional human-human double reading. Three reader combinations were evaluated per disease. Results: AI-human reading required 1.02-1.11 human reads per image versus 2.00-2.10 for human-human reading. For DR and RVO, human-human reading yielded sensitivities of 0.974 and 0.982 and specificities of 0.999 and 1.000, respectively. Across AI-human combinations, sensitivity and specificity did not differ significantly from human-human reading (all p ≥ 0.05; specificity differences ≤0.001). For AMD (human-human sensitivity 0.845, specificity 1.000), AI-human sensitivity varied: two combinations were higher (0.916 and 0.950; both p < 0.001) and one comparable (0.842; p = 0.742). AMD specificity remained ≥0.978. Conclusions: AI-human reading halved human reading volume without significant loss for DR and RVO; AMD varied by configuration. AI use within double-reading workflows should account for disease-specific inter-reader agreement, reader composition, and operating threshold. This was a single-center, retrospective study, prospective external validation in a multicenter setting is warranted before clinical implementation.},
}

@article {pmid42739742,
year = {2026},
author = {Sato, T},
title = {The Eight-Chop Technique in Nonagenarian Patients: Real-World Intraoperative and Postoperative Outcomes.},
journal = {Journal of clinical medicine},
volume = {15},
number = {17},
pages = {},
pmid = {42739742},
issn = {2077-0383},
abstract = {Objectives: To describe intraoperative and postoperative outcomes of the Eight-Chop Technique in elderly patients, with particular attention to nonagenarian patients undergoing cataract surgery. Methods: This retrospective study included consecutive eligible eyes undergoing Eight-Chop phacoemulsification and posterior chamber intraocular lens implantation at a single clinic. Eyes were stratified by age at surgery into 70-79 years, 80-89 years, and ≥90 years groups. Sixty eyes were included in each younger group, and all 49 eligible nonagenarian eyes were included. Eyes were not intentionally excluded from the younger groups because of poor pupillary dilation, zonular weakness, white cataract, pseudoexfoliation, glaucoma, age-related macular degeneration, or advanced nuclear grade. Preoperative characteristics, intraoperative parameters, best-corrected visual acuity (BCVA), intraocular pressure, and corneal endothelial cell density (CECD) were evaluated. Linear mixed-effects models accounted for fellow-eye correlation. Results: A total of 169 eyes were analyzed. The ≥90-year cohort had greater baseline complexity; intraoperative differences were descriptive, with the highest operative time, phacoemulsification time, aspiration time, cumulative dissipated energy, and irrigation fluid volume (all p < 0.001). Postoperative BCVA improved from baseline in all groups. Mean CECD loss at 19 weeks was -1.3 ± 5.7%, -0.7 ± 5.7%, and 3.5 ± 9.2% in the 70-79-, 80-89-, and ≥90-year groups, respectively. No serious intraoperative complications occurred. Conclusions: The Eight-Chop Technique was used across elderly age groups, including nonagenarian patients. Observed age-group differences represent associations in this retrospective dataset and do not establish causal age effects or comparative superiority, safety, or endothelial protection of the technique.},
}

@article {pmid42739837,
year = {2026},
author = {Kook, K and Park, D and Lee, G and Ji, YS},
title = {Time to Exudative Recurrence After Complete Fluid Resolution Following Anti-VEGF Loading in Neovascular Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {15},
number = {17},
pages = {},
pmid = {42739837},
issn = {2077-0383},
abstract = {Background/Objectives: The timing of exudative recurrence after complete fluid resolution following anti-vascular endothelial growth factor (anti-VEGF) loading in neovascular age-related macular degeneration (nAMD) is unpredictable. We prespecified two questions: whether the speed of fluid resolution during loading, or the baseline pigment epithelial detachment (PED) type, predict recurrence timing. Methods: We retrospectively analyzed 72 treatment-naïve nAMD eyes that achieved complete resolution of subretinal fluid (SRF) and intraretinal fluid (IRF) after three monthly loading injections, then observed them under a pro re nata strategy. Time from the post-loading dry-confirmation visit to first detected recurrence was analyzed with Kaplan-Meier and Cox models; baseline variables with univariable p < 0.10 were entered into a multivariable model. Results: Recurrence was detected in 58 eyes (80.6%); median recurrence-free survival was 139 days (95% CI, 118-158). Resolution of SRF or IRF by one month was not significantly associated with recurrence timing (p = 0.586 and 0.054). Fibrovascular PED was associated with earlier detected recurrence compared with non-fibrovascular PED (adjusted hazard ratio 2.40, 95% CI, 1.17-4.92; p = 0.017; median 130 vs. 602 days). Eyes with fibrovascular PED were monitored more frequently, but the association persisted in an interval-censored sensitivity analysis (adjusted HR 2.71, 95% CI, 1.32-5.60). Conclusions: The speed of fluid resolution was not significantly associated with recurrence timing, whereas fibrovascular PED was associated with earlier detected recurrence and may represent a candidate prognostic marker requiring prospective validation.},
}

@article {pmid42739959,
year = {2026},
author = {Sun, X and Lin, W and Yuan, C and Xu, J and Luo, Y},
title = {Self-Supervised OCT Representation Learning with Local Dimensionality Regularization for Automated Retinal Disease Diagnosis.},
journal = {Sensors (Basel, Switzerland)},
volume = {26},
number = {17},
pages = {},
pmid = {42739959},
issn = {1424-8220},
support = {2023YFC3402800//National Key Research and Development Program of China/ ; 62501292//National Natural Science Foundation of China/ ; BK2023200//Jiangsu Province Science and Technology Department/ ; 24KJB520020//Natural Science Research of Jiangsu Higher Education Institutions of China/ ; },
mesh = {*Tomography, Optical Coherence/methods ; Humans ; Representation Machine Learning ; *Retinal Diseases/diagnostic imaging/diagnosis ; Retina/diagnostic imaging ; Algorithms ; Supervised Machine Learning ; Image Processing, Computer-Assisted/methods ; Macular Degeneration/diagnostic imaging/diagnosis ; Diabetic Retinopathy ; },
abstract = {Optical coherence tomography (OCT) is a high-resolution and non-contact optical imaging and sensing modality that provides depth-resolved cross-sectional visualization of retinal microstructures. It plays an important role in the assessment of retinal diseases, including age-related macular degeneration (AMD) and diabetic macular edema (DME). However, automated OCT image classification commonly relies on fully supervised models that require large-scale expert annotations, which are costly and time-consuming because of the complex layered anatomy and subtle pathological patterns present in retinal OCT images. To reduce annotation dependence, this study proposes a self-supervised representation learning framework with local dimensionality regularization for retinal OCT image classification. The proposed method estimates the local intrinsic dimensionality of learned representations and incorporates it into an asymptotic Fisher-Rao regularization objective to mitigate local dimensional degeneration and preserve fine-grained structural information. Logarithmic scaling and geometric averaging are further introduced to reduce sensitivity to outliers and improve optimization stability. Experiments on three independent OCT datasets achieved classification accuracies of 94.35%, 92.48%, and 92.56%, respectively, demonstrating competitive performance compared with mainstream self-supervised methods. These results demonstrate that explicitly modeling local feature geometry can improve the discrimination of sensor-acquired OCT images while reducing reliance on manual annotations, providing an effective approach for intelligent analysis of biomedical optical imaging data.},
}

*Tomography, Optical Coherence/methods
Humans
Representation Machine Learning
*Retinal Diseases/diagnostic imaging/diagnosis
Retina/diagnostic imaging
Algorithms
Supervised Machine Learning
Image Processing, Computer-Assisted/methods
Macular Degeneration/diagnostic imaging/diagnosis
Diabetic Retinopathy

@article {pmid42723073,
year = {2026},
author = {Tom, E and Gao, F and Franco, CN and Wong, A and Kemmerer, N and Wang, Z and Jairaman, A and Xu, Q and Zhuang, Y and Du, SW and Palczewska, G and Palczewski, K and Budin, I and Othy, S and Shi, X and Bonilha, VL and Schoeneberg, J and Wahlin, KJ and Albrecht, LV and Skowronska-Krawczyk, D},
title = {Lipid-driven membrane remodeling engages a lysosome-dependent adaptive repair program during retinal aging.},
journal = {Molecular neurodegeneration},
volume = {21},
number = {1},
pages = {},
pmid = {42723073},
issn = {1750-1326},
mesh = {*Lysosomes/metabolism ; Animals ; *Aging/metabolism ; *Retinal Pigment Epithelium/metabolism/pathology ; *Macular Degeneration/metabolism/pathology ; *Cell Membrane/metabolism ; Fatty Acid Elongases/metabolism ; Mice ; *Membrane Lipids/metabolism ; Acetyltransferases/metabolism ; Humans ; *Retina/metabolism ; },
abstract = {Age-associated remodeling of membrane lipid composition has been implicated in cellular dysfunction, yet the mechanisms linking lipid changes to membrane integrity and disease remain poorly defined. In the retinal pigment epithelium (RPE), lipid dysregulation is strongly associated with aging and age-related macular degeneration (AMD), a neurodegenerative disease of the central nervous system, but the causal pathways remain unclear. Here, we identify reduced activity of the lipid elongase ELOVL2 as a central driver of age-dependent membrane remodeling. Loss of ELOVL2-dependent polyunsaturated fatty acid (PUFA) elongation shifts plasma membrane lipid composition, leading to altered membrane biophysical properties and compromised membrane integrity. In response to this stress, RPE cells do not undergo apoptosis but instead activate a lysosome-dependent plasma membrane repair program that preserves barrier function under metabolic challenge. However, this adaptive response drives spatially polarized lysosomal exocytosis, promoting extracellular remodeling and accumulation of sub-RPE deposits associated with aging and AMD. Restoration of ELOVL2-derived lipid products reverses membrane abnormalities and suppresses lysosome-mediated remodeling phenotypes, demonstrating direct metabolic control of membrane homeostasis. Together, these findings define an ELOVL2-dependent lipid-lysosome axis that links PUFA elongation to plasma membrane integrity and reveals how compensatory repair mechanisms can contribute to tissue remodeling and disease progression in aging epithelia.},
}

*Lysosomes/metabolism
Animals
*Aging/metabolism
*Retinal Pigment Epithelium/metabolism/pathology
*Macular Degeneration/metabolism/pathology
*Cell Membrane/metabolism
Fatty Acid Elongases/metabolism
Mice
*Membrane Lipids/metabolism
Acetyltransferases/metabolism
Humans
*Retina/metabolism

@article {pmid42724764,
year = {2026},
author = {Zhang, J and Feng, J and Song, J and Bi, H},
title = {The pathogenesis of müller cell glial-mesenchymal transition in retinal fibrosis-related eye diseases.},
journal = {Frontiers in cell and developmental biology},
volume = {14},
number = {},
pages = {1919772},
pmid = {42724764},
issn = {2296-634X},
abstract = {Retinal fibrosis represents an important pathological feature of several vision-threatening ocular diseases, including advanced diabetic retinopathy and neovascular age-related macular degeneration. Its progression may be associated with reactive changes in Müller glial cells and their acquisition of mesenchymal-like phenotypes. As the predominant glial population in the retina, Müller glial cells play crucial physiological roles in maintaining retinal homeostasis. However, under pathological conditions, they can become reactive and acquire mesenchymal- or myofibroblast-like features through a process referred to as glial-mesenchymal transition (GMT), potentially contributing to fibrotic remodeling. This review systematically examines the molecular mechanisms associated with Müller cell GMT, including the regulatory involvement of the TGF-β and Notch signaling pathways, inflammatory mediators, and oxidative stress. It discusses the potential contribution of GMT to retinal fibrotic progression. Furthermore, this article synthesizes the potential pathological and therapeutic relevance of GMT in related ocular diseases and discusses experimental intervention strategies targeting Müller cell phenotypic remodeling. Understanding the regulatory network of Müller cell GMT may inform the development of future therapeutic approaches to prevent or attenuate retinal fibrosis.},
}

@article {pmid42725097,
year = {2026},
author = {Mazinani, FSH and Ashtiani, MK and Moradmand, A and Satarian, L},
title = {RPE-derived extracellular matrix improves graft retention and photoreceptor preservation in preclinical models of retinal degeneration.},
journal = {Matrix biology plus},
volume = {32},
number = {},
pages = {100203},
pmid = {42725097},
issn = {2590-0285},
abstract = {INTRODUCTION: Human pluripotent stem cells-derived retinal pigment epithelium (hPSC-RPE) represent a promising therapeutic approach for macular degeneration. This study examines whether RPE-derived extracellular matrix (RPE-ECM), enhances survival and functional outcomes following hPSC-RPE suspension transplantation in a preclinical model of retinal degeneration.

METHODS: hPSC-RPE cells were cultured under three conditions: control, RPE-conditioned medium (RPE-CM), and RPE-ECM. In vitro, the cells were assessed for proliferation, monolayer organization, and gene expression. In vivo, GFP-labeled hPSC-RPE cells were co-transplanted with the corresponding treatments into the subretinal space of a mouse model of retinal degeneration. For functional assessment, the cells were injected into RCS rats, with visual acuity tracked over six months using optomotor response testing. Retinal morphometry was analyzed by immunohistology techniques to evaluate graft integration and structural rescue.

RESULTS: In vitro, culture of hPSC-RPE cells with RPE-ECM enhanced proliferation and promoted monolayer formation, and increased Nidogen expression. In vivo, co-transplantation with RPE-ECM significantly improved mice retinal graft integration (47.1% vs. 3.6% in control, P < 0.001) and visual acuity over four months in RCS rats. RPE-derived ECM improved graft retention and photoreceptor preservation observed at 180 days (P < 0.001), with neuroprotective effects extending beyond the graft site to the contralateral retina.

CONCLUSION: These findings suggest that co-transplantation with RPE-ECM enhances the integration and function performance of hPSC-RPE cells and may represent a promising strategy to improve graft viability within the host retina. Nevertheless, this study has several limitations, including short-term assessment in animal models and the lack of detailed ECM compositional analysis. Further studies are required to elucidate the underlying mechanisms and to evaluate the long-term transplantation potential of this approach in clinical settings.},
}

@article {pmid42722145,
year = {2026},
author = {Seol, A and Jeong, JS and Kim, JE and Song, HJ and Lim, SJ and Wang, SH and Ryu, YE and Kim, YR and Yun, W and An, BS and Hwang, DY},
title = {HepG2 cells-derived exosomes exacerbate blue light-induced AMD-like retinal degeneration in A2E-laden ARPE-19 cells and BALB/c mice.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111231},
doi = {10.1016/j.exer.2026.111231},
pmid = {42722145},
issn = {1096-0007},
abstract = {Exosomes derived from hepatic cells have emerged as important mediators of inter-organ communication and may contribute to retinal degeneration associated with age-related macular degeneration (AMD) through the liver-eye axis. However, their role in AMD pathogenesis remains poorly understood. In this study, we investigated whether HepG2 cell-derived exosomes (HG-EX) exacerbate AMD-like retinal degeneration using in vitro and in vivo AMD-mimicking models. ARPE-19 cells co-treated with N-retinylidene-N-retinylethanolamine (A2E) and blue light (BL), as well as BL-exposed BALB/c mice, were pretreated with HG-EX. In AMD-mimicking ARPE-19 cells, HG-EX pretreatment significantly increased intracellular reactive oxygen species (ROS) and nitric oxide (NO) production while suppressing the expression of superoxide dismutase (SOD) and nuclear factor erythroid 2-related factor 2 (Nrf2). In addition, HG-EX altered inflammatory signaling by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, while enhancing inflammasome-related protein expression. Apoptosis-related proteins and pro-angiogenic factors were also markedly elevated following HG-EX treatment. In AMD-mimicking mice, HG-EX administration significantly increased the retinal expression of COX-2, B-cell lymphoma 2 (Bcl-2)/ Bcl-2-associated X protein (Bax), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, accompanied by a reduction in the thickness of the outer segment (OS) and inner nuclear layer (INL). Collectively, these findings demonstrate that HG-EX exacerbate oxidative stress, inflammation, apoptosis, and angiogenesis in both cellular and animal models that recapitulate selected pathological features of AMD. Our results suggest that HG-EX may contribute to AMD-like retinal degeneration and warrant further investigation into their potential role in AMD pathogenesis.},
}

@article {pmid42720425,
year = {2026},
author = {Hua, X and Hormel, TT and Wang, J and Flaxel, CJ and Bailey, ST and Hwang, TS and Jia, Y},
title = {Structural and Angiographic Assessment of the Nerve Fiber Layer in Age-Related Macular Degeneration and Diabetic Retinopathy.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {11},
pages = {17},
doi = {10.1167/iovs.67.11.17},
pmid = {42720425},
issn = {1552-5783},
mesh = {Humans ; Female ; *Diabetic Retinopathy/diagnosis/pathology ; *Nerve Fibers/pathology ; Male ; Aged ; *Fluorescein Angiography/methods ; *Macular Degeneration/diagnosis/pathology ; *Retinal Ganglion Cells/pathology ; Tomography, Optical Coherence/methods ; Middle Aged ; *Retinal Vessels/pathology ; Aged, 80 and over ; *Optic Disk/pathology/blood supply ; },
abstract = {PURPOSE: The purpose of this study was to evaluate structural and microvascular alterations in the nerve fiber layer (NFL) in age-related macular degeneration (AMD) and diabetic retinopathy (DR).

METHODS: A total of 74 healthy controls, 101 patients with AMD, and 117 patients with DR were included. One eye per participant was imaged using a Solix OCTA device centered on the optic disc to measure NFL thickness and nerve fiber layer plexus (NFLP) vessel density (VD). For both parameters, we analyzed the independent associations of age, AMD, and DR; compared age-matched healthy controls with the AMD groups and with the DR groups; and evaluated correlations with age in healthy controls.

RESULTS: Multivariate analyses demonstrated that age was independently associated with both NFL thickness and NFLP VD, whereas AMD was not associated with either parameter and DR was associated only with NFLP VD. The associations of AMD and DR with these two parameters were also confirmed in age-matched analyses. Additionally, NFLP VD decreased significantly with increasing DR severity (P < 0.001). In healthy controls, age was significantly correlated with both NFL thickness (Spearman's ρ = -0.26, P = 0.026) and NFLP VD (ρ = -0.32, P = 0.006).

CONCLUSIONS: NFL thickness was associated with age, but not with AMD or DR. In contrast, DR was independently associated with reduced NFLP VD, which also significantly correlated with DR severity. These findings provide evidence supporting further investigation of NFLP VD in relation to DR, while accounting for age.},
}

Humans
Female
*Diabetic Retinopathy/diagnosis/pathology
*Nerve Fibers/pathology
Male
Aged
*Fluorescein Angiography/methods
*Macular Degeneration/diagnosis/pathology
*Retinal Ganglion Cells/pathology
Tomography, Optical Coherence/methods
Middle Aged
*Retinal Vessels/pathology
Aged, 80 and over
*Optic Disk/pathology/blood supply

@article {pmid42721102,
year = {2026},
author = {Lenhof, S and Mathis, T and Lepretre, N and Rencker, J and Kodjikian, L},
title = {Faricimab in previously treated nAMD: Real-World Outcomes of a No-Loading-Dose Switching Protocol.},
journal = {Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde},
volume = {},
number = {},
pages = {1},
doi = {10.1159/oph/aeeag012},
pmid = {42721102},
issn = {1423-0267},
abstract = {INTRODUCTION: Evaluate efficacy, anatomical outcomes, and safety of switching to faricimab without a loading dose, using a standardized institutional switch protocol, in patients with previously treated neovascular age-related macular degeneration (nAMD) who achieved a maximum fluid-free interval of 8 weeks or less with aflibercept or ranibizumab.

