@article {pmid42135020,
year = {2026},
author = {Ferro Desideri, L and Scandella, D and Anguita, R and Schmitz-Valckenberg, S and Chakravarthy, U and Holz, FG and Querques, G and Wolf, S and Sznitman, R and Zinkernagel, M},
title = {Assessing intergrader variability in incomplete outer retinal atrophy (iRORA) grading.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328470},
pmid = {42135020},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: To assess the intergrader variability in detecting incomplete outer retinal atrophy (iRORA), an optical coherence tomography (OCT) biomarker for early atrophic changes in age-related macular degeneration (AMD) and a potential clinical trial endpoint.

METHODS: We performed a cross-sectional intergrader agreement study using 60 OCT B-scans enriched for iRORA features from non-exudative AMD eyes. Five international retinal experts independently graded images for iRORA presence according to the current Classification of Atrophy Meeting (CAM) criteria, using a standardised online annotation platform. Pairwise agreement was assessed with Cohen's Kappa; agreement with the majority vote, sensitivity and specificity were calculated using a leave-one-out approach. Annotation lead times were recorded to explore links between decision speed and grading consistency.

RESULTS: Mean pairwise Cohen's Kappa was 0.425 (range 0.19-0.73), indicating mild agreement. Agreement with the majority vote ranged from κ=0.48 to 0.67, with classification accuracy between 0.73 and 0.83. Sensitivity varied from 0.59 to 0.83, while specificity remained high (0.85-0.96). Annotation lead times were generally shorter when grader decisions aligned with the majority consensus.

CONCLUSION: Despite standardised CAM definitions, intergrader reproducibility for iRORA detection remains limited, reflecting challenges in consistent early atrophy identification. Refinement of grading guidelines and integration of automated detection systems could improve reliability for AMD clinical trials and clinical practice.},
}

@article {pmid42135021,
year = {2026},
author = {Romano, F and Stettler, I and Finn, M and Vingopoulos, F and Ding, X and Overbey, K and Cort, T and Chen, C and Ploumi, I and Baldwin, G and Zhu, Y and Nodecker, KN and Gumustop, SS and Shah, SH and Laíns, I and Kim, L and Vavvas, D and Husain, D and Miller, JW and Miller, JB},
title = {Multimodal imaging determinants of contrast sensitivity loss in geographic atrophy.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329036},
pmid = {42135021},
issn = {1468-2079},
abstract = {AIMS: To investigate associations between imaging biomarkers and quantitative contrast sensitivity (CS) function (qCSF) metrics in geographic atrophy (GA).

METHODS: Cross-sectional study including 97 eyes from 70 patients (>55 years) with GA within 1500 µm of the fovea and visual acuity (VA)>20/320. Participants underwent VA and qCSF testing (area under the log CS function (AULCSF), contrast acuity (CA), and CS at 1-18 cycles per degree (cpd)) and multimodal imaging with blue autofluorescence (BAF), optical coherence tomography (OCT), and, in 55 eyes, swept-source OCT angiography (SS-OCTA). Imaging biomarkers included GA size, prior growth rate, configuration, BAF pattern, circularity, percentage of foveal involvement (%FI), foveal distance and macular inner choroid flow deficit percentage (mICFD%). Generalised linear mixed-effects and random forest (GRF) models evaluated structure-function relationships.

RESULTS: Participants (age 78.8±5.6 years; 70% female) had a median GA size of 4.0 mm², with 64% showing subfoveal involvement. Larger GA size and higher %FI were significantly associated with worse VA, AULCSF, CA and CS at 1-12 cpd (all p<0.01). Unifocal lesions correlated with lower VA and CS at 6 cpd, while diffuse/banded BAF patterns and greater mICFD% were linked to reduced CS at 1-1.5 cpd. GRF analysis identified GA size and %FI as primary predictors of CS loss, with best performance for AULCSF and CS at 3 cpd (R²=0.319, 0.314).