METHODS: Retrospective, single-center cohort study conducted at Croix-Rousse Hospital, Lyon and included eyes with a maximum fluid-free interval of 8 weeks or less on aflibercept or ranibizumab, switched to faricimab between November 2023 and December 2024. Eyes were classified as Poor Responders (PR) or Frequent Flyers (FF) based on their prior anti-VEGF response. No loading dose was administered. Primary outcome was change in last intended treatment interval. Secondary outcomes included best-corrected visual acuity (BCVA), SD-OCT parameters, predictors of interval extension and safety.

RESULTS: 128 eyes were included. Before switching, mean (SD) treatment duration was 36.4 (21.9) months with a mean (SD) 28.2 (17.0) intravitreal injections. After switching, the median gain in the last intended interval was 2.7 [IQR 2.1-3.3] weeks (p<0.001). Subgroup analysis showed a median gain of 3.1 weeks in PR (p<0.001) and 2.4 weeks in FF (p<0.001). BCVA remains stable (p=0.37). Significant reductions were observed in CMT (p<0.001), SHRM (p=0.02), IRF (p<0.001), and SRF (p<0.001). Baseline characteristics were not associated with treatment interval extension. There was one case of anterior uveitis and vitritis, which resolved with topical corticosteroid treatment.

CONCLUSION: In previously treated nAMD patients, switching to faricimab without a loading dose achieved meaningful treatment interval extension, potentially reducing treatment burden without compromising efficacy.},
}

@article {pmid42717802,
year = {2026},
author = {Freeman, WR and Vail, D and Ye, M and López, FJ and Robinson, MR and Huang, J and Hallak, JA},
title = {Real-World Dosing Intervals for Long-Acting Anti-VEGF Intravitreal Injection Therapies in nAMD and DME: Academy IRIS[®] Registry Analysis.},
journal = {Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics},
volume = {},
number = {},
pages = {10807683261484815},
doi = {10.1177/10807683261484815},
pmid = {42717802},
issn = {1557-7732},
abstract = {PURPOSE: To determine real-world dosing intervals for long-acting intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapies in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME).

METHODS: Retrospective observational cohort study in American Academy of Ophthalmology IRIS[®] Registry (Intelligent Research in Sight) patients with nAMD or DME treated with aflibercept 8 mg (aflibercept) or faricimab. Mean injection intervals during a ≤24-month period beginning 3 or 4 months after the initial injection were evaluated and descriptively contrasted with those in phase 3 clinical trials.

RESULTS: The mean dosing interval was 5-8, 9-12, and ≥13 weeks in 27.5%, 45.6%, and 25.8% of aflibercept-treated patients with nAMD (n = 40,065); 27.0%, 43.4%, and 28.3% of aflibercept-treated patients with DME (n = 13,045); 40.5%, 36.1%, and 20.8% of faricimab-treated patients with nAMD (n = 132,697); and 42.2%, 31.7%, and 22.5% of faricimab-treated patients with DME (n = 39,849). Dosing intervals were consistent between treatment-naïve and previously treated patients. In aflibercept phase 3 studies, 77% (nAMD) and 89% (DME) of patients achieved a 16-week dosing interval. In faricimab phase 3 studies, 45% (nAMD) and 52% (DME) of patients achieved a 16-week dosing interval.

CONCLUSION: Extension of injection intervals to 16 weeks is greatly reduced in real-world experience compared with phase 3 clinical studies. This discrepancy could be explained by protocol-mandated restrictive rescue criteria used in the registration studies, allowing injection only after vision loss and significant fluid recurrence. Current longer-acting anti-VEGF medications offer an extension to only 5-12 weeks for most patients in the real world.},
}

@article {pmid42718898,
year = {2026},
author = {Shen, LL and Rosenfeld, PJ and Beqiri, S and O'Brien, RC and Zhang, J and Chew, EY and Del Priore, LV and Stewart, JM},
title = {Intereye Correlation in Bilateral Geographic Atrophy: Morphology and Growth Rates in the Age-Related Eye Disease Study.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101353},
pmid = {42718898},
issn = {2666-9145},
abstract = {PURPOSE: To evaluate intereye correlation in geographic atrophy (GA) lesion morphology, topography, and growth rates, and whether fellow eyes could improve trial efficiency as internal controls.

DESIGN: Secondary analysis of a multicenter, prospective, randomized controlled trial.

PARTICIPANTS: Age-Related Eye Disease Study participants with bilateral GA.

METHODS: Color fundus photographs were used to delineate GA lesions and measure area, perimeter, circularity index, focality, and lesion number. Intereye correlations were evaluated cross-sectionally and longitudinally for 3 GA growth rates (area, square root-transformed, and perimeter-adjusted growth rate). Longitudinal correlations used the first-to-last interval (mean, 5.5 years). Sample-size requirements for paired and unpaired designs were estimated through exploratory power analyses in eyes with 1-year follow-up.

MAIN OUTCOME MEASURES: Geographic atrophy size, morphology, topographic distribution, and growth rate.

RESULTS: In 226 eyes from 113 patients, moderate-to-strong associations were observed between fellow eyes for GA area (ρ = 0.63), perimeter (ρ = 0.69), circularity index (ρ = 0.56), and across all 4 quadrants (range, ρ = 0.51-0.61). Longitudinally, intereye associations were moderate-to-strong for GA area growth rates (ρ = 0.74), square root-transformed area growth rates (ρ = 0.62), and perimeter-adjusted growth rates (ρ = 0.60). These values reflect the first-to-last interval (mean, 5.5 years); over 1 year, correlations were markedly lower (ρ = 0.53, 0.40, 0.34). By baseline lesion size, intereye correlation was slightly higher for area growth rate in small lesions (≤0.9 disc areas [DAs]) but comparable between area- and perimeter-adjusted rates in larger lesions (>0.9 DA). In exploratory 1-year power analyses, a paired design with within-participant randomization of study and fellow eyes was associated with approximately 40% lower estimated sample-size requirements than an unpaired design (149 pairs vs. 250 eyes per arm for area growth rate); adding a perimeter-adjusted endpoint in lesions >0.9 DA reduced the estimate to 50 pairs per arm.

CONCLUSIONS: We observed moderate-to-strong inter-eye correlations in GA morphology, topography, and progression. For exploratory designs of local unilateral therapies, fellow eyes may serve as internal controls alongside square root-transformed or perimeter-adjusted endpoints, reducing sample sizes, particularly for lesions >0.9 DA. Because these analyses use color fundus photography rather than fundus autofluorescence, they are hypothesis-generating for modern trials. These correlations may also inform group-level counseling on fellow-eye progression.

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

@article {pmid42718940,
year = {2026},
author = {Jaffe, GJ and Wykoff, CC and McCaleb, ML and Barrett, TD and Frazer-Abel, A and Norris, D and Luhmann, UFO and Cukras, C and Yin, L and Lomax, M and Fauser, S and Schneider, E and Brice, GT and , },
title = {GOLDEN: Efficacy and Safety of Complement Factor B Antisense, Sefaxersen, in Geographic Atrophy due to Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101340},
pmid = {42718940},
issn = {2666-9145},
abstract = {OBJECTIVE: To evaluate the efficacy and safety of sefaxersen, an investigational antisense oligonucleotide targeting complement factor B (FB), in slowing the progression of geographic atrophy (GA) secondary to age-related macular degeneration (AMD).

DESIGN: Randomized, double-masked, placebo-controlled, adaptive phase II clinical trial.

SUBJECTS: A total of 332 patients with GA secondary to AMD were enrolled, with 91% of treated patients completing the final study visit at 56 weeks.

METHODS: In stage 1, 58 patients received subcutaneous injections of 40, 70, or 100 mg sefaxersen or placebo monthly. An interim analysis for FB, pharmacokinetics, and safety was conducted when patients reached at least 13 weeks of treatment to select 2 doses for expansion. In stage 2, an additional 274 patients were randomized to 40 or 70 mg sefaxersen or placebo. Patients were stratified based on baseline GA size, baseline rate of GA growth, and presence/history of exudative choroidal neovascularization in the fellow eye. Geographic atrophy area was assessed by fundus autofluorescence imaging. Safety assessments included ocular and systemic adverse events, laboratory parameters, and vital signs.

MAIN OUTCOME MEASURES: The primary endpoint was the rate of GA lesion growth from baseline to week 49. Prespecified endpoints included changes from baseline in best-corrected visual acuity, low-luminance visual acuity, systemic complement measures, and occurrence of treatment-related adverse events.

RESULTS: Sefaxersen did not significantly reduce the rate of GA growth versus placebo. Differences in adjusted mean GA rate of growth versus placebo were -0.25 mm[2] (-11.5%, P = 0.171) and -0.08 mm[2] (-3.8%, P = 0.647) for 40 and 70 mg groups, respectively. At steady state, a reduction in adjusted mean plasma FB levels (40 mg: -63% and 70 mg: -69%) led also to a reduction in alternative pathway activity (adjusted mean -22% and -34%, respectively). The safety profile, both ocular and nonocular, of sefaxersen was comparable to that of the placebo, with the most common adverse events being coronavirus disease 2019, urinary tract infections, and nasopharyngitis.

CONCLUSIONS: Sefaxersen reduced systemic FB levels and alternative pathway activity, but the effect on GA growth rate was not significant compared with placebo. The treatment was well tolerated with a safety profile consistent with previous studies.

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

@article {pmid42718944,
year = {2026},
author = {de Vries, VA and Lee, SS and Stuart, KV and Schulze, A and Hunter, ML and Hopf, S and Pfeiffer, N and Lingham, G and Luben, RN and Wang, YX and Haarman, AEG and Tedja, MS and Verhoeven, VJM and Jonas, JB and Schuster, AK and Khawaja, AP and Klaver, CCW and Mackey, DA and Ramdas, WD and , },
title = {A Comprehensive Assessment of the Shared Genetic Architecture between Myopia and Open-Angle Glaucoma.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101328},
pmid = {42718944},
issn = {2666-9145},
abstract = {OBJECTIVE: Individuals with high myopia have an increased prevalence of open-angle glaucoma (OAG). We aim to clarify the possibly shared genetic architecture of myopia and OAG, in particular in high myopes with myopic macular degeneration (MMD), where OAG screening is highly challenging.

DESIGN: Individual participant data meta-analysis of one-sample Mendelian randomization analyses and pleiotropic analysis under a composite null hypothesis.

PARTICIPANTS: A total of 34 825 participants from 6 population-based cohort studies and 1 high myopia case-control study, including 708 OAG and 1953 high-myopia cases.

METHODS: First, we calculated and validated genetic risk scores (GRSs) for OAG and myopia in each cohort. We subsequently meta-analyzed linear and logistic regression models for the association of a myopia GRS with OAG, intraocular pressure (IOP), and vertical cup-to-disc ratio (VCDR), and the association of an OAG-GRS with high myopia, axial length, and spherical equivalent. We stratified the analysis of OAG in different stages of axial elongation, and in high myopes with or without MMD. Pleiotropic analysis under a composite null hypothesis was applied to genome-wide association study summary statistics.

MAIN OUTCOME MEASURES: Odds ratio (OR) of OAG and high myopia, and mean difference in IOP, VCDR, axial length, and spherical equivalent.

RESULTS: One standard deviation (SD) increase in myopia GRS was associated with an OR (95% CI) of 1.18 (1.09, 1.28) for OAG, a beta (95% CI) of 0.04 (0.00, 0.08) mmHg in IOP, and of 0.005 (0.003, 0.007) in VCDR. The OAG-GRS was not significantly associated with high myopia compared to emmetropes, but a 1 SD increase was associated with a beta (95% CI) of 0.05 (0.01, 0.08) mm in axial length and of -0.05 (-0.10, -0.00) diopters in spherical equivalent. One SD increase in OAG-GRS had a substantially larger effect on OAG in high myopes with MMD, with an OR (95% CI) of 3.83 (1.89, 7.78) compared to 1.55 (1.24, 1.94) in emmetropes. Finally, we identified 95 independent pleiotropic single-nucleotide polymorphisms (SNPs).

CONCLUSIONS: There is strong evidence for pleiotropy between myopia and OAG. Further research into the biological mechanisms of the identified pleiotropic SNPs is needed. An OAG-GRS might help to clinically estimate OAG risk, in particular in individuals with MMD.

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

@article {pmid42720289,
year = {2026},
author = {Rani, T and Vyas, M and Rachna, and Sai Charan, L and Vijayasimha, M},
title = {Comment on: Light Adjustable Lens Implantation with Cataract Surgery in Eyes with Macular Pathology.},
journal = {Journal of cataract and refractive surgery},
volume = {},
number = {},
pages = {},
doi = {10.1097/j.jcrs.0000000000002049},
pmid = {42720289},
issn = {1873-4502},
}

@article {pmid42709274,
year = {2026},
author = {Candan, O and Orman, G and Ünlü, N and Uney, G and Acar, DD and Burcu, A},
title = {Pre- and post-COVID-19 changes in retinal disease patterns in Türkiye: insights from a tertiary hospital.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42709274},
issn = {1573-2630},
mesh = {Humans ; *COVID-19/epidemiology ; Retrospective Studies ; Male ; *Tertiary Care Centers/statistics & numerical data ; Middle Aged ; Prevalence ; Female ; Aged ; *Retinal Diseases/epidemiology/diagnosis ; *SARS-CoV-2 ; Adult ; Aged, 80 and over ; },
abstract = {PURPOSE: To estimate the prevalence of common retinal diseases in Türkiye during 2017-2023 and to characterize age and gender-specific differences.

METHODS: This retrospective, single-center, hospital-based study included 475,865 adults presenting to an ophthalmology outpatient clinic. The study period was divided into pre-pandemic (January 2017-March 2020), acute pandemic (March-June 2020), and post-pandemic (June 2020-July 2023) phases. Patient age, gender, diagnoses, and major complications were recorded. The primary outcomes were defined as changes in the prevalence of common retinal diseases and their complications before and after the pandemic.

RESULTS: Among 475,865 adults, 10,131 (2.13%) were diagnosed with a retinal disease. Age-related macular degeneration was the most prevalent disease, with prevalence increasing from 0.99% in the pre-pandemic period to 1.23% in the post-pandemic period (P < .001). Diabetic retinopathy was the second most common and remained stable across the pandemic periods (0.95% and 0.97%; P = .395). Diabetic macular edema (DME) exhibited a notable increase, particularly among patients aged ≥ 50 years (from 16.68 to 26.72%; P < .001). Retinal vein occlusion (RVO) ranked third, with prevalence rising from 0.17% before the pandemic to 0.25% after (P < .001). The proportion of patients with DME secondary to RVO requiring injection increased from 38.2% in the pre-pandemic period to 43.8% in the post-pandemic period.

CONCLUSION: This large-scale longitudinal study demonstrated significant changes in the epidemiology of several retinal diseases across the pre- and post-pandemic periods in Türkiye. However, the mechanisms underlying these changes remain uncertain and need to be clarified through future multicenter population-based studies.},
}

Humans
*COVID-19/epidemiology
Retrospective Studies
Male
*Tertiary Care Centers/statistics & numerical data
Middle Aged
Prevalence
Female
Aged
*Retinal Diseases/epidemiology/diagnosis
*SARS-CoV-2
Adult
Aged, 80 and over

@article {pmid42709378,
year = {2026},
author = {Yang, X and Zhang, S and Wang, Y and Shi, J and Li, W and Lou, X and Yu, Y and Zhang, J and Sang, A},
title = {LAPTM5 correlates with RPE senescence and subretinal fibrosis through the LAPTM5-WWP2-OPTN mitophagy cascade and cGAS/STING activation in a D-galactose-induced aging model.},
journal = {GeroScience},
volume = {},
number = {},
pages = {},
pmid = {42709378},
issn = {2509-2723},
support = {M2024045//Jiangsu Commission of Health/ ; K2024063//Jiangsu Commission of Health/ ; LKM2024040//Jiangsu Commission of Health/ ; MS2025005//Nantong Municipal Commission of Health and Family Planning/ ; 23ZH313//Nantong University/ ; },
abstract = {Retinal pigment epithelium (RPE) senescence acts as a core driver of subretinal fibrosis, a major irreversible pathological feature that exacerbates age-related macular degeneration (AMD). Mitophagy is essential for maintaining RPE homeostasis during aging. However, the upstream molecular mechanisms underlying mitophagy impairment in senescent RPE remain poorly defined. Here, we show that lysosomal-associated transmembrane protein 5 (LAPTM5) is significantly upregulated in human AMD specimens and D-galactose (D-gal)-induced aging mouse model, with its overexpression correlating with transcriptomic signatures of RPE senescence and fibrogenesis. Gain- and loss-of-function assays validate that LAPTM5 acts as an important regulator of RPE senescence and senescence-associated secretory phenotype (SASP) production. Mechanistically, LAPTM5 physically interacts with and promotes the lysosome-dependent degradation of WW domain-containing E3 ubiquitin protein ligase 2 (WWP2), which in turn diminishes optineurin (OPTN) polyubiquitination and ablates OPTN-mediated mitophagy. The resulting mitophagy deficiency is associated with cytoplasmic mitochondrial DNA leakage and sustained cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) innate immune activation, stimulating robust senescence-associated secretory phenotype (SASP) release that promotes RPE epithelial-mesenchymal transition (EMT) and exacerbates subretinal fibrotic scarring. Notably, AAV-mediated RPE-specific Laptm5 knockdown efficiently alleviates subretinal fibrotic lesions in the aged mouse model, while pharmacological STING inhibition with H-151 markedly attenuates EMT progression. Collectively, our findings identify a previously uncharacterized LAPTM5-WWP2-OPTN mitophagy cascade and reveal a new pathogenic circuit linking impaired mitophagy to RPE senescence and age-related retinal fibrosis, offering translational prospects for treating senescence-associated fibrotic diseases.},
}

@article {pmid42709406,
year = {2026},
author = {Macchione, RM and Ottaiano-Poli, PA and Germano-Morrel, CS and Tomishige, KS and Kasahara, N},
title = {Vision-related quality of life in glaucoma and age-related macular degeneration patients from a middle-income country.},
journal = {International health},
volume = {},
number = {},
pages = {},
doi = {10.1093/inthealth/ihag089},
pmid = {42709406},
issn = {1876-3405},
support = {//ARVO/ ; },
abstract = {BACKGROUND: Vision-related quality of life (VRQoL)-vision's impact on one's social, emotional and economic well-being-has not been extensively studied in patients living in middle-income countries. The aim of this study was to compare the VRQoL among age-related macular degeneration (AMD), primary open-angle glaucoma (POAG) and normal subjects in Brazil.

METHODS: This was a case-control, cross-sectional study. Patients with AMD or POAG and normal controls underwent a complete eye examination; all participants answered the Brazilian-Portuguese version of the Visual Function Questionnaire 25 (VFQ-25). Each item was scored and an overall composite score was calculated and compared among groups with an analysis of variance test.

RESULTS: The sample included 60 patients with AMD, 64 with POAG and 60 controls. All groups were matched for age, gender, ethnic distribution and comorbidities. The VFQ-25 total score was lower in both AMD (50.6±20.9) and POAG (61.8±20.4) as compared with controls (89.2±9.1, p<0.001); scores for AMD patients were lower than for POAG patients (p<0.001).

CONCLUSIONS: Brazilian patients with POAG, and especially AMD, presented significantly lower VRQoL scores, underscoring the need to improve the care of patients with visual impairment in Brazil.},
}

@article {pmid42709964,
year = {2026},
author = {Wu, Y and Fu, DJ and Zhou, Y and Wagner, SK and Keane, PA},
title = {Performance, Failures, and Oversight of a Large Language Model Agent for Clinical Data Analysis: Evaluation Study.},
journal = {Journal of medical Internet research},
volume = {28},
number = {},
pages = {e99597},
pmid = {42709964},
issn = {1438-8871},
mesh = {*Large Language Models ; Humans ; *Data Analysis ; },
abstract = {BACKGROUND: Large language model (LLM) agents capable of generating and executing statistical code from natural language may broaden access to clinical data analysis, yet which pipeline stages they perform reliably and which require expert oversight remain poorly defined.

OBJECTIVE: This study aimed to evaluate the performance and systematic failure modes of an LLM agent across 5 stages of a clinical data analysis workflow.

METHODS: The publicly available dataset and R script (R Foundation for Statistical Computing) were drawn from a previously published study of 12-year outcomes in 7802 patients with eyes with neovascular age-related macular degeneration at Moorfields Eye Hospital. Participants were evaluated using an LLM agent (Claude; Anthropic) across 3 interaction modes (Chat, Code, and Cowork). It was asked to perform 3 levels of data analysis practice: prompt A, to generate research questions from raw data only; prompt B, to develop a statistical analysis plan (SAP) from a high-level clinical objective, then execute it; and prompt C, to execute an analysis given an investigator-drafted SAP. Each was replicated 3 times (27 total runs). Qualitative evaluation of research question thematic coverage (prompt A), SAP completeness against a reference checklist (prompt B), and evaluation of execution outputs against validated reference values and of result text and narrative summaries against execution logs (prompts B and C) was conducted.

RESULTS: The agent generated 18 clinically grounded questions spanning 7 domains; Cowork mode uniquely reached 3 thematic areas requiring data-driven methods. All 9 SAPs correctly identified the statistical framework. Kaplan-Meier estimates were near-identical across 17 completed runs. Systematic execution errors emerged: SAP quality did not predict code correctness, and within-mode errors propagated identically across independent repetitions. Result text accurately reflected execution logs in nearly all runs, though unit propagation and an undisclosed postcrash rerun were identified. Of 17 narrative summaries, 8 were fully satisfactory; 2 runs produced clinically meaningful errors.

CONCLUSIONS: LLM agents perform reliably for question generation and SAP drafting but require expert verification of formula composition, cohort boundary logic, and concordance computation before results are reported. Using an ophthalmology dataset as a controlled testbed, this study develops and applies an evaluation framework whose lessons are likely applicable across clinical specialties.},
}

*Large Language Models
Humans
*Data Analysis

@article {pmid42712725,
year = {2026},
author = {Long, N and Si, M and Jiang, Y and Chen, F and Chen, B and Jiang, F and Pan, S and Chu, X and Wu, H},
title = {Bionic vision technologies: progress and perspectives on retinal prostheses and optogenetics for the treatment of advanced retinal degeneration.},
journal = {Frontiers in medical technology},
volume = {8},
number = {},
pages = {1898982},
pmid = {42712725},
issn = {2673-3129},
abstract = {Advanced degenerative retinal diseases [e.g., retinitis pigmentosa (RP) and age-related macular degeneration (AMD)] are characterized by irreversible photoreceptor loss, and conventional interventions rarely prevent progression to profound vision loss at advanced stages. Retinal prostheses and optogenetic therapies are two leading bionic strategies to bypass absent photoreceptors, yet both are limited by a shared "encoding-biointerface" bottleneck: converting external scenes into interpretable neural activity in surviving retinal circuits with adequate selectivity, safety margins, and long-term stability. This review critically compares the two approaches in spatial resolution, neural adaptation, and biosafety, while explicitly distinguishing clinical evidence from preclinical and proof-of-concept studies. Retinal prostheses provide near-term light perception and limited form vision but are constrained by current spread, non-selective pathway/axon recruitment, interface reactions, and cortical decoding burden. Optogenetic restoration offers cell-type-biased reactivation and potentially more physiological processing, but currently remains coupled to external light-delivery hardware and is limited by scattering, heterogeneous transduction, safety-limited irradiance, restricted dynamic range, and adeno-associated virus (AAV)-related inflammatory risk. We highlight emerging integrative directions, including opto-electronic hybrid interfaces, adaptive encoding, broadband subretinal nanomaterial-based photovoltaic nanoprostheses, and experimental acoustic modalities (e.g., focused ultrasound and sonogenetics), alongside ethical and accessibility considerations for translation.},
}

@article {pmid42713229,
year = {2026},
author = {Ho, SC and Lee, IXY and Liu, C and Yu, M and Tan, HC and Tan, GSW and Liu, YC},
title = {Fenofibrate in ophthalmology: therapeutic efficacy and mechanisms.},
journal = {Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques},
volume = {29},
number = {},
pages = {16995},
pmid = {42713229},
issn = {1482-1826},
mesh = {Humans ; *Fenofibrate/therapeutic use/pharmacology/administration & dosage ; Animals ; *Eye Diseases/drug therapy/metabolism ; *Hypolipidemic Agents/pharmacology/therapeutic use/administration & dosage ; PPAR alpha/agonists/metabolism ; },
abstract = {Ophthalmic diseases are a growing global cause of visual impairment, driven by population aging and the rising prevalence of diabetes mellitus. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist widely used for dyslipidemia, has emerged as a candidate for therapeutic repurposing in ophthalmology. This narrative review synthesizes current preclinical and clinical evidence on fenofibrate across anterior and posterior segment diseases, including diabetic corneal neuropathy, diabetic keratopathy, dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, diabetic retinopathy, diabetic macular edema, neovascular age-related macular degeneration, and central retinal artery occlusion. Across ocular disease models, fenofibrate demonstrates neuroprotective, vascular stabilizing, and tissue-remodeling effects. These actions appear to involve modulation of shared pathogenic pathways, including PPARα-dependentregulation of inflammatory signaling, mitochondrial and lipid metabolism, and preservation of epithelial, endothelial, neuronal, and vascular integrity. Clinical evidence is strongest for diabetic retinopathy, where randomized trials support a potential adjunctive role in slowing progression and reducing interventions in patients with early-to-moderate disease. Preliminary clinical evidence for diabetic corneal neuropathy is promising but limited, whereas data for dry eye disease, corneal burns, Fuchs endothelial corneal dystrophy, neovascular age-related macular degeneration, and retinal ischemic injury remains preclinical. Emerging experimental ocular delivery strategies may improve local bioavailability while reducing systemic exposure. Overall, fenofibrate represents a biologically plausible adjunctive ophthalmic therapy, but further randomized trials, mechanistic studies, pharmacokinetic evaluation, and long-term safety assessments are required to define its therapeutic role beyond diabetic retinopathy.},
}

Humans
*Fenofibrate/therapeutic use/pharmacology/administration & dosage
Animals
*Eye Diseases/drug therapy/metabolism
*Hypolipidemic Agents/pharmacology/therapeutic use/administration & dosage
PPAR alpha/agonists/metabolism

@article {pmid42714580,
year = {2026},
author = {Hoffmann, S and Liegl, C and Stasik, I and Holz, FG and Liegl, R},
title = {One-year real-world data of intravitreal faricimab in patients with pre-treated neovascular age-related macular degeneration.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42714580},
issn = {1435-702X},
abstract = {PURPOSE: To assess one-year real-world outcomes of faricimab therapy in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF agents and managed using a treat-and-extend (TAE) regimen.

METHODS: Patients with treatment-resistant nAMD were switched to faricimab. Functional and structural parameters, including best-corrected visual acuity (BCVA in logMAR), foveal centre point (FCP in µm), central subfield retinal thickness (CSRT in µm), and macular volume (MV in mm³), were recorded over a one-year observation period.

RESULTS: Seventy eyes from 59 patients initiated faricimab therapy between September and December 2022; complete one-year data were available for 60 eyes, with a mean follow-up of 391 ± 20 days. Prior to switching, patients had received an average of 42.4 ± 25.2 anti-VEGF injections over 70.8 ± 45.4 months. Significant structural improvements were observed: FCP decreased from 359 ± 165 μm to 283 ± 132 μm, CSRT from 414 ± 153 μm to 343 ± 116 μm, and macular volume from 2.74 ± 0.67 mm³ to 2.46 ± 0.49 mm³ (all p < 0.001). The mean injection interval increased from 5.8 ± 1.8 weeks to 8.2 ± 3.3 weeks (p < 0.001), indicating improved disease control. BCVA remained stable (0.45 ± 0.37 logMAR vs. 0.44 ± 0.39 logMAR; p = 0.35). At the end of follow-up, 37% of eyes achieved a completely dry macula with no residual intra-, subretinal, or sub-RPE fluid. Two eyes developed mild anterior chamber inflammation, which resolved fully under topical corticosteroids.

CONCLUSION: Switching to faricimab in recalcitrant, heavily pretreated nAMD may yield meaningful structural improvements while stabilizing visual acuity.},
}

@article {pmid42714745,
year = {2026},
author = {Sugisawa, T and Nishi, Y and Imaizumi, H and Aoki, S and Miki, A and Kishi, M and Yamauchi, T and Nagasato, D and Ozawa, Y and Haruta, M and Kato, N and Matsubara, H and Yasukawa, T and Kato, A and Terasaki, H and Hirano, T and Iesato, Y and Tsujinaka, H and Murakami, T and Mitamura, Y and Wakuta, M and Kimura, K and Shimura, M and Gomi, F},
title = {Changes in demographics and treatment trends in neovascular age-related macular degeneration during the COVID-19 pandemic in Japan.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42714745},
issn = {1613-2246},
abstract = {PURPOSE: To elucidate changes in the management of neovascular age-related macular degeneration (nAMD) in Japan during the COVID-19 pandemic .

STUDY DESIGN: Retrospective cohort study.

METHODS: We conducted a multicenter retrospective cohort study of patients newly examined at 16 retina specialist facilities from January 2017 to March 2021. Baseline findings and 3-year follow-up data were compared between pre-pandemic (2017-February 2020) and post-pandemic (March 2020-March 2021) groups.

RESULTS: Analysis of 2271 patients with nAMD revealed a significant decrease in the number of patients examined at hospitals during the COVID-19 pandemic period (p = 0.011), along with a higher proportion of patients who had received treatment within the previous year at local clinics. Baseline ocular findings showed no significant differences between the pre- and post-pandemic groups. Loss to follow-up increased through the second year of the pandemic period (first year, p = 0.0012; second year, p = 0.023). No significant differences were observed during follow-up in visual acuity, central retinal thickness, or number of anti-vascular endothelial growth factor injections. However, in the post-pandemic period the frequency of photodynamic therapy tended to decrease, and examination visits decreased significantly (p = 0.0038).

CONCLUSION: The number of nAMD patients treated in hospitals was lower in the post-pandemic period, and the proportion managed initially in local clinics increased. Although baseline and follow-up characteristics remained largely similar, the use of photodynamic therapy and the number of follow-up visits declined. These findings suggest a shift in the initial nAMD management from hospitals to local clinics during the early post-pandemic period.},
}

@article {pmid42562649,
year = {2026},
author = {Demirayak, P and Fleming, LL and Stewart, P and Chua, R and Visscher, KM},
title = {Increased Attentive Use Is Linked to More Idiosyncratic Functional Connections.},
journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience},
volume = {46},
number = {36},
pages = {},
doi = {10.1523/JNEUROSCI.2178-25.2026},
pmid = {42562649},
issn = {1529-2401},
mesh = {Humans ; Female ; Male ; *Attention/physiology ; Adult ; Magnetic Resonance Imaging ; *Nerve Net/physiology/diagnostic imaging ; *Brain/physiology/diagnostic imaging ; Middle Aged ; Brain Mapping ; },
abstract = {Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brain's complexity, multiple network changes could each move the system toward optimality. Standard approaches examine each connection independently; these studies have often shown considerable interindividual variability and modest effects (Marek et al., 2022). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how "idiosyncratic" the pattern is. We examined how the idiosyncrasy of whole-brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (who use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person to person in healthy vision controls (14 females, 9 males). In a second set of analyses, we examined the brains of people with central vision loss (11 females, 10 males) who use a portion of peripheral vision [the preferred retinal locus (PRL)] more frequently for attention-demanding tasks in their daily lives. The cortical representation of the PRL exhibits more idiosyncratic connections, compared with a control brain region or compared with the same brain region in matched healthy vision controls. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole-brain connections.},
}

Humans
Female
Male
*Attention/physiology
Adult
Magnetic Resonance Imaging
*Nerve Net/physiology/diagnostic imaging
*Brain/physiology/diagnostic imaging
Middle Aged
Brain Mapping

@article {pmid42705516,
year = {2026},
author = {Kim, M and Park, Y and Choi, SW and Lee, EK and Park, UC and Park, KH and Yoon, CK},
title = {Reticular Pseudodrusen Subtypes and Their Interaction With Soft Drusen: Longitudinal Structure-Function Analysis.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.08.047},
pmid = {42705516},
issn = {1879-1891},
abstract = {PURPOSE: To evaluate longitudinal structure-function relationships of reticular pseudodrusen (RPD) subtypes and their interaction with soft drusen (SD) on retinal sensitivity (RS) in intermediate age-related macular degeneration (AMD).

DESIGN: Retrospective cohort study.

SUBJECTS: Forty-six eyes of 28 patients diagnosed with intermediate AMD or RPD who underwent microperimetry at two time points 6 to 12 months apart.

METHODS: RPD presence and subtype (dot or ribbon) and SD were assessed individually at each of 37 Early Treatment Diabetic Retinopathy Study grid test points on co-registered multimodal imaging. Linear mixed-effects models estimated baseline RS and its change by drusen composition, with test-point location as a fixed effect and adjustment for clinical covariates, plus baseline RS for the change analysis.

MAIN OUTCOME MEASURES: Change in RS over follow-up and baseline RS, according to drusen composition.

RESULTS: At baseline, ribbon-type RPD regions showed lower RS than lesion-free regions (mean difference 0.72 ± 0.24 dB, P = .002), whereas dot-type RPD did not differ (P = .120); SD was independently associated with reduced RS (P = .021). No baseline RPD subtype × SD interaction was observed. Longitudinally, a significant interaction was found (P = .005): regions with both ribbon-type RPD and SD showed the greatest RS decline, whereas RPD subtypes did not differ without SD (all P > .9).

CONCLUSIONS: The functional impact of RPD varies by subtype and coexistence with SD. Ribbon-type RPD is associated with greater RS impairment, particularly when combined with SD, highlighting the importance of lesion phenotype in functional risk assessment.},
}

@article {pmid42706530,
year = {2026},
author = {Ranabhat, S and Shakya, K and Bajgai, P and Singh, L and Shrestha, S and Agrawal, R},
title = {Retinal and choroidal morphometric analysis in fellow eye of unilateral wet age related macular degeneration using optical coherence tomography angiography.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42706530},
issn = {1471-2415},
mesh = {Humans ; Male ; *Tomography, Optical Coherence/methods ; *Choroid/blood supply/pathology ; Cross-Sectional Studies ; Female ; *Fluorescein Angiography/methods ; Aged, 80 and over ; *Retinal Vessels/pathology/diagnostic imaging ; Aged ; *Wet Macular Degeneration/diagnosis/pathology/diagnostic imaging ; Middle Aged ; Fundus Oculi ; Visual Acuity ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) when associated with macular neovascularization can cause severe visual morbidity. This study aims to evaluate the retinal and choroidal microvascular alterations using optical coherence tomography angiography (OCTA) in eyes with unilateral wet age-related macular degeneration (AMD) termed as "affected eye" (AE) and compare it with their "fellow eyes" (FE).

METHODS: This cross-sectional study included 60 patients (120 eyes) with age over 50 years. Vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) in the superficial capillary plexuses (SCP), deep capillary plexus (DCP) and avascular slab were assessed using OCTA. Enhanced depth imaging was used to evaluate subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI).

RESULTS: The mean age was 73.9 ± 9.54 years (51-89 years) with 51.7% male. Quantitative OCTA analysis showed no significant inter-eye differences in VD or PD in SCP or DCP (p > 0.05). However, FAZ was significantly enlarged in AE compared with FE in SCP (0.91 ± 0.40 vs. 0.64 ± 0.20 mm²; p < 0.001) and DCP (p < 0.001). FAZ enlargement in the avascular slab was not statistically significant (p 0.20). Pattern I macular neovascularization (MNV) was significantly associated with the shape (p 0.026), presence of anastomoses (p 0.029), and overall activity scores (p 0.001). Inter-eye differences choroidal parameters were statistically significant for SFCT (p 0.019), haller layer (p 0.014) and CVI (p < 0.001). AE status was significantly associated with age (p 0.04) smoking (p 0.01), and lens status (p 0.05).

CONCLUSION: FAZ enlargement demonstrated greater inter-eye separation and higher discriminatory performance compared than density-based OCTA parameters and may reflect localized microvascular or structural alteration in unilateral neovascular AMD. OCTA-based assessment of FE may aid in detecting early microvascular alterations and guiding timely intervention, which may be potentiated by retinal and choroidal vascular or structural remodeling.},
}

Humans
Male
*Tomography, Optical Coherence/methods
*Choroid/blood supply/pathology
Cross-Sectional Studies
Female
*Fluorescein Angiography/methods
Aged, 80 and over
*Retinal Vessels/pathology/diagnostic imaging
Aged
*Wet Macular Degeneration/diagnosis/pathology/diagnostic imaging
Middle Aged
Fundus Oculi
Visual Acuity

@article {pmid42709011,
year = {2026},
author = {Blix, T and Løkken, JFT and Steffensen, LA and Sæther, EM and Husum, YS and Ødegaard, EM and Bragadottir, R and Moe, MC and Jørstad, ØK},
title = {Impact of faricimab and high-dose aflibercept on treatment demand in a tertiary ophthalmic centre in Norway.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70240},
pmid = {42709011},
issn = {1755-3768},
abstract = {PURPOSE: To evaluate the impact of introducing faricimab and high-dose aflibercept on intravitreal injection (IVI) demand and treatment costs for retinal diseases in a large tertiary retina centre.

METHODS: This retrospective longitudinal registry study included all anti-VEGF treatment episodes at Oslo University Hospital, Norway, between 2021 and 2025. Annual injection volumes, treatment patterns, and costs were assessed following the introduction of faricimab (2023) and high-dose aflibercept (2025). High-dose aflibercept was generally administered at 50 μL (5.7 mg). Costs components were estimated using a health-economic model.

RESULTS: A total of 142 960 treatment episodes comprising 169 700 IVIs in 7865 patients (mean age 75.5 years, 56.6% female) were included. Macular degeneration was the most common diagnosis. Treated patients increased from 4148 in 2021 to 4982 in 2025. Injections increased from 31 780 in 2021 to a peak of 35 508 in 2024 before declining to 33 696 in 2025, while mean injections per patient decreased from 7.7 to 6.8. Following its introduction in 2023, faricimab became the most used agent. Off-label bevacizumab proportion decreased from 50.6% in 2021 to 30.0% in 2025. Mean treatment cost per patient increased from NOK 38029 in 2021 to NOK 40187 in 2025 (+5.7%), while total treatment costs increased from NOK 158 million to NOK 200 million (+26.9%).

CONCLUSIONS: The introduction of faricimab and high-dose aflibercept was associated with reduced per-patient treatment intensity, while the treated population continued to increase. Longer-acting anti-VEGF drugs may reduce pressure on retinal services by lowering injection frequency; however, their introduction was associated with higher overall costs.},
}

@article {pmid42698447,
year = {2026},
author = {Wan, Z and Chen, X and Gao, F and Shi, F and Dai, R and Peng, Q and Wei, Q},
title = {Faricimab in neovascular age-related macular degeneration: aqueous humor cytokine profiling and biomarker correlations.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1927909},
pmid = {42698447},
issn = {2296-858X},
abstract = {PURPOSE: To investigate aqueous humor cytokine profile changes in neovascular age-related macular degeneration (nAMD) patients before and after intravitreal faricimab injection, and their correlation with biomarkers.

METHODS: Twenty-three nAMD patients and 10 cataract controls were enrolled. Aqueous humor was collected from nAMD patients at baseline and 12 weeks post-faricimab injection, and from controls during phacoemulsification. Twelve cytokines were quantified via multiplex bead-based immunoassay. OCTA measured central macular thickness (CMT) and retinal vessel density in nAMD eyes.

RESULTS: Baseline vascular endothelial growth factor (VEGF), Angiopoietin-2 (Ang-2) and HGF levels were higher in nAMD patients than controls. Post-treatment, VEGF and Ang-2 decreased below control levels, while hepatocyte growth factor (HGF) and interferon gamma protein 10 (IP-10) increased significantly. Reductions in Ang-2/VEGF correlated positively with decreased CMT and whole retinal thickness, with concurrent improvements in best-corrected visual acuity. Elevated IP-10 showed a correlative association with reduced superficial foveal vessel density.

CONCLUSION: Faricimab dual-blockades VEGF/Ang-2, reducing their aqueous levels, improving CMT/whole retinal thickness and visual acuity. However, post-treatment HGF/IP-10 upregulation indicates compensatory inflammatory-angiogenic remodeling. IP-10 may serve as a potential correlative biomarker linked to subclinical capillary rarefaction. Future studies should explore combined anti-IP-10 therapy or extended dosing intervals to preserve foveal vasculature while maintaining anti-leakage efficacy.},
}

@article {pmid42698711,
year = {2026},
author = {Liu, Y and Li, Z and Ma, Y and Liu, Y},
title = {Targeting angiogenesis: advances in the design and engineered applications of nanobodies.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1912560},
pmid = {42698711},
issn = {1664-3224},
mesh = {Humans ; *Single-Domain Antibodies/therapeutic use/immunology/genetics/chemistry ; Animals ; *Neovascularization, Pathologic/immunology/drug therapy ; Neoplasms/immunology/therapy ; Protein Engineering ; *Angiogenesis Inhibitors/therapeutic use ; },
abstract = {Angiogenesis is a fundamental physiological process; however, its pathological dysregulation drives diseases such as solid tumors, wet age-related macular degeneration, and rheumatoid arthritis. Although clinically effective, conventional anti-angiogenic monoclonal antibodies are limited by poor tissue penetration, off-target toxicities, and susceptibility to compensatory resistance. This review systematically examines the structural advantages and engineering strategies of nanobodies (Nbs) targeting angiogenesis-related pathways. Advanced engineering approaches, such as AI-assisted humanization and multivalent assembly, effectively mitigate immunogenicity and extend serum half-life. Furthermore, multispecific designs can simultaneously block compensatory pathways to circumvent resistance. Moreover, preclinical studies indicate that integrating these molecules into site-specific nanobody-drug conjugates and targeted delivery vehicles may improve therapeutic precision and local drug accumulation; however, their long-term safety, manufacturability, and clinical benefit remain to be established. Functionalizing Nbs with radionuclides or fluorophores may enable the development of novel theranostic platforms that support real-time molecular imaging and image-guided surgery. In parallel, nanobody-based CAR-T (Nb-CAR-T) cells facilitate the targeted remodeling of the disease microenvironment. Ultimately, this review highlights the value of engineered Nbs as a highly programmable and transformative platform. By overcoming key limitations of conventional antibodies, engineered nanobodies open new avenues for precise, multi-dimensional interventions in solid tumors. Their potential in certain non-neoplastic angiogenic diseases is emerging but requires further validation.},
}

Humans
*Single-Domain Antibodies/therapeutic use/immunology/genetics/chemistry
Animals
*Neovascularization, Pathologic/immunology/drug therapy
Neoplasms/immunology/therapy
Protein Engineering
*Angiogenesis Inhibitors/therapeutic use

@article {pmid42700909,
year = {2026},
author = {Zhang, X and Lin, Y and Cheng, J and Yan, M and Huang, Z and Ye, Y and Song, Y},
title = {Association Between Subretinal Hyperreflective Material and OCTA-Derived Macular Neovascularization Morphology in Treatment-Naive Neovascular Age-Related Macular Degeneration.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105645},
doi = {10.1016/j.pdpdt.2026.105645},
pmid = {42700909},
issn = {1873-1597},
abstract = {PURPOSE: To evaluate whether baseline subretinal hyperreflective material (SHRM) status is associated with optical coherence tomography angiography (OCTA)-derived macular neovascularization (MNV) vessel density, complexity, and ramification in treatment-naive neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective, single-center, cross-sectional imaging study included 89 eyes from 89 treatment-naive patients with nAMD. One eye per patient was included to avoid inter-eye correlation. SHRM was assessed on baseline structural optical coherence tomography (OCT). OCTA images were acquired using 6 × 6 mm scans, and MNV lesions were manually delineated as regions of interest. The primary OCTA-derived parameters were MNV vessel density, fractal dimension, and branch points. Multivariable linear regression models were adjusted for age, sex, central macular thickness, and MNV type.

RESULTS: SHRM was present in 56 eyes (62.9%) and absent in 33 eyes (37.1%). Compared with SHRM-negative eyes, SHRM-positive eyes had worse baseline best-corrected visual acuity (BCVA) (P < 0.001), greater central macular thickness (P < 0.001), and higher frequencies of subretinal fluid, intraretinal fluid, and retinal hemorrhage. SHRM-positive eyes also showed higher MNV vessel density (0.262 vs. 0.196; P = 0.017), fractal dimension (1.568 vs. 1.487; P = 0.024), and branch points (140.5 vs. 91.0; P = 0.035). After adjustment, SHRM remained associated with higher MNV vessel density (β = 0.045; P = 0.042), fractal dimension (β = 0.077; P = 0.029), and branch points (β = 98.74; P = 0.045).

CONCLUSIONS: These findings suggest that SHRM-positive status is associated with a denser, more complex, and more ramified OCTA-derived MNV vascular phenotype at baseline in treatment-naive nAMD.},
}

@article {pmid42701791,
year = {2026},
author = {Chen, Z and Liu, J and Cheng, S and Xu, Q},
title = {The Evolving Burden of Age-Related Macular Degeneration in China (1990-2023): Insights from an Aging Society and the Anti-VEGF Era.},
journal = {Clinical epidemiology},
volume = {18},
number = {},
pages = {621990},
pmid = {42701791},
issn = {1179-1349},
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision loss in the elderly. China bears the world's largest AMD burden. This study analyzes the evolving AMD burden in China (1990-2023) and the impact of anti-VEGF therapy.

METHODS: We analyzed data from the Global Burden of Disease (GBD) 2023 study using joinpoint regression, decomposition analysis, and Bayesian modeling. A supplementary meta-analysis of single-arm studies was conducted to assess anti-VEGF efficacy in Chinese patients.

RESULTS: From 1990 to 2023, China's age-standardized prevalence rate (ASPR) and disability-adjusted life year rate (ASDR) for AMD decreased by -0.67% and -1.48% annually, respectively. In 2023, China accounted for 35.82% of global cases and 30.25% of global DALYs. A supplementary meta-analysis of 13 single-arm observational studies showed a pooled efficacy rate of 74% for anti-VEGF drugs in China, albeit with substantial heterogeneity (I[2] = 93.07%), warranting cautious interpretation. The accelerated decline in ASDR after 2011 coincided temporally with the clinical introduction and subsequent insurance coverage of anti-VEGF therapy. Projections indicate a continued decline in burden through 2038.

CONCLUSION: Despite a declining age-standardized burden, China's absolute AMD burden remains substantial due to rapid population aging and other challenges. The temporal association between anti-VEGF therapy availability and the accelerated burden decline suggests a potential contribution of this treatment, though causality cannot be directly inferred from this ecological analysis. The observed trends likely reflect multiple factors, including improved healthcare access, early diagnosis, socioeconomic development, and anti-VEGF therapy. Comprehensive strategies focusing on prevention and equitable healthcare access are needed.},
}

@article {pmid42703379,
year = {2026},
author = {Zeaiter, M and Jaber, H and Gharbi, K and Fernandes, SMB and Mchaik, J and Ahmed, M and Hassan, A and Hammoud, AA},
title = {Faricimab in the Treatment of Retinal Disease: A Narrative Review.},
journal = {Cureus},
volume = {18},
number = {8},
pages = {e114098},
pmid = {42703379},
issn = {2168-8184},
abstract = {Retinal and choroidal diseases, including diabetic macular edema, neovascular age-related macular degeneration, retinal vein occlusion, and polypoidal choroidal vasculopathy, remain a significant cause of visual impairment around the world, especially among elderly . Although anti-vascular endothelial growth factor (anti-VEGF) therapy remains the standard of care, it is limited by its side effect profile, resistance, and high injection burden. This underscores the need for a more optimal and possible replacement. Faricimab is an emerging bispecific antibody targeting VEGF-A and angiopoietin-2, addressing both angiogenesis and vascular permeability by modulating the tyrosine kinase with immunoglobulin-like domains-2 pathway. This literature review synthesizes information from preclinical studies and randomized controlled trials. It focuses on the molecular reasoning behind the use of faricimab and the safety profile compared with anti-VEGF monotherapy.},
}

@article {pmid42705337,
year = {2026},
author = {Kim, DE and Kim, M and Im, M},
title = {Perceptual characteristics of scotomas modulate visual performance under simulated prosthetic vision.},
journal = {Journal of neural engineering},
volume = {},
number = {},
pages = {},
doi = {10.1088/1741-2552/aea36b},
pmid = {42705337},
issn = {1741-2552},
abstract = {Retinal prostheses aim to restore vision in patients blinded by photoreceptor degeneration, yet functional outcomes vary substantially across individuals. Scotomas-regions of reduced or absent visual sensitivity-are a defining feature of retinal degenerative diseases, but their perceptual status is often underappreciated in the design and evaluation of prosthetic vision. Here, we investigated how differences in scotoma perception influence perceptual visual task performance and perceptual representations. Approach. Psychophysical experiments were conducted using a virtual reality (VR) platform that simulated visual field deficits characteristic of retinal degeneration, including age-related macular degeneration (AMD). Two different scotoma conditions, perceptually filled-in (invisible) and solid black, were implemented in a head-mounted display (HMD) environment developed in Unity 3D Game Engine. Participants performed visual tasks while behavioral measures, including accuracy, response time, and eye-tracking metrics, were recorded and analyzed. Main Results. Despite identical visual inputs, task performance showed statistically significant differences depending on the perceptual characteristics (i.e., background-matching vs. black) of the simulated scotoma. Critically, the spatial-frequency performance cost on response time was abolished selectively under the black-scotoma-with-phosphene condition (χ[2](3) = 8.72, p = 0.033), whereas it remained significant under all invisible scotoma conditions, indicating that a perceptually distinct scotoma background enhances the detectability of phosphene signals. These differences were reflected corroborated by systematic divergences in gaze trajectory length and terminal fixation location across conditions. Significance. Our findings suggest that variability in scotoma perception constitutes an important, yet underexplored, factor contributing to inter-individual differences in the effectiveness of retinal prosthetic stimulation. Accounting for perceptual properties of scotomas may provide a framework for optimizing stimulation strategies and improving functional outcomes of future retinal prostheses.},
}

@article {pmid42697260,
year = {2026},
author = {Pourbagherkhah, P and Jaldian, HB},
title = {Biomarkers for Detecting and Predicting Macular Neovascularization in Age-Related Macular Degeneration Using Optical Coherence Tomography Angiography: A Systematic Review.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105637},
doi = {10.1016/j.pdpdt.2026.105637},
pmid = {42697260},
issn = {1873-1597},
abstract = {PURPOSE: This systematic review evaluates the role of optical coherence tomography angiography (OCTA)-based biomarkers in detecting and predicting macular neovascularization (MNV) in age-related macular degeneration (ARMD).

METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus and Google Scholar up to 20 May 2026, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Inclusion criteria encompassed original cohort and cross-sectional studies reporting OCTA-derived quantitative and qualitative biomarkers associated with MNV.

RESULTS: A total of 203 articles were initially identified, with 11 studies meeting the eligibility criteria, comprising 642 eyes. Key OCTA biomarkers included vascular density, MNV area, total vessel length, and choroidal vascularity index, which demonstrated strong associations with disease activity and progression.

CONCLUSION: OCTA-derived biomarkers offer a non-invasive and effective means for detecting and monitoring MNV in ARMD. Despite current challenges in standardization and interpretation, integrating these biomarkers into clinical practice could improve early diagnosis and personalized treatment strategies.},
}

@article {pmid42697271,
year = {2026},
author = {Kardo, H and Garweg, RA and Imbach, L and Garweg, JG},
title = {Longitudinal Changes in Inner Retinal Layers in Treatment-Naïve Neovascular AMD During Intravitreal Anti-VEGF Therapy.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.08.031},
pmid = {42697271},
issn = {2468-6530},
abstract = {PURPOSE: To investigate longitudinal changes in retinal nerve fiber layer (RNFL) and ganglion cell- inner plexiform layer (GC-IPL) thickness in treatment-naïve neovascular age-related macular degeneration (nAMD) under intravitreal anti-VEGF therapy (IVT), compared with untreated fellow eyes with dry AMD (dAMD).

DESIGN: Retrospective single-center cohort study.

SUBJECTS: Consecutive patients with treatment-naïve nAMD receiving anti-VEGF therapy under a treat-and-extend regimen and a minimum follow-up of 24 months were included. Untreated fellow eyes with dAMD served as controls.

METHODS: RNFL and GC-IPL thickness were assessed longitudinally using spectral-domain optical coherence tomography and RetinAI analysis. Best-corrected visual acuity (BCVA) and structural retinal changes were evaluated over time. Linear mixed-effects models were used to assess factors associated with retinal layer changes.

MAIN OUTCOME MEASURES: Longitudinal changes in RNFL thickness, GC-IPL thickness, and BCVA.

RESULTS: In nAMD eyes, median RNFL thickness in the 3 mm ring zone decreased from 32.3 μm (30.1-35.4) at baseline to 30.9 μm (29.0-33.4; adjusted P < .001) after the loading phase and remained stable thereafter (all adjusted P > .05), with a similar pattern observed in fellow dAMD eyes. In contrast, GC-IPL thickness progressively declined in both groups. In nAMD eyes, median GC-IPL thickness decreased from 89.1 μm (81.9-94.9) at baseline to 85.1 μm (77.7-90.2) after loading (adjusted P < .001), followed by continued thinning throughout follow-up. BCVA in nAMD eyes improved after loading with a median gain of 4.8 ETDRS letters (0-10.2; adjusted P < .001), remained stable for up to 3 years, and gradually declined thereafter. Mixed-effects modeling showed RNFL thickness was associated with injection number, whereas GC-IPL loss was associated with age and follow-up duration, independent of injection number or sex.

CONCLUSIONS: The regression in RNFL and GC-IPL thickness during the loading phase in eyes with nAMD may reflect the resolution of pre-treatment swelling. RNFL thickness remained stable thereafter, while GC-IPL thickness and BCVA declined after loading similarly to fellow eyes with dAMD. According to the mixed-effects model, GC-IPL thinning appears linked to progression of the underlying degenerative process, whereas RNFL thickness appears comparatively preserved.},
}

@article {pmid42697425,
year = {2026},
author = {Sun, X and Zhang, G and Feng, X and Hong, Z and Qu, Y and Li, M and Xia, Z and Xu, J and Bachwenkizi, J and Lam, H and Wang, Y and Honda, Y and Hashizume, M and Chen, R and Wu, Z and Ji, JS and Liang, D and Guo, Y and Kan, H and Jia, H and Wong, TY},
title = {Exposome for Ocular Diseases: From Exposure Evidence to Causality and Actionable Prevention.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101524},
doi = {10.1016/j.preteyeres.2026.101524},
pmid = {42697425},
issn = {1873-1635},
abstract = {The exposome, defined as the totality of external exposures individuals experience throughout the lifespan and the internal biological responses they trigger, is increasingly recognized as a major, modifiable determinant of health. The eye is uniquely vulnerable to exposome risk factors because it comprises an external interface directly exposed to the environment, a transparent lens highly sensitive to cumulative oxidative injury, and metabolically active retina prone to inflammation and vascular dysregulation. Research linking ocular diseases to air pollution, climate and weather factors, heavy metals, persistent organic pollutants, and emerging threats such as micro-/nanoplastics has expanded rapidly, yet the evidence remains fragmented and lacks systematic integration. In this review, we propose an anatomy-informed ocular exposome atlas along the visual axis to comprehensively evaluate evidence from clinical studies, pathological mechanisms, and intervention strategies across major disease groups-including ocular surface diseases, cataract, refractive errors, glaucoma, and retinal diseases. We further integrate cross-disease mechanistic pathways (oxidative stress, cellular responses, inflammation, immune reactions) and discuss causality. Finally, we identify priority research directions and provide actionable recommendations for prevention and policy.},
}

@article {pmid42696011,
year = {2026},
author = {Kozlov, M and Sadeghi, E and Chhablani, J},
title = {Adoption patterns of anti-vascular endothelial growth factor therapies in retinal disease.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42696011},
issn = {1435-702X},
abstract = {PURPOSE: To characterize real-world adoption patterns of anti-vascular endothelial growth factor (anti-VEGF) therapies across retinal vascular diseases.

METHODS: This retrospective cohort study identified patients diagnosed with exudative age-related macular degeneration (AMD), diabetic macular edema (DME), or retinal vein occlusion (RVO) within TriNetX. Monthly utilization of ranibizumab, bevacizumab, aflibercept, brolucizumab, and faricimab was measured across each indication. To provide absolute treatment context, we also determined the annual number of unique patients within each disease cohort with at least one documented exposure to any evaluated anti-VEGF agent.

RESULTS: The cohorts included 138,384 AMD patients, 322,865 DME patients, and 105,605 RVO patients. Aflibercept demonstrated sustained long-term utilization across all three indications, whereas faricimab showed rapid early uptake after its introduction. Ranibizumab utilization declined over time, while brolucizumab demonstrated limited and transient uptake. The annual number of patients receiving anti-VEGF treatment increased substantially over the observation period and reached 16,319 in AMD, 12,105 in DME, and 6,873 in RVO in 2023.

CONCLUSION: Real-world adoption of anti-VEGF therapies differs markedly across retinal diseases and agents. Aflibercept demonstrated sustained long-term use, while faricimab showed rapid early uptake. Changes in agent-specific utilization occurred alongside substantial growth in the absolute number of treated patients over the study period, underscoring the importance of interpreting drug-specific trajectories in the context of overall treatment activity.},
}

@article {pmid42690636,
year = {2026},
author = {Chen, S and Li, Y and Xuan, M and Xiong, R and Tan, S and Wang, W},
title = {Longitudinal Trajectories of 3-Dimensional Eye Shape and Pathological Sequelae in High Myopia.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42690636},
issn = {2168-6173},
abstract = {IMPORTANCE: The highly myopic eye remodels in 3 dimensions, but the longitudinal trajectories of globe shape and their associations with sight-threatening outcomes remain poorly defined.

OBJECTIVE: To characterize 15-year 3-dimensional (3D) remodeling trajectories of highly myopic globes and examine their associations with baseline features and ocular outcomes.

This 15-year 3D magnetic resonance imaging (MRI) cohort substudy was nested within the Zhongshan High Myopia Cohort. Thirty participants (60 eyes) with bilateral high myopia (spherical equivalent refraction, -6.00 D or worse) randomly drawn from 95 participants imaged in September 2011 were rescanned in September 2025.

EXPOSURES: Orbital 3D MRI reconstructions were classified into 6 globe-shape categories. Paired classifications, global enlargement, and staphyloma status defined 5 remodeling patterns: quiescence, proportional expansion, focal emergence, focal progression, and shape transition.

MAIN OUTCOMES AND MEASURES: Distribution of remodeling patterns and their associations with myopic macular degeneration (MMD), myopic traction maculopathy (MTM), posterior staphyloma (PS), visual acuity, and visual field indices.

RESULTS: Among the 30 included participants, the mean (SD) age was 37.30 (15.89) years, and 16 (53.3%) participants were women. The 60 eyes were classified as quiescent (21 [35.0%]), proportional expansion (12 [20.0%]), focal emergence (14 [23.3%]), focal progression (6 [10.0%]), or shape transition (7 [11.7%]). No deformed eye reverted to spheroidal. Pattern distribution was associated with baseline age and contour: 10 of 12 eyes (83.3%) of individuals younger than 20 years underwent proportional expansion, whereas 13 of 24 eyes (54.2%) of individuals aged 40 years and older followed focal progression or shape transition. Eyes with focal emergence had the largest best-corrected visual acuity decline (0.26 logMAR) and mean deviation worsening (-3.50 dB), and eyes with shape transition had the largest pattern standard deviation increasing (1.95 dB). At similar axial elongation, eyes developing focal deformation had higher frequencies of MMD progression (91.7%; 95% CI, 74.2-97.7 vs 58.8%; 95% CI, 36.0-78.4; P = .02), incident or progressive PS (91.7%; 95% CI, 74.2-97.7 vs 17.6%; 95% CI, 6.2-41.0; P < .001), and MTM (58.3%; 95% CI, 38.8-75.5 vs 11.8%; 95% CI, 3.3-34.3; P = .003).

CONCLUSIONS AND RELEVANCE: Highly myopic globes followed age- and geometry-associated trajectories linked to outcomes beyond axial elongation. These 2-time-point findings potentially support 3D shape analysis as a candidate framework for individualized surveillance, pending prospective validation.},
}

@article {pmid42693542,
year = {2026},
author = {Jung, W and Lee, JJ and Cho, Y and Min, KA and Yun, HY and Lee, S and Yang, J and Chae, JW},
title = {Determination of Human Effective Dose via Translational Ocular Modeling: Clinical Translation of a Novel Topical Agent Using PBPK.},
journal = {Clinical and translational science},
volume = {19},
number = {9},
pages = {e70717},
pmid = {42693542},
issn = {1752-8062},
support = {RS-2022-00155857//Korea Government/ ; RS-2023-00278597//Korea Government/ ; RS-2022-NR069643//Korea Government/ ; RS-2022-NR070856//Korea Government/ ; RS-2021-KE001333//Core Technology Development Project for Environmental Diseases Prevention and Management/ ; //Korea Ministry of Environment (MOE)/ ; //Korea Machine Learning Ledger Orchestration for Drug Discovery Project (K-MELLODDY)/ ; RS-2024-00460694//Ministry of Health & Welfare and Ministry of Science and ICT, Republic of Korea/ ; 2710008763//Korea Institute of Toxicology (KIT) Research Program/ ; KK-2401-01//Korea Institute of Toxicology (KIT) Research Program/ ; //Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI)/ ; RS-2024-00336984//Ministry of Health & Welfare, Republic of Korea/ ; RS-2025-02306055//Ministry of Health & Welfare, Republic of Korea/ ; RS-2024-00434342//Korea Institute for Advancement of Technology (KIAT)/ ; //National Research Foundation of Korea (NRF)/ ; RS-2025-25397599//Ministry of Education/ ; //EyeBioKorea/ ; },
mesh = {Humans ; Animals ; Rabbits ; Mice ; *Models, Biological ; *Macular Degeneration/drug therapy ; Translational Research, Biomedical ; Dose-Response Relationship, Drug ; *Ophthalmic Solutions/administration & dosage/pharmacokinetics ; Computer Simulation ; Tissue Distribution ; Species Specificity ; Male ; },
abstract = {Wet age-related macular degeneration (wAMD) is a leading cause of vision loss, and human dose selection for ocular therapeutics remains a key translational challenge. We developed a physiologically based pharmacokinetic (PBPK) model for EB-203 to guide dose selection by translating preclinical ocular tissue exposure to human. PK data were obtained from mouse and rabbit studies and human plasma PK from a phase I trial. The model incorporated species-specific ocular physiology, drug permeability, and pharmacokinetics, and was implemented using an open-source PBPK modeling software (MoBi, version 12.2, Open Systems Pharmacology). Drug-specific model parameters were estimated using mouse and rabbit plasma and ocular tissue concentration data. Human plasma PK data from a Phase I clinical trial were then used to estimate human-specific systemic clearance, and human ocular tissue concentrations were subsequently predicted by the model. Simulated human retinal drug concentrations (AUC, Cmax, and Cavr) under multiple dosing regimens were evaluated against preclinical efficacy thresholds to determine the optimal dosing strategy. The model adequately described drug disposition across species, with most predicted PK parameters falling within a 2-fold error of the observed data. Simulations suggested that a 4% four-times-daily dosing regimen in humans achieves retinal exposure comparable to the efficacious mouse concentrations. No significant systemic accumulation was observed, indicating a favorable safety profile. This PBPK framework provides a practical approach for predicting human ocular drug exposure and can be adapted to other compounds or ocular indications in the absence of direct tissue sampling. These results support further clinical evaluation of EB-203 for the treatment of wAMD.},
}

Humans
Animals
Rabbits
Mice
*Models, Biological
*Macular Degeneration/drug therapy
Translational Research, Biomedical
Dose-Response Relationship, Drug
*Ophthalmic Solutions/administration & dosage/pharmacokinetics
Computer Simulation
Tissue Distribution
Species Specificity
Male

@article {pmid42694158,
year = {2026},
author = {Jin, E and Zhu, X and Li, S and Zhao, M and Miao, H and Qian, T},
title = {Short-term morphological and functional outcomes of intravitreal faricimab for chorioretinal disorders: a real-world study in a Chinese population.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1909782},
pmid = {42694158},
issn = {2296-858X},
abstract = {OBJECTIVE: To evaluate the real-world efficacy and safety of the bispecific antibody faricimab in Chinese patients with neocascular age-related macular degeneration (nAMD), diabetic macular edema (DME), and macular edema secondary to retinal vascular occlusion (RVO-ME).

METHODS: This retrospective, single-center study included 63 patients (74 eyes: 47 nAMD, 19 DME, 8 RVO-ME); no subjects dropped out. Of the 74 eyes, 37.8% were treatment-naïve and 62.2% were treatment-experienced. All eyes received intravitreal faricimab 6 mg in a three-dose loading regimen followed by pro re nata (PRN) retreatment. Best-corrected visual acuity (BCVA, ETDRS letters) and central macular thickness (CMT) were assessed at baseline, 1 month, 3 months, and final follow-up (mean follow-up, 23.9 ± 12.3 weeks). Subgroup analyses by prior treatment status were performed.

RESULTS: Faricimab was associated with anatomical and functional improvements. In nAMD, treatment-naïve patients (n = 17) showed significant BCVA improvement (62.52 ± 5.80 to 71.05 ± 15.68 letters, P = 0.037) and CMT reduction (477.86 ± 189.45 to 324.19 ± 137.62 μm, P = 0.001) at final follow-up. Previously-treated nAMD patients (n = 30) showed only a transient CMT reduction at 3 months (P = 0.022) without sustained visual improvement. After the first injection, intraretinal fluid resolved in 90% of nAMD eyes that had IRF at baseline. After three loading doses, complete resolution of subretinal fluid and pigment epithelial detachment (PED) occurred in 66.7% and 31.3% of eyes, respectively. In DME, treatment-naïve patients (n = 9) achieved early BCVA improvement at 1 month (P = 0.0273) and sustained benefit at final follow-up (P = 0.0180), whereas previously-treated patients (n = 10) showed delayed improvement at 3 months in both BCVA and CMT (P = 0.0117 and 0.0195). In RVO-ME, BCVA improved significantly at 3 months and final follow-up (P = 0.018 and 0.028), whereas CMT showed a nonsignificant decrease. No significant ocular or systemic adverse events were observed.

CONCLUSION: In this short-term real-world study comprising three exploratory disease-specific cohorts of Chinese patients, faricimab was associated with favorable anatomical and functional outcomes and was well tolerated, with the most pronounced benefit in treatment-naïve nAMD eyes. Responses in DME and RVO-ME were more variable and appeared to be influenced by prior treatment history; these subgroup analyses were exploratory, and larger prospective studies are warranted.},
}

@article {pmid42684442,
year = {2026},
author = {Bandello, F and Borrelli, E and De Falco, S and Invernizzi, A and Lanzetta, P and Lupidi, M and Midena, E and Ricci, F and , },
title = {Aflibercept 8 mg for diabetic macular edema and neovascular age-related macular degeneration: an italian expert consensus paper.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42684442},
issn = {1435-702X},
abstract = {PURPOSE: To provide consensus recommendations on the clinical use of aflibercept 8 mg in managing neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) in the real-world setting.

METHODS: A modified Delphi study was undertaken, involving ophthalmologists from specialized centers in Italy, to gauge consensus on statements related to the use of aflibercept 8 mg in nAMD and DME. Two initial rounds of online surveys were conducted, followed by 2 workshops to assess the clinical feasibility of selected statements and identify the behavioral drivers and barriers to their adoption in practice. Consensus was defined as ≥ 75% agreement ('strongly agree' or 'somewhat agree').

RESULTS: Consensus was reached for 30 initial statements, following refinement and discussion. Of these, 12 statements were analyzed and discussed at the behavioral workshop. Statements covered clinical differentiation of aflibercept 2 mg and 8 mg, treatment initiation in aflibercept-naïve patients, switching to aflibercept 8 mg, optimal aflibercept 8 mg maintenance, and safety considerations. There was expert group consensus that aflibercept 8 mg represents a viable treatment option with an extended injection interval for patients with nAMD or DME, with the possibility of improving treatment adherence, and therefore outcomes. Experts also discussed practical considerations in Italy and offered evidence-based guidance.

CONCLUSION: Experts agreed that aflibercept 8 mg is a treatment option for both nAMD and DME with the potential to improve treatment adherence. Although real-world data are limited, experts offered guidance on the management of nAMD and DME in the context of aflibercept 8 mg.},
}

@article {pmid42685076,
year = {2026},
author = {Cheng, FF and Mou, H and Liu, Z and Zhang, CJ and Zhuang, YY and Wu, Z and Wen, XR and Xue, A and Zhang, X and Yang, J and Jin, ZB},
title = {Genetic evidence and cross-species functional characterization implicate CNN2 in age-related macular degeneration susceptibility.},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {123},
number = {36},
pages = {e2533682123},
doi = {10.1073/pnas.2533682123},
pmid = {42685076},
issn = {1091-6490},
support = {82125007//MOST | National Natural Science Foundation of China (NSFC)/ ; 92368206//MOST | National Natural Science Foundation of China (NSFC)/ ; CX23YZ14//Chinese Institutes for Medical Research/ ; BRWEP2024W172050100//Beijing Research Ward Excellence Program/ ; PWD&RPP-MRI//Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes/ ; JYY2023-6//Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes/ ; U23A20165//MOST | National Natural Science Foundation of China (NSFC)/ ; 2024SSYS0032//"Pioneer" and "Leading Goose" R&D Program of Zhejiang/ ; 2022SDXHDX0001//"Pioneer" and "Leading Goose" R&D Program of Zhejiang/ ; },
mesh = {Animals ; *Genetic Predisposition to Disease ; *Macular Degeneration/genetics/pathology/metabolism ; Zebrafish ; Quantitative Trait Loci ; Genome-Wide Association Study ; Mice ; Humans ; Cytoskeletal Proteins/genetics/metabolism ; Disease Models, Animal ; },
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment in the aging population globally. Although genome-wide association studies (GWAS) have identified many AMD susceptibility loci, the genes and mechanisms underlying many of these associations remain unresolved. Here, we integrated expression quantitative trait locus (eQTL) data with AMD GWAS to prioritize nine putative genes. Through in vivo screening in zebrafish, we demonstrated that the downregulation of cnn2 and sarm1 expression led to ocular structural abnormalities and visual functional impairment. Subsequent mouse model studies confirmed that Cnn2 deficiency affected photoreceptor structure and function, impaired contrast sensitivity, and caused abnormalities in cone cell immunostaining. Given that CNN2 is predominantly expressed in endothelial cells, we propose that endothelial dysfunction may cascade to impair photoreceptor function. Collectively, through in silico prioritization and cross-species functional characterization, we identify CNN2 as a candidate susceptibility gene in AMD pathogenesis, providing vital underlying mechanistic insights.},
}

Animals
*Genetic Predisposition to Disease
*Macular Degeneration/genetics/pathology/metabolism
Zebrafish
Quantitative Trait Loci
Genome-Wide Association Study
Mice
Humans
Cytoskeletal Proteins/genetics/metabolism
Disease Models, Animal

@article {pmid42686244,
year = {2026},
author = {Manikya, S and Vadhithala, V and Kumar, R and Nainwal, P},
title = {Re: Holz et al.: Adherence to intravitreal aflibercept in neovascular age-related macular degeneration: 24-month results from the ANDROMEDA Study (Ophthalmol. Retina. 2026;10:241-249).},
journal = {Ophthalmology. Retina},
volume = {10},
number = {9},
pages = {e81-e82},
doi = {10.1016/j.oret.2026.06.013},
pmid = {42686244},
issn = {2468-6530},
}

@article {pmid42687065,
year = {2026},
author = {Attia, SA and Tse, AM and Ramirez, AD and Izadiar, M and Liu, Y and Guo, H and Albanese, A and Cohn, W and MacKay, AW and Seidler, PM and Kannan, R and Sreekumar, PG and MacKay, JA},
title = {αB-crystallin elastin-like polypeptides for sustained ocular drug delivery.},
journal = {Drug delivery and translational research},
volume = {},
number = {},
pages = {},
pmid = {42687065},
issn = {2190-3948},
abstract = {The unfolded protein response (UPR) has been mechanistically implicated in multiple ocular disorders, including age-related macular degeneration (AMD). Therapeutic intervention using an αB-crystallin-derived 'mini-cry' chaperone peptide has potential to restore proteostasis; however, its low molecular weight results in rapid ocular clearance. To prolong mini-cry's ocular effects, our team linked it with elastin-like polypeptides (ELPs). ELPs are thermoresponsive polymers that phase-separate into microscale coacervates. Provided ELPs do not interfere with biological activity, cry-ELPs could prolong intraocular retention and improve therapeutic effect. This study compares two cry-ELPs (cry-SI and cry-V96) designed to phase-separate following intravitreal administration. First, chaperone activity was assessed using tau protein aggregation assays, demonstrating that cry-V96 exhibited superior inhibition of tau seeding and fibril disaggregation. Second, modulation of the UPR was assessed in human retinal pigment epithelium cells using tunicamycin-induced stress. Both constructs suppressed PERK/ATF-4/CHOP signaling, with cry-V96 showing the most robust attenuation of ER stress. Third, cellular uptake and subcellular localization were analyzed by biochemical fractionation and Western blotting, revealing enhanced cellular uptake and association and stress-dependent nuclear localization of cry-ELPs, compared to controls. Fourth, the lead construct, cry-V96, was evaluated in vivo in rabbit eyes, where it formed a sustained intravitreal depot, exhibited prolonged retention, and showed no evidence of ocular toxicity by fluorescence imaging and optical coherence tomography (OCT). Finally, proteomic profiling using liquid chromatography-tandem mass spectrometry (LC-MS/MS) identified 59 proteins selectively enriched by cry-V96, implicating pathways involved in proteostasis, intracellular trafficking, and stress adaptation. Collectively, these findings establish cry-ELPs as multifunctional molecules that combine potent chaperone activity with sustained ocular delivery, providing a promising strategy for targeting UPR dysregulation in AMD and related degenerative diseases.},
}

@article {pmid42687870,
year = {2026},
author = {Mandal, D and Roy, A and Chen, X and Zhong, JF and Kim, ES},
title = {Microfluidic platform for nanoliter qPCR of several retinal pigment epithelial (RPE) cells.},
journal = {Journal of micromechanics and microengineering : structures, devices, and systems},
volume = {36},
number = {9},
pages = {095001},
pmid = {42687870},
issn = {0960-1317},
abstract = {The clinical implant of stem cell-derived retinal pigment epithelium (RPE) monolayer for age-related macular degeneration requires rigorous validation of the monolayer's cellular maturity. Conventional bulk molecular assays lack the sensitivity to resolve cellular heterogeneity and are prone to damaging the RPE monolayer. This study developed and validated an automated nanoliter-scale microfluidic platform for single-cell transcriptomic quality control of engineered RPE monolayers. A compact polydimethylsiloxane -based microfluidic platform was developed to generate monodisperse 10 nL RPE cell cDNA droplets and 90 nL quantitative PCR (qPCR) reagent droplets using dual-focused-flow geometries. Deterministic droplet fusion was achieved via direct current electrocoalescence, enabling ∼100% merging efficiency. An auxiliary co-flow spacing mechanism was implemented to prevent secondary coalescence during downstream transport. Automated droplet collection into oil-filled 96-well plates was achieved through a custom two-dimensional gantry system, and droplet volume consistency was verified using a Python-based computer vision algorithm. Biological validation was conducted using H14 human embryonic stem cell-derived RPE cells targeting β-actin and lineage-specific markers MITF1, MITF2, PEDF, and PMEL17. The platform demonstrated stable generation and deterministic merging of nanoliter droplets, yielding uniform 100 nL reaction volumes suitable for qPCR analysis. Automated volumetric verification confirmed high droplet uniformity and reliability. Gene expression analysis revealed robust detection of housekeeping and lineage-specific genes at nanoliter scales. These findings demonstrated the feasibility of performing nanoliter-scale qPCR using the proposed microfluidic workflow. The workflow enabled reliable detection of extremely low quantities of nucleic acid using a widely available commercial qPCR platform, providing a practical and accessible approach for routine laboratory and translational research applications. The system-maintained assay sensitivity while significantly reducing reagent consumption and sample input. This automated microfluidic platform enabled reproducible, sample-efficient, single-cell transcriptomic validation of stem cell-derived RPE monolayers. By integrating droplet generation, deterministic merging, automated collection, and computational verification, the system addressed key limitations of bulk molecular quality control of RPE monolayers. This work established a scalable and cost-effective nanoliter qPCR framework for high-resolution molecular quality assurance of regenerative cell therapies.},
}

@article {pmid42687910,
year = {2026},
author = {Swaroop, A and Marchal, C and Gaur, M and Kumari, A and Mohan, S and Brooks, M and Jaeger, C and Advani, J and Campello, L and English, M and Singh, N and Diaz, X},
title = {Enhanced chromatin compaction is associated with de novo expression of a nuclear microprotein, global loss of H3 acetylation and local transcriptional changes in retinal rod photoreceptors.},
journal = {Research square},
volume = {},
number = {},
pages = {},
doi = {10.21203/rs.3.rs-10017071/v1},
pmid = {42687910},
issn = {2693-5015},
abstract = {We have limited understanding of how aging alters gene expression and remodels cellular architecture in post-mitotic neurons. The inverted nuclear organization of mouse rod photoreceptors provides a unique model to gain mechanistic insights into age-associated decline in neuronal function. We have generated and integrated multi-omic datasets including 3D-genome topology, histone modifications, chromatin accessibility, DNA methylation and transcriptome of rod photoreceptors from young- and aged-mice. We show that aging drives global chromatin compaction, with regional alterations enriched at active chromatin. Epigenomic and transcriptional changes broadly correlate with chromatin dynamics as validated by high resolution microscopy. We uncover a megabase-sized genomic region with multi-level alterations, including de novo transcription of Gm7239, which encodes a functional microprotein carrying histone acetyltransferase-inhibitor domain. Overexpression of Gm7239 is associated with global loss of histone H3 acetylation, highlighting a potential new axis of genomic regulation in aging. Finally, we identify multiple significant local transcriptional alterations in non-annotated regions and genes associated with age-related macular degeneration. Our studies link age-related chromatin landscape changes with gene expression that may influence rod function and vulnerability to diseases.},
}

@article {pmid42681078,
year = {2026},
author = {Cheong, KX and Jiang, Y and Xu, X and Htoon, HM and Foo, LL and Lamoureux, EL and Hoang, QV and Lan, W and Saw, SM},
title = {Two-Year Fundus Progression in Highly Myopic Eyes in the Aier-SERI High Myopia Adult Cohort Study.},
journal = {Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians (Optometrists)},
volume = {},
number = {},
pages = {},
pmid = {42681078},
issn = {1475-1313},
support = {2024RC5002, 2023RC1079//Science and Technology Innovation Program of Hunan Province, China/ ; JRDUKY004900//Duke-NUS Distinguished Professorship grant/ ; },
abstract = {PURPOSE: To evaluate 2 year fundus progression and associated factors in adults in the Aier-SERI High Myopia cohort in Changsha, China.

METHODS: A total of 367 adult high myopes (spherical equivalent [SE] ≤ -5.0D) underwent baseline and 2 year assessments, including colour fundus photography graded by the Meta-analysis for Pathologic Myopia (META-PM) classification. Progression was defined as advancement to a higher category, enlargement of atrophy or development/worsening of plus lesions. Associations were analysed using multivariable generalised estimating equation (GEE) logistic regression adjusting for age, sex, SE or axial length (AL) and baseline META-PM category.

RESULTS: In this cohort (mean age: 45.2 ± 7.3 years), fundus progression occurred in 31/734 eyes (4.2%, 27 participants). Of 37 lesion changes in 31 eyes, the most frequent changes were enlargement of patchy atrophy (51.4%), followed by diffuse atrophy (16.2%) and lacquer crack extension (16.2%). Fuchs' spot expansion and category progression were less common (8.1% each). In GEE models, progression was associated with more myopic SE (per -1D, odds ratio [OR]: 1.21; 95% confidence interval [CI]: 1.14-1.29, p < 0.001), longer AL (per 1-mm, OR: 1.96; 95% CI: 1.64-2.34, p < 0.001) and older age (per year, OR: 1.06; 95% CI: 1.02-1.11, p < 0.01). Eyes with baseline Category 3 lesions had markedly higher odds of progression (OR: 85.55; 95% CI: 25.07-291.93, p < 0.001).

CONCLUSIONS: Over 2 years, fundus progression in adult highly myopes occurred mainly in those with advanced atrophy at baseline and was associated with greater myopia, longer AL and older age. Eyes of Categories 0-1 remained stable, suggesting a threshold for accelerated degeneration.},
}

@article {pmid42681693,
year = {2026},
author = {Ruiz-Medrano, J and Zamorano, M and de Alboran, CM and Ruiz-Moreno, JM},
title = {Two-year real-world effectiveness of faricimab after treatment switch in neovascular age-related macular degeneration.},
journal = {International journal of retina and vitreous},
volume = {12},
number = {1},
pages = {},
pmid = {42681693},
issn = {2056-9920},
abstract = {PURPOSE: To evaluate the 2-year real-world outcomes of switching to intravitreal faricimab in patients with neovascular age-related macular degeneration (nAMD) previously treated with anti-VEGF agents and unable to extend treatment intervals (TI) beyond 12 weeks.

METHODS: Prospective cohort study including patients with nAMD managed under a treat-and-extend regimen who required frequent anti-VEGF injections (< 12-week intervals) to maintain retinal dryness. Patients were switched to faricimab without a loading phase and followed for a minimum of 2 years. TI were extended in 4-week increments based on anatomical response. The primary outcome was change in TIl; secondary outcomes included change in best-corrected visual acuity (BCVA) and identification of predictors of response. "Optimal responders" were defined as eyes achieving ≥ 8-week interval extension.

RESULTS: A total of 110 eyes from 97 patients were included (mean age 78.7 ± 9.8 years). Prior to switching, the mean TI was 6.18 ± 2.05 weeks, which increased significantly to 13.61 ± 5.62 weeks at the last follow-up visit (p < 0.001). BCVA remained stable over 2 years (0.42 ± 0.24 vs. 0.43 ± 0.25; p = 0.0117). At final follow-up, 68.2% of eyes achieved intervals ≥ 12 weeks, 20.0% ≥16 weeks, and 24.6% reached ≥ 20-week intervals. Overall, 89.1% of eyes experienced interval extension. Optimal responders accounted for 47.3% of eyes and were significantly younger and had received fewer prior injections (p < 0.05).

CONCLUSIONS: Switching to faricimab in previous treated nAMD patients enabled meaningful extension of TI over 2 years while maintaining stable visual acuity. These findings support faricimab as an effective strategy to reduce treatment burden in patients who are difficult to extend with prior anti-VEGF therapies.},
}

@article {pmid42682018,
year = {2026},
author = {Swan, J and Gagneux, P},
title = {Glycosylation of the retina.},
journal = {Biochemical Society transactions},
volume = {54},
number = {9},
pages = {1183-1192},
pmid = {42682018},
issn = {1470-8752},
support = {M2023003F//BrightFocus Foundation (BFF)/ ; },
mesh = {Glycosylation ; Humans ; *Retina/metabolism ; Animals ; Polysaccharides/metabolism ; Proteoglycans/metabolism ; Glycosphingolipids/metabolism ; Retinal Diseases/metabolism ; },
abstract = {Unlike the cornea and tear fluid, glycosylation within the retina remains remarkably underexplored. This review highlights the diverse roles of glycans in retinal development and vision, with a focus on major glycan classes, including glycosphingolipids (GSLs; glycans attached to lipids), N- and O-linked glycans on proteins, glycosaminoglycans (GAGs) on proteoglycans, O-mannosylated proteoglycans, and intracellular O-GlcNAcylation. Together, these components provide a comprehensive framework for understanding glycan-mediated processes in retinal biology. Current knowledge of the retinal glycosylation nanolandscape, primarily derived from lectin binding and anti-glycan antibody studies, is summarised. The review also examines the roles of altered glycosylation in immune regulation and retinal diseases such as retinitis pigmentosa, age-related macular degeneration and diabetic retinopathy. Finally, key gaps in knowledge and priority areas for future research are discussed. The retina remains understudied with regard to the complex patterns of glycosylation. Alterations of these patterns could represent consequences or be driving pathology, given the well-established roles of glycan patterns in development and homeostasis in other tissues.},
}

Glycosylation
Humans
*Retina/metabolism
Animals
Polysaccharides/metabolism
Proteoglycans/metabolism
Glycosphingolipids/metabolism
Retinal Diseases/metabolism

@article {pmid42683940,
year = {2026},
author = {Guo, CW and Zhao, AH and Kaelber, D and Singh, RP and Talcott, KE},
title = {Effect of Hormone Replacement Therapy on Risk of Age-related Macular Degeneration Among an Aggregate Health Record Cohort.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {},
number = {},
pages = {1-9},
doi = {10.3928/23258160-20260813-03},
pmid = {42683940},
issn = {2325-8179},
abstract = {BACKGROUND AND OBJECTIVE: Estrogen in hormone replacement therapy (HRT) exerts anti-inflammatory effects believed to oppose age-related macular degeneration (AMD) pathogenesis, but whether HRT can be protective against AMD is contested. The aim of the study was to evaluate the association between HRT use and the risk of development and progression of AMD in postmenopausal women.

PATIENTS AND METHODS: This was a retrospective cohort study utilizing ICD-10 codes for HRT usage and rates of AMD development and progression.

RESULTS: There was a decreased risk of developing AMD in patients more than 60 years of age at 5 years (RR 0.72, 95% CI: 0.63-0.82) and 8 years (0.68, 0.60-0.76) after HRT initiation. Patients more than 75 years of age also demonstrated a reduced risk of developing AMD after 5 years (0.70, 0.60-0.82) and 8 years (0.64, 0.56-0.74) of HRT use. Patients more than 75 years of age had a reduced risk of progression to exudative AMD at 8 years (0.66, 0.49-0.89) after HRT initiation.

CONCLUSION: HRT may be associated with a decreased risk of developing AMD, with continued effects at more chronic timepoints after HRT initiation.},
}

@article {pmid42676384,
year = {2026},
author = {Wang, MH and Lee, SMY and Wang, Y and Alves, JC and Xie, R and He, Y and Hou, G and Fang, X and Yu, Y and Cai, X and Zheng, S and Liu, J and Cheang, C and Kuok, KI and Qin, S},
title = {Artificial intelligence for precision therapeutics in age-related macular degeneration: current advances, challenges, and future directions.},
journal = {Frontiers in artificial intelligence},
volume = {9},
number = {},
pages = {1822604},
pmid = {42676384},
issn = {2624-8212},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss worldwide and is characterized by substantial clinical, imaging, and molecular heterogeneity that complicates disease prediction and therapeutic management. Recent advances in artificial intelligence (AI) and precision therapeutics have created new opportunities for more individualized and data-driven AMD care. AI models trained on multimodal datasets-including fundus photography, optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), genetic susceptibility loci (e.g., CFH, ARMS2/HTRA1, C3, CFI, and APOE), and longitudinal clinical information-have demonstrated promising capability in early disease detection, progression forecasting, biomarker identification, and prediction of treatment response. These developments align closely with emerging precision therapeutic strategies, including optimized anti-vascular endothelial growth factor (anti-VEGF) regimens, complement-targeted therapies, gene-based interventions, and stem cell-associated regenerative approaches. This review provides a translational overview of AI-enabled precision therapeutics in AMD, with emphasis on multimodal biomarker integration, individualized therapeutic stratification, longitudinal disease monitoring, and clinically interpretable AI systems. Importantly, we further propose a Five-Level Clinical Readiness and Translational Utility Framework for AI in AMD Precision Therapeutics, categorizing AI applications according to evidence strength, clinical maturity, validation status, interpretability, and real-world implementation potential. The framework distinguishes near-reference-standard imaging AI systems, advanced clinical decision-support tools, emerging multimodal precision therapeutic AI, supportive workflow-oriented AI systems, and currently limited or unsuitable AI applications. Despite substantial progress, important translational barriers remain, including limited external validation, retrospective study designs, dataset heterogeneity, domain shift, insufficient explainability, regulatory uncertainty, and challenges related to workflow integration and real-world clinical deployment. Future advances in multimodal longitudinal AI, explainable AI, federated learning, digital health platforms, and multi-omics integration may facilitate a transition from reactive disease management toward more proactive, predictive, and personalized ophthalmic care. Collectively, AI-enabled precision therapeutics may help establish a more scalable and clinically integrated framework for individualized AMD management and future precision ophthalmology.},
}

@article {pmid42676770,
year = {2026},
author = {Verma, V and Gupta, S and Singh, P and Karkhur, S and Behera, PR},
title = {Global Patterns of Visual Disability and Low Vision Aid Prescription: A Systematic Review.},
journal = {Cureus},
volume = {18},
number = {7},
pages = {e113756},
pmid = {42676770},
issn = {2168-8184},
abstract = {Visual disability remains a major global public health challenge, particularly among individuals with irreversible ocular diseases where medical or surgical treatment cannot restore functional vision. Low-vision rehabilitation (LVR), including the prescription of low-vision aids (LVAs), plays a critical role in optimizing residual vision and improving quality of life; however, patterns of visual disability and LVA utilization vary widely across populations and healthcare settings. This systematic review was conducted in accordance with PRISMA 2020 guidelines to evaluate patterns of visual disability and the prescription, utilisation, and functional outcomes of low-vision aids across diverse patient populations. Electronic databases, including PubMed, Scopus, EMBASE, and the Cochrane Library, along with Google Scholar and citation tracking, were searched for studies published between 2000 and 2025. Observational studies, randomized or crossover trials, service audits, and rehabilitation reports assessing low-vision rehabilitation or assistive devices were included. Of 975 records identified, 19 studies met the inclusion criteria. Retinal diseases such as age-related macular degeneration, diabetic maculopathy, and inherited retinal dystrophies were the predominant causes of visual disability in adults, whereas congenital and developmental conditions were more common in pediatric populations. Optical LVAs, particularly high-add spectacles and magnifiers, were the most frequently prescribed devices, while electronic and wearable aids demonstrated superior task-specific performance but lower real-world uptake due to cost and usability barriers. Telerehabilitation showed functional outcomes comparable to in-clinic training. Overall, low-vision aids significantly improve functional outcomes across a wide spectrum of visual disabilities, and a multimodal, patient-centered rehabilitation model integrating optical, electronic, and tele-rehabilitation approaches is essential to enhance accessibility, service reach, and effectiveness.},
}

@article {pmid42676855,
year = {2026},
author = {Xiang, Y and Kou, J and Cao, H and Zhang, Y and Cheng, H and Wang, T and Jiang, J and Pan, S and Kang, J and Ding, Y and Wan, W and Zheng, S and Li, M and Huang, X and Hu, K},
title = {Nano-drops of biomimetic macromolecular drugs based on macrophage membranes for targeted treatment of fundus diseases.},
journal = {Materials today. Bio},
volume = {40},
number = {},
pages = {103577},
pmid = {42676855},
issn = {2590-0064},
abstract = {Ocular fundus diseases-including age-related macular degeneration and diabetic retinopathy-are leading causes of irreversible vision loss worldwide. Current macromolecular therapies require frequent intravitreal injections, which increase patient burden and complication risks. To address these limitations, we engineered a macrophage membrane-biomimetic nanovesicle encapsulating ranibizumab (designated M@R) for noninvasive ocular delivery and selective targeting of inflammatory lesions in the posterior segment. In vitro studies demonstrated that M@R retained potent cytokine-scavenging activity against key pro-inflammatory mediators, and the macrophage membrane coating significantly enhanced transcytosis-mediated transport of ranibizumab across ocular epithelial barriers. Ex vivo and in vivo studies confirmed that M@R is capable of noninvasive traversal of ocular barriers, achieving targeted delivery to inflammatory lesions within the fundus. In a laser-induced choroidal neovascularization (CNV) mouse model, topical ocular administration of M@R significantly reduced both the area and thickness of CNV, attributable to its dual anti-inflammatory and anti-VEGF activities. Although multiple dosing was required to achieve therapeutic efficacy comparable to that of a single intravitreal ranibizumab injection, M@R exhibited markedly improved safety profiles, with no observable local ocular toxicity or systemic adverse effects following repeated administration. Collectively, these findings establish macrophage membrane-coated nanovesicles as a promising platform for barrier-penetrating, inflammation-targeted delivery of biologics in the treatment of fundus diseases.},
}

@article {pmid42676917,
year = {2026},
author = {Shen, Y and Xu, X and Yang, Y and Song, Y and Liu, F and Zhao, F},
title = {The COPD-driven "lung-eye axis": mechanisms and clinical evidence of ocular disease.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1893979},
pmid = {42676917},
issn = {2296-858X},
abstract = {COPD is a chronic systemic disease marked by ongoing airflow obstruction, sustained inflammation, and increased oxidative stress, whose pathological impact extends far beyond the lungs. Growing data suggest that COPD impacts the eye via chronic systemic inflammation, intermittent or persistent hypoxia, oxidative stress, and endothelial dysfunction, establishing a cross-system pathological connection termed the "lung-eye axis." Evidence from clinical and experimental studies indicates potential associations between COPD and key ophthalmic conditions, such as dry eye disease, cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration. The underlying mechanisms largely involve the retina and optic nerve, which rely heavily on oxygenation and microvascular homeostasis, highlighting them as prime ocular targets of COPD systemic effects. The application of noninvasive imaging, such as OCT and OCTA, offers quantitative and objective preliminary evidence for the lung-eye axis, indicating that ocular imaging could function as a surrogate marker of systemic disease burden in COPD. Despite being largely cross-sectional and methodologically constrained, the proposed "COPD-driven lung-eye axis" framework offers a cross-organ perspective for understanding the systemic characteristics of COPD. There is an urgent need for large, prospective, multicenter studies combining pulmonary function tests, blood gas measurements, inflammatory biomarker profiling, and multimodal ocular imaging to establish causal links and clinical utility, providing novel strategies for precision stratification and early intervention of COPD-related systemic complications.},
}

@article {pmid42677513,
year = {2026},
author = {Li, Y and Li, B and Zou, D and Zeng, Z and Guo, B and Gong, W and Deng, K and Wang, Z and Zhou, H and Zhou, Y and Xu, X},
title = {Stereospecific Peptide-Polysaccharide Conjugates Enable Noninvasive Therapy of Neovascular Age-Related Macular Degeneration.},
journal = {Journal of the American Chemical Society},
volume = {148},
number = {33},
pages = {35467-35483},
doi = {10.1021/jacs.6c05947},
pmid = {42677513},
issn = {1520-5126},
support = {22077028//National Natural Science Foundation of China/ ; 22277023//National Natural Science Foundation of China/ ; 32000995//National Natural Science Foundation of China/ ; 82271110//National Natural Science Foundation of China/ ; 91956105//National Natural Science Foundation of China/ ; 2025JJ50628//Natural Science Foundation of Hunan Province/ ; 20255098//Scientific Research Project of the Hunan Provincial Health Commission/ ; 2025RC3064//Science and Technology Innovation Program of Hunan Province/ ; 2026JJ20024//Outstanding Young Scientists Program of the Natural Science Foundation of Hunan Province/ ; NA//?Furong Scholar? Distinguished Professor Program in Hunan Province/ ; NA//Flexibly Recruited High-End Talent Program of Yunnan Province/ ; SKY24078//Xiangjiang Public Welfare Foundation of Hunan Province/ ; },
mesh = {Animals ; *Peptides/chemistry/pharmacology/therapeutic use ; *Polysaccharides/chemistry/therapeutic use/pharmacology ; *Macular Degeneration/drug therapy/pathology ; Mice ; Humans ; Stereoisomerism ; *Choroidal Neovascularization/drug therapy ; Cell Proliferation/drug effects ; },
abstract = {Therapeutic interventions for posterior segment ocular diseases, including neovascular age-related macular degeneration (nAMD), remain constrained by poor intraocular bioavailability and the need for repeated intravitreal injections. Here, we introduce a noninvasive therapeutic strategy based on stereospecific peptide-polysaccharide conjugates (PPC) for efficient nAMD treatment. A controllable synthetic strategy was established to generate stereospecific L-PPC and D-PPC, among which D-PPC displayed pronounced chirality-dependent bioactivity, characterized by high-affinity binding to integrin receptors and enhanced inhibition of endothelial/epithelial cell proliferation and migration. Following topical administration, D-PPC efficiently overcame ocular barriers and penetrated choroidal lesions while markedly suppressing pathological angiogenesis in a laser-induced choroidal neovascularization mouse model, comparable to that of intravitreal ranibizumab. We elucidated that stereospecific D-PPC modulates key molecular programs in vivo, including T-cell receptor signaling and cell adhesion molecule pathways. Notably, D-PPC exhibited no detectable ocular or systemic toxicity. This study establishes chirality-engineered peptide-polysaccharide conjugates as a noninvasive and effective therapeutic for posterior ocular diseases, providing a structural and mechanistic blueprint for future translational ophthalmic applications.},
}

Animals
*Peptides/chemistry/pharmacology/therapeutic use
*Polysaccharides/chemistry/therapeutic use/pharmacology
*Macular Degeneration/drug therapy/pathology
Mice
Humans
Stereoisomerism
*Choroidal Neovascularization/drug therapy
Cell Proliferation/drug effects

@article {pmid42678546,
year = {2026},
author = {Piszár, I and Buhl, A and Chronopoulos, A and Schloesser, L and Dicke, C and Eter, N and Zimmermann, JA and , and Finger, RP},
title = {[The oregis IVOM registry-Introduction of a registry for the systematic documentation of representative IVOM treatment data from routine treatment of macular diseases in Germany].},
journal = {Die Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42678546},
issn = {2731-7218},
abstract = {BACKGROUND: Intravitreal operative medication injection (IVOM) treatment in routine clinical practice often fails to achieve the treatment outcomes demonstrated in clinical trials. In Germany, comprehensive and representative real-world data on IVOM treatment (IVT) for macular diseases are still lacking.

OBJECTIVE: Against this background the oregis IVOM registry was established as a subregistry of the national oregis registry. The aim is the standardized collection and analysis of the course of IVOM treatment in the clinical routine in Germany, to evaluate long-term outcomes and identify potential areas for optimizing patient care. In this way participating ophthalmological centers can make an active contribution to the evidence-based development of IVOM treatment.

MATERIAL AND METHODS: The oregis IVOM registry is a prospective, noninterventional observational study. Medical routine care data of adult patients receiving IVOM treatment for neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO) or choroidal neovascularization (CNV) are collected. Data acquisition is performed via web-based remote data entry into an electronic database using REDCap. Registry structure, datasets and data collection parameters are aligned with the international Fight Retinal Blindness! registry.

CONCLUSION: The oregis IVOM registry provides, for the first time, a nationwide structured platform for the systematic collection and evaluation of real-world IVT data in Germany. It closes an important evidence gap in health services research for IVOM treatment in Germany and enables regional and international comparisons as well as analyses of treatment adherence and real-world care.},
}

@article {pmid42680556,
year = {2026},
author = {Gao, Q and Kuo, D and Amason, J and Lee, T and Rathinavelu, JK and Pajic, M and Hadziahmetovic, M},
title = {Modular multi-task deep learning framework for prediction of treatment initiation in neovascular age-related macular degeneration modular AI for NVAMD treatment initiation study-MANTIS.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328327},
pmid = {42680556},
issn = {1468-2079},
abstract = {PURPOSE: The purpose of this study is to develop a fully automated system for determining the optimal time to begin anti-vascular endothelial growth factor (anti-VEGF) treatment, based on retinal changes observed in optical coherence tomography (OCT) images and visual acuity (VA) scores.

METHODS: This retrospective study included two cohorts: patients with intermediate dry age-related macular degeneration (AMD) who did not progress to neovascular AMD (NVAMD) and those who progressed and received anti-VEGF treatment. Subjects had ≥3 consecutive visits. Two tasks were defined: (1) develop a deep learning (DL) model to identify the need for anti-VEGF treatment and (2) estimate outer retina thickness (ORT) from Bruch's membrane to the outer plexiform layer as an imaging biomarker. A convolutional neural network extracted OCT features related to ORT, and two long short-term memory models were trained on separate datasets to address Task I and II treatments.

RESULTS: A total of 122 patients (207 eyes) were included: 49 in dataset 1 (69 eyes; mean (SD) age 84 (8); 25 (51%) female) and 100 in dataset 2 (138 eyes; 82 (7); 54 (54%) female). Task I performance was evaluated by the model's alignment with clinical decisions on anti-VEGF initiation, and demonstrated area under the receiver operating curve of 0.73 (95% CI 0.59 to 0.87), area under the precision-recall curve of 0.51 (95% CI 0.35 to 0.66), an accuracy of 0.87 (95% CI 0.76 to 0.97), a precision of 0.73 (95% CI 0.59 to 0.87), a sensitivity of 0.69 (95% CI 0.54 to 0.83) and a specificity of 0.92 (95% CI 0.84 to 1.00). Task II achieved NMAE 0.12 (95% CI 0.04 to 0.20).

CONCLUSIONS: This DL framework provides a fully automated approach for determining optimal treatment timing, supporting earlier intervention to preserve VA in NVAMD patients.

TRANSITIONAL RELEVANCE: An accurate DL framework that can help with identifying the best time to initiate therapy for NVAMD.},
}

@article {pmid42669559,
year = {2026},
author = {Telegina, DV and Kutlimetova, AO and Izyurov, AE and Kulikov, AV and Kolosova, NG},
title = {Age-Related Alterations in Retinal Monoamine Neuromodulation during AMD-Like Retinopathy Development in Rats.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {8},
pages = {1406-1416},
doi = {10.1134/S0006297926600870},
pmid = {42669559},
issn = {1608-3040},
mesh = {Animals ; *Retina/metabolism/pathology ; Rats ; *Aging/metabolism ; *Macular Degeneration/metabolism/pathology ; Rats, Wistar ; Monoamine Oxidase/metabolism ; *Biogenic Monoamines/metabolism ; Male ; Dopamine/metabolism ; Tyrosine 3-Monooxygenase/metabolism ; },
abstract = {Aging is the major risk factor for age-related macular degeneration (AMD), a leading cause of vision loss in aging populations. Increasing evidence suggests that alterations of neurotransmitter systems contribute to the pathogenesis of AMD. Although biogenic amines in the retina were first detected over 50 years ago, their age-related dynamics and role in AMD development are still poorly understood. Here, we compare age-related changes in the concentrations of norepinephrine, serotonin, dopamine, and their main metabolites in the retinas of senescence-accelerated OXYS rats that develop an AMD-like retinopathy and Wistar rats. We also assessed activities of monoamine oxidases (MAOs) and tyrosine hydroxylase and compared changes in these activities with transcriptome data on genes associated with biogenic amine pathways. The results revealed that in OXYS rats, retinal aging and progression of AMD-like retinopathy are primarily associated with alterations in the dopaminergic system. Specifically, dopamine and its main metabolite DOPAC were present in the retinas at higher levels than serotonin and 5-hydroxyindoleacetic acid. Furthermore, the development of retinopathy in OXYS rats was accompanied by elevated dopamine and DOPAC levels, decreased MAO activity, and changes in the expression of genes associated with the dopaminergic synapse signaling.},
}

Animals
*Retina/metabolism/pathology
Rats
*Aging/metabolism
*Macular Degeneration/metabolism/pathology
Rats, Wistar
Monoamine Oxidase/metabolism
*Biogenic Monoamines/metabolism
Male
Dopamine/metabolism
Tyrosine 3-Monooxygenase/metabolism

@article {pmid42669560,
year = {2026},
author = {Yakovleva, MA and Kostyukov, AA and Aronshtam, NL and Shilkrot, PM and Borzenok, SA and Kuzmin, VA and Feldman, TB and Dontsov, AE and Ostrovsky, MA},
title = {Age-Related Changes in bis-Retinoids of Lipofuscin Granules in Human Retinal Pigment Epithelium Cells.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {8},
pages = {1417-1431},
doi = {10.1134/S0006297926600985},
pmid = {42669560},
issn = {1608-3040},
mesh = {Humans ; *Lipofuscin/metabolism/chemistry ; *Retinal Pigment Epithelium/metabolism/cytology ; *Retinoids/metabolism/chemistry ; *Aging/metabolism ; Oxidation-Reduction ; Spectrometry, Fluorescence ; },
abstract = {Lipofuscin granules (LGs) in retinal pigment epithelium (RPE) cells contain bis-retinoids and their oxidation and degradation products, rendering them photo- and cytotoxic to intracellular structures. LGs are implicated in the pathogenesis of multiple visual pathologies, including age-related macular degeneration (AMD). They exhibit strong autofluorescence, which has led to the development of fundus autofluorescence (FAF) imaging as a non-invasive diagnostic method in ophthalmology. Spectral analysis of autofluorescence can expand the capabilities of this method, including for preclinical diagnostics, as pathological conditions are often associated with increased proportions of oxidized bis-retinoid derivatives that alter LG autofluorescence parameters. However, limited knowledge of age-dependent changes in LG bis-retinoid composition remains a key limitation. In this study, we combined fluorescence spectroscopy, confocal fluorescence microscopy, and fluorescence lifetime imaging (time-correlated single-photon counting) to demonstrate that, under physiological conditions, aging is accompanied by a progressive increase in the relative abundance of oxidation and degradation products of bis-retinoids in LGs. These findings provide an age-dependent baseline for distinguishing physiological and pathological states, thereby improving the potential of FAF imaging for early (preclinical) diagnosis.},
}

Humans
*Lipofuscin/metabolism/chemistry
*Retinal Pigment Epithelium/metabolism/cytology
*Retinoids/metabolism/chemistry
*Aging/metabolism
Oxidation-Reduction
Spectrometry, Fluorescence

@article {pmid42671233,
year = {2026},
author = {Rosito, A and Caranti, S and Verna, R},
title = {Comparison of adverse events of three anti-VEGF drugs for the treatment of age-related macular degeneration.},
journal = {The Malaysian journal of pathology},
volume = {48},
number = {2},
pages = {267-276},
pmid = {42671233},
issn = {0126-8635},
mesh = {Humans ; *Macular Degeneration/drug therapy ; *Angiogenesis Inhibitors/adverse effects/therapeutic use ; *Ranibizumab/adverse effects/therapeutic use ; *Bevacizumab/adverse effects ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Receptors, Vascular Endothelial Growth Factor/therapeutic use ; *Recombinant Fusion Proteins/adverse effects ; Pharmacovigilance ; },
abstract = {Age-related macular degeneration (AMD) is one of the leading causes of irreversible central vision loss among elderly individuals in developed countries. The neovascular form of AMD is currently treated with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents, particularly ranibizumab, aflibercept, and bevacizumab. Although these therapies significantly improve visual outcomes, repeated intravitreal administration requires continuous monitoring of ocular and systemic adverse events. This review compares the safety profiles of the three principal anti-VEGF agents used for AMD treatment through analysis of pharmacovigilance data, regulatory reports, and major clinical trials. Particular attention is dedicated to ocular complications, systemic thromboembolic events, and the implications of off-label bevacizumab use. Current evidence suggests an overall comparable efficacy and safety profile among the three agents, although Bevacizumab requires stricter preparation and monitoring protocols because of its off-label use. Pharmacovigilance remains essential for identifying safety signals, supporting regulatory decisions, and optimising therapeutic strategies in ophthalmology.},
}

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

@article {pmid42671884,
year = {2026},
author = {Karaca, I and Tezel, TH},
title = {Systemic Lupus Erythematosus Associated Drusen-like Deposits.},
journal = {Retina (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {},
doi = {10.1097/IAE.0000000000005005},
pmid = {42671884},
issn = {1539-2864},
}

@article {pmid42672000,
year = {2026},
author = {Forouhari, A and Cheung, CMG and Leng, LL and Gilead, N and Chakravarthy, U and Teo, KYC},
title = {Predicting risk of progression of early to late AMD in the aging eye through imaging and multimodal evaluation: PRIME study protocol.},
journal = {PloS one},
volume = {21},
number = {8},
pages = {e0355953},
pmid = {42672000},
issn = {1932-6203},
mesh = {Humans ; *Macular Degeneration/diagnostic imaging/pathology/diagnosis ; Disease Progression ; Tomography, Optical Coherence ; Female ; Prospective Studies ; Singapore ; Aged ; Male ; Middle Aged ; Longitudinal Studies ; *Multimodal Imaging ; *Aging/pathology ; Visual Acuity ; Risk Factors ; *Eye/diagnostic imaging/pathology ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is a leading cause of vision impairment globally and demonstrates substantial variation regarding progression and clinical subtypes across populations. This paper describes the methodology of our study, designed to establish the natural history of AMD in Asian elderly and to identify predictors of progression from early signs of AMD to late AMD over a 5-year period.

METHODS: This prospective, longitudinal cohort study aims to recruit 1500 participants from community-based cohorts in Singapore, with a follow-up duration of 5 years. Eligible participants are adults aged 55 years or older without severe systemic illness that would preclude participation. At baseline, demographic data and medical history will be collected, and visual acuity will be assessed. A basic imaging protocol including color fundus photography (CFP), optical coherence tomography (OCT), and OCT angiography (OCTA) will be performed. Blood samples will be collected from consenting participants. Images will be graded for early signs of AMD, defined as the presence of pathological findings on CFP, OCT, or OCTA. Participants without early signs of AMD will undergo annual follow-up using the basic imaging protocol. Those with any pathological findings at baseline or during follow-up will undergo an enhanced imaging protocol every 6 months, including ultrawide-field fundus photography, fundus autofluorescence (FAF), OCT, and OCTA. All follow-up visits will be conducted at the Singapore Eye Research Institute (SERI). Multimodal imaging biomarkers will be integrated with clinical, demographic, genetic, and metabolomic data to assess the relative risk of progression and identify potential predictors. The study protocol has been approved by the SingHealth Centralised Institutional Review Board.

DISCUSSION: There is a paucity of data on the progression of AMD and optimal referral thresholds, particularly in Asian populations. This community-based cohort, representative of the general population, will generate one of the largest longitudinal datasets on AMD in Asia and aims to inform future screening strategies. Study registration number: ClinicalTrials.gov Identifier, NCT07653269.},
}

Humans
*Macular Degeneration/diagnostic imaging/pathology/diagnosis
Disease Progression
Tomography, Optical Coherence
Female
Prospective Studies
Singapore
Aged
Male
Middle Aged
Longitudinal Studies
*Multimodal Imaging
*Aging/pathology
Visual Acuity
Risk Factors
*Eye/diagnostic imaging/pathology

@article {pmid42674195,
year = {2026},
author = {Zhang, S and Song, M and Feng, L and Kang, H and Zhao, H and He, J},
title = {Expression, Purification and Antioxidant Activity of Recombinant Human Vascular Endothelial Growth Factor B167 in Escherichia coli.},
journal = {Protein expression and purification},
volume = {},
number = {},
pages = {107001},
doi = {10.1016/j.pep.2026.107001},
pmid = {42674195},
issn = {1096-0279},
abstract = {Age-related macular degeneration (AMD) is a major cause of visual impairment in the elderly, with oxidative stress as its core pathogenesis. Herein, a prokaryotic expression system in Escherichia coli (E. coli) BL21 was developed to yield recombinant human vascular endothelial growth factor B 167(VEGFB167), after systematic optimization of expression and purification parameters, the antioxidant capacity of the target protein was experimentally verified. VEGFB167 was efficiently expressed as inclusion bodies. Following chromatographic purification, the protein purity attained 97% with a concentration of 1.4 mg/mL. Cellular functional assays revealed that VEGFB167 significantly reduced reactive oxygen species, malondialdehyde, and lactate dehydrogenase release, enhanced both superoxide dismutase activity and SOD1/SOD2 gene expression level, inhibited apoptosis, and promoted cell proliferation. These results support further development of VEGFB167 as a biotherapeutic candidate for oxidative injury-triggered illnesses exemplified by AMD.},
}

@article {pmid42674309,
year = {2026},
author = {Sekáč, D and Faura, G and Eikenes, M and Josifovska, N and Petrovski, G and Ellederová, Z and Eide, L},
title = {Polarized Secretion of Mitochondrial DNA by Retinal Pigment Epithelial cells.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111225},
doi = {10.1016/j.exer.2026.111225},
pmid = {42674309},
issn = {1096-0007},
abstract = {Mitochondrial DNA (mtDNA) damage is strongly implicated in age-related macular degeneration (AMD), the most frequent cause of age-mediated visual impairment in developed countries. Here, we investigated and compared the fate of acutely induced oxidation damage in primary retinal pigment epithelial (RPE) cells. The individual RPE clones responded heterogeneously to hydrogen peroxide, both with respect to cell sensitivity and mtDNA damage formation. Peroxide-induced mtDNA damage in human RPE (hRPE) was fully repaired within 4 hours. In parallel, hRPE cells secreted mtDNA from both apical and basolateral surfaces (AP-mtDNA and BL-mtDNA, respectively) independent of peroxide exposure and that could not be explained by detached cells. Most mtDNA was released apically, and the quality of AP-mtDNA was comparable to that of intracellular mtDNA (c-mtDNA). In contrast, BL-mtDNA constituted only 3% of AP-mtDNA, and exhibited a 10-fold higher damage burden. The difference in mtDNA quality suggests a non-random selection of mtDNA molecules to be targeted for export in apical versus basolateral direction. To investigate this, we analyzed epigenetic marks (m.545 methylation) and SNPs (heteroplasmies) in extracellular and cellular mtDNA. We detected differences Extracellular mtDNA in general appeared to be more modified than c-mtDNA and that AP-mtDNA differs from BL-mtDNA, which is indicative of a targeted secretion. Porcine RPEs (pRPEs) from a minipig model of Huntington's Disease associated with impaired epithelial polarity (TgHD) displayed approximately 2-fold higher leakage of AP-mtDNA than control pRPEs, but lower than hRPEs. Together, our data imply that extracellular mtDNA originating from RPE shapes the outer retina and the implications for polar secretion are discussed.},
}

@article {pmid42675158,
year = {2026},
author = {Chen, KY and Chan, HC and Chan, CM},
title = {Ocular gene therapy targeting retinal angiogenesis and vascular leakage: translational and clinical evidence from a systematic review and meta-analysis.},
journal = {Angiogenesis},
volume = {29},
number = {4},
pages = {},
pmid = {42675158},
issn = {1573-7209},
mesh = {Humans ; *Genetic Therapy/methods ; Animals ; *Retinal Neovascularization/therapy/genetics/metabolism ; *Capillary Permeability ; Translational Research, Biomedical ; Gene Therapy Agents ; },
abstract = {INTRODUCTION: Retinal diseases driven by pathological angiogenesis and vascular leakage, including neovascular age-related macular degeneration and diabetic retinopathy, impose substantial visual and treatment burdens because current anti-vascular endothelial growth factor (anti-VEGF) therapy requires repeated intravitreal administration. Ocular gene therapy can provide durable intraocular expression of therapeutic proteins and sustained pathway-level disease control.

METHODS: This systematic review and meta-analysis was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO) and conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. PubMed, Scopus, Web of Science, ScienceDirect, and the Cochrane Library were searched from inception to April 21, 2026. Eligible studies included preclinical, in vitro, and clinical investigations of gene-based interventions targeting retinal angiogenesis, vascular permeability, or related anatomical and treatment-burden outcomes. Random-effects meta-analyses were performed using standardized mean differences (SMDs), mean differences (MDs), and logit event rates.

RESULTS: Twenty-five studies were included. Preclinical gene therapy significantly reduced pathological neovascularization, with a pooled standardized mean difference (SMD) of -1.16 (95% confidence interval [CI], -1.48 to -0.84; p < 0.001) and negligible heterogeneity (I² = 0%). Vascular leakage was also significantly reduced across preclinical experimental studies, with a pooled mean difference (MD) of 0.215 (95% CI, 0.178-0.251; p < 0.001; I[2] = 0%) after directional harmonization. In clinical cohorts, ocular gene therapy significantly reduced central subfield thickness (CST) by -55.30 μm (95% CI, -72.58 to -38.03; p < 0.001) and was associated with reduced anti-vascular endothelial growth factor (anti-VEGF) treatment burden, with a pooled logit event rate of 0.62 (95% CI, 0.20-1.04; p = 0.0039), corresponding to a pooled proportion of approximately 65% of participants meeting study-specific criteria for reduced supplemental anti-VEGF use.

CONCLUSION: Ocular gene therapy shows strong preclinical anti-angiogenic and anti-permeability effects, with emerging clinical evidence of anatomical improvement and reduced anti-VEGF treatment burden in neovascular retinal disease cohorts. Larger disease-specific randomized trials are required to confirm long-term efficacy, safety, and patient selection.},
}

Humans
*Genetic Therapy/methods
Animals
*Retinal Neovascularization/therapy/genetics/metabolism
*Capillary Permeability
Translational Research, Biomedical
Gene Therapy Agents

@article {pmid42675195,
year = {2026},
author = {Mendo, I and Camacho, P and Cabral, D},
title = {Incidental subfoveal choroidal synphlebia in non-neovascular age-related macular degeneration.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42675195},
issn = {1476-5454},
}

@article {pmid42675470,
year = {2026},
author = {Hazra, D and Tomita, Y and Uchida, A and Kato, S and Nagai, N and Suzuki, M and Minami, S and Kunimi, H and Ban, N and Kurihara, T and Shinoda, H and Ozawa, Y and Negishi, K},
title = {Long-term visual outcomes and development of retinal pigment epithelial and outer retinal atrophy in neovascular age-related macular degeneration: a comparison of conventional and novel classifications.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {42675470},
issn = {1471-2415},
support = {23K15938 and 25K12855//Japan Society for the Promotion of Science/ ; },
mesh = {Humans ; *Retinal Pigment Epithelium/pathology ; *Visual Acuity/physiology ; Female ; Tomography, Optical Coherence/methods ; Male ; Atrophy ; Aged ; Fluorescein Angiography/methods ; *Wet Macular Degeneration/drug therapy/classification/physiopathology/diagnosis ; Angiogenesis Inhibitors/therapeutic use ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Retrospective Studies ; Intravitreal Injections ; Polypoidal Choroidal Vasculopathy ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Retinal Photoreceptor Cell Outer Segment/pathology ; },
abstract = {BACKGROUND: Retinal pigment epithelial and outer retinal atrophy (RORA) and complete RORA (cRORA) are major determinants of long-term vision in neovascular age-related macular degeneration (nAMD), but their development across subtypes is poorly defined, especially in Asian populations, in whom pachychoroid-driven disease is common. We compared long-term visual outcomes and atrophy burden between the conventional and novel nAMD classifications.

METHODS: One hundred twenty eyes of 120 treatment-naïve patients with nAMD followed at least six years were classified by conventional (typical nAMD [tAMD], polypoidal choroidal vasculopathy [PCV], retinal angiomatous proliferation [RAP]) and novel (drusen type, pachychoroid type, mixed type, other type) schemes. All eyes received three loading anti-VEGF injections followed by a pro re nata regimen. RORA within the central 1 mm was graded on optical coherence tomography; lesions ≥ 250 μm were defined as cRORA. Visual acuity (VA) retention, atrophy prevalence, and VA around atrophy onset were assessed.

RESULTS: Mean age was 78.0 ± 9.2 years and overall VA retention was 71%. VA retention did not differ among conventional subtypes, but under the novel classification was significantly lower in the drusen type and higher in the pachychoroid type (P < 0.01). VA declined significantly after both RORA and cRORA onset (both P < 0.001). Final RORA/cRORA prevalence was 44.4%/29.6% in tAMD, 50.0%/28.3% in PCV, 83.3%/50.0% in RAP and 76.9%/61.5% in the drusen type, in which cRORA was highest (P < 0.05).

CONCLUSIONS: The novel classification distinguished long-term visual outcomes that the conventional classification did not: the drusen type showed the poorest VA retention and highest cRORA prevalence, whereas the pachychoroid type fared best.},
}

Humans
*Retinal Pigment Epithelium/pathology
*Visual Acuity/physiology
Female
Tomography, Optical Coherence/methods
Male
Atrophy
Aged
Fluorescein Angiography/methods
*Wet Macular Degeneration/drug therapy/classification/physiopathology/diagnosis
Angiogenesis Inhibitors/therapeutic use
Aged, 80 and over
Fundus Oculi
Follow-Up Studies
Retrospective Studies
Intravitreal Injections
Polypoidal Choroidal Vasculopathy
Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Retinal Photoreceptor Cell Outer Segment/pathology

@article {pmid42667403,
year = {2026},
author = {Hasegawa, T and Yagi, R and Fujita, H and Nishimaki, R and Asami, H and Orio, Y and Hiranuma, Y and Saima, Y and Taguchi, R and Tanaka, Y and Kaburaki, T and Kakehashi, A and Nakagawa, S},
title = {Bilateral choroidal thinning during unilateral aflibercept for neovascular age-related macular degeneration: 5-year mixed-effects analysis.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42667403},
issn = {1435-702X},
support = {24K12750//Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS)/ ; 25K12854//Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (JSPS)/ ; },
abstract = {PURPOSE: To evaluate 5-year choroidal changes in eyes with unilateral neovascular age-related macular degeneration (nAMD) treated with intravitreal aflibercept (IVA) and to compare longitudinal changes among treated, fellow untreated, and control eyes using mixed-effects modeling.

METHODS: Sixteen patients with unilateral nAMD (16 treated and 16 fellow untreated eyes) and 20 age-matched and sex-matched control eyes were included. Best-corrected visual acuity (BCVA), central subfield thickness (CST), central choroidal thickness (CCT), and choroidal vascularity index (CVI) were assessed. Absolute and proportional CCT changes were analyzed. Annual rates of change were estimated using linear mixed-effects models.

RESULTS: Over 5 years, control eyes showed mild age-related choroidal thinning (- 3.7 μm/year). In contrast, CCT declined significantly faster in treated eyes (- 11.5 μm/year; p < 0.01 vs. control); fellow untreated eyes also demonstrated accelerated thinning (- 8.2 μm/year; p < 0.05 vs. control). Proportional analyses showed a similar graded pattern. BCVA worsened and CST decreased in treated eyes, while remaining stable in fellow eyes. CVI increased modestly and similarly in treated and fellow eyes (approximately + 0.8%/year).

CONCLUSION: In this 5-year three-group longitudinal analysis, treated eyes showed the greatest annual reduction in CCT, fellow untreated eyes showed an intermediate reduction, and age-matched control eyes showed the smallest decline. The inclusion of a control group indicated that fellow-eye thinning exceeded that expected from physiological aging alone, supporting bilateral choroidal change during long-term unilateral IVA therapy.},
}

@article {pmid42668221,
year = {2026},
author = {Holt, C and Neidert, C and Gedtal, M and Virgili, G and Hogg, R and Qureshi, R},
title = {Corrigendum to "Prognostic factors for age-related macular degeneration progression: An overview of systematic reviews" [Surv Ophthalmol 71(3) (2025): 759-773].},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.08.010},
pmid = {42668221},
issn = {1879-3304},
}

@article {pmid42668661,
year = {2026},
author = {Beqiri, S and Herrera, G and Shen, M and Berni, A and El-Mulki, OS and Badla, O and Lam, W and Herrera, E and Ascioti, N and Moxam, J and Shuldiner, S and Boopathiraj, N and Cheng, Y and Le, VH and Trivizki, O and O'Brien, RC and Wang, RK and Gregori, G and Rosenfeld, PJ},
title = {Symmetry in the Enlargement Rates of Large Hypertransmission Defects between Eyes in Age-Related Macular Degeneration.},
journal = {Ophthalmology science},
volume = {6},
number = {10},
pages = {101333},
pmid = {42668661},
issn = {2666-9145},
abstract = {PURPOSE: The symmetry of macular atrophy growth rates between eyes of patients with bilateral nonexudative age-related macular degeneration (AMD) was assessed to determine if both eyes could be used in clinical trials to test therapies that might slow the growth of atrophy.

DESIGN: Retrospective review of prospectively collected swept-source OCT angiography images.

SUBJECTS: Patients with bilateral nonexudative AMD with ≥1 large hypertransmission defect (hyperTD) in both eyes were included.

METHODS: All large hyperTDs, defined by a greatest linear dimension ≥250 μm, were identified by 2 independent graders and annotated using a semiautomated algorithm. Growth rates were assessed using the area, square root (sqrt) area, and the perimeter-adjusted growth-rate strategies. Baseline lesion sizes were stratified using a size breakpoint of 0.9 disc area (DA). Intereye comparisons of annual hyperTD growth rates were performed. Power analyses were calculated to determine the sample sizes needed for different clinical trial designs.

MAIN OUTCOME MEASURES: Intereye concordance of growth rates was evaluated using Lin concordance correlation coefficients, and inter eye growth-rate agreement was evaluated using Bland-Altman analyses. Sample sizes for a 2-arm clinical trial design were calculated to detect a 30% reduction in growth rates in the treatment arm with 80% power and a 2-sided α = 0.05.

RESULTS: Sixty-four subjects (128 eyes) were followed for a mean of 4.2 ± 1.9 years, providing 942 annualized growth-rate intervals. Prior to stratification by baseline size of 0.9 DA, intereye concordance was high (rc = 0.76) for the total area growth rate, but lower for the sqrt and perimeter-adjusted growth rates (rc = 0.51, rc = 0.60, respectively). Upon stratification, lesions <0.9 DA showed low correlation (0.39-0.46) across the 3 growth rates, but lesions ≥0.9 DA showed high correlation regardless of the transformation strategy (0.73-0.78).

CONCLUSIONS: High intereye concordance in hyperTD growth rates was observed for lesions ≥0.9 DA using 3 different growth-rate strategies. Regardless of the growth-rate strategy used, recruitment of fellow eyes in a paired-eye study for localized treatments or both eyes for systemic treatments resulted in a marked reduction in sample sizes, with improved clinical trial efficiency.

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

@article {pmid42668898,
year = {2026},
author = {Kurzawa-Akanbi, M and Haggarty, J and Hansohn, C and Patel, MT and Cree, AJ and Teo, P and Armstrong, M and Coles, N and Platt, M and Griffiths, H and Cordell, HJ and Khundakar, A and Goldberg Oppenheimer, P and Whitfield, P and Lotery, A and Urlaub, H and Mozaffari-Jovin, S and Lako, M},
title = {Systematic Analysis of Plasma-Derived Extracellular Vesicle-Enriched Samples in Age-Related Macular Degeneration Reveals Oxidative Stress Linked to Altered Lipid and Protein Profiles.},
journal = {Journal of extracellular biology},
volume = {5},
number = {9},
pages = {e70178},
pmid = {42668898},
issn = {2768-2811},
abstract = {Vision impairment caused by age-related macular degeneration (AMD) is a global health priority. Retinal pathology is driven by ageing and exacerbated by genetic and environmental risk factors. Peripheral blood circulation is increasingly recognised as a contributor to disease initiation and progression, and a source of biomarkers to support earlier diagnosis and personalised treatment strategies. Here, we performed an analysis of plasma-derived extracellular vesicle (EV)-enriched samples from 30 AMD and 30 controls. Proteomics identified significantly altered proteins in AMD, the majority of which were downregulated with a strong interaction network involving complement proteins and endopeptidase inhibitors. Importantly, many of the altered proteins are known AMD biomarker candidates and act in pathways affecting AMD: oxidative stress response, immune function and proteolysis dysregulation. Lipidomics revealed an increase in total sphingomyelin to ceramide ratio in AMD, indicating lipid metabolism defects. Raman spectroscopy complemented these findings by demonstrating protein and lipid oxidative modifications, alongside compositional abnormalities in AMD samples. Thus, AMD plasma EV-enriched samples carry a systemic signature of complement and coagulation dysregulation, impaired redox homeostasis, and altered sphingolipid metabolism, reflecting established mechanisms of AMD retinal pathology. These AMD-associated biochemical profiles form a promising source for developing new diagnostics and mechanistic insights for precision medicine.},
}

@article {pmid42669558,
year = {2026},
author = {Pavlenko, TA and Chesnokova, NB and Lisovskaya, OA and Beznos, OV and Grigoryev, AV},
title = {Neuroprotective Effect of Subconjunctival Melatonin Injections in 6-Hydroxydopamine-Induced Neurotoxic Eye Damage.},
journal = {Biochemistry. Biokhimiia},
volume = {91},
number = {8},
pages = {1396-1405},
doi = {10.1134/S0006297925603880},
pmid = {42669558},
issn = {1608-3040},
mesh = {Animals ; *Melatonin/administration & dosage/pharmacology/therapeutic use ; Rabbits ; *Neuroprotective Agents/administration & dosage/pharmacology ; *Oxidopamine/toxicity ; Matrix Metalloproteinase 9/metabolism ; Male ; Retina/drug effects/metabolism/pathology ; Vitreous Body/metabolism/drug effects ; alpha-Macroglobulins/metabolism ; Intraocular Pressure/drug effects ; },
abstract = {The search for new effective methods of neuroprotection is relevant for the treatment of a wide range of common eye diseases such as age-related macular degeneration, glaucoma, and diabetic retinopathy. Using a rabbit model of neurotoxic eye damage induced by intravitreal injection of the dopaminergic neurotoxin 6-hydroxydopamine (6-OHDA), we studied the effect of subconjunctival injections of 0.1% melatonin solution on pathophysiological and biochemical processes in the eye. Administration of 6-OHDA caused destruction of the retinal pigment epithelium, narrowing of retinal vessels, hemorrhages, decrease in ocular blood flow, and intraocular pressure, as well as reduced activity of α2-macroglobulin and concentrations of matrix metalloproteinase-9 and angiotensin-converting enzyme in the aqueous humor, vitreous body, and retina. Subconjunctival melatonin injections over 9 days resulted in the 2-fold on average reduction of the area of retinal damage, and normalization of the minute volume of ocular blood flow and intraocular pressure. On day 14, an increase in the α2-macroglobulin activity in the aqueous humor (0.66 ± 0.19 vs. 0.49 ± 0.13 nmol/min per 1 mg protein) and vitreous body (0.50 ± 0.15 vs. 0.21 ± 0.07 nmol/min per 1 mg protein, p < 0.05) was observed, along with a decrease in the matrix metalloproteinase-9 concentration (118.4 ± 34.6 vs. 524.3 ± 163.2 ng/mg, p < 0.05) and angiotensin-converting enzyme concentration (371.0 ± 52.1 vs. 596.1 ± 171.5 ng/mg, p < 0.05) in the retina. This indicates reduction in the intensity of inflammation and vascular wall permeability. Melatonin could be considered a promising neuroprotective component in the complex therapy of retinal diseases.},
}

Animals
*Melatonin/administration & dosage/pharmacology/therapeutic use
Rabbits
*Neuroprotective Agents/administration & dosage/pharmacology
*Oxidopamine/toxicity
Matrix Metalloproteinase 9/metabolism
Male
Retina/drug effects/metabolism/pathology
Vitreous Body/metabolism/drug effects
alpha-Macroglobulins/metabolism
Intraocular Pressure/drug effects