CONCLUSIONS: GA size and %FI are key determinants of CS loss in GA. qCSF outperformed VA in predictive accuracy, supporting its use as a sensitive functional endpoint in GA trials.},
}

@article {pmid42135289,
year = {2026},
author = {Zhang, C and Wu, J and Shen, X and Liu, Y and He, J and Zheng, X and Ding, W and Li, Z and Zhu, Y and Xu, Z and Su, W and Liu, X and Zhuo, Y},
title = {Metal ions in aging and ocular diseases: biology, pathophysiology, and therapeutic strategies.},
journal = {npj aging},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41514-026-00396-4},
pmid = {42135289},
issn = {2731-6068},
support = {2021HXFH026//Clinical Research Incubation Project, West China Hospital, Sichuan University/ ; 23JZH039//Aier Ophthalmology-Sichuan University Scientific Research Fund Project/ ; 82501266//National Natural Science Foundation of China/ ; 82471074//National Natural Science Foundation of China/ ; BX20240440//China National Postdoctoral Program for Innovative Talents/ ; 2025M772142//China Postdoctoral Science Foundation/ ; 2025QNJS18//Research Funds of the State Key Laboratory of Ophthalmology/ ; 2024A1515013058//Guangdong Basic and Applied Basic Research Foundation/ ; 202206080005//Science and Technology Program of Guangzhou, China/ ; },
abstract = {Metal ions are indispensable for sustaining normal cellular functions and preserving tissue integrity, as they participate in enzymatic catalysis, signal transduction, and antioxidant defense. However, dysregulation of metal ion homeostasis, particularly during aging, disrupts cellular balance and significantly drives the development and progression of age-related ocular diseases, including age-related macular degeneration, glaucoma, diabetic retinopathy, and cataracts. Specifically, metal ions modulate key stress responses that are central to aging and ocular pathogenesis. Excessive accumulation of redox-active metals triggers the generation of reactive oxygen species that induce oxidative damage to lipids, proteins, and DNA. Meanwhile, deficiencies in essential metals, such as iron, zinc, copper, and calcium, impair antioxidant enzyme activity and disrupt DNA repair, exacerbating cellular dysfunction and senescence. The therapeutic potential of these metal chelators and antioxidants in restoring their balance, alleviating oxidative stress, and slowing the progression of age-related ocular diseases has been well documented. A deeper understanding of how metal ions influence these processes is crucial for developing more targeted and effective treatments. This article systematically reviews the roles of metal ions in age-related ocular diseases, with a focus on their effects on stress responses and potential therapeutic strategies.},
}

@article {pmid42137658,
year = {2026},
author = {Istanaksai, A and Jama, K and Hammadieh, T and Ali, A and Siddiqui, E and Azizi, S},
title = {The Effect of Nutrition on Dry Age-Related Macular Degeneration: A Systematic Narrative Review of Evidence and Clinical Implications.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106966},
pmid = {42137658},
issn = {2168-8184},
abstract = {Age-related macular degeneration (AMD) is a progressive retinal condition characterised by degeneration of the macula, leading to central vision loss. Whilst the underlying mechanism of AMD is not fully understood, oxidative stress is believed to be the main driving force behind retinal damage. Although the prevalence of AMD increases with factors such as age, smoking, and sun exposure, these alone do not fully explain individual risk. Nutritional factors, in particular dietary antioxidant intake, have been shown to influence the progression of dry AMD by mitigating oxidative stress and supporting retinal cellular function. By considering the effects of nutrition on retinal health and disease outcomes, we can further our understanding of AMD pathogenesis.},
}

@article {pmid42138517,
year = {2026},
author = {Chen, R and Lu, W and Zhu, J and Huang, L and Chen, W and Huang, G and Ren, X and Sun, Q and Hu, J and Li, J and Wang, S and Kuang, H and Lee, C and Lu, W and Xiong, Z and Liu, Y and Wang, X and Prodeus, A and Zhu, X and Zhang, Q and Li, K and Deng, A and Cao, Y and Yao, Y and Gariepy, J and Liu, X and Yang, Z and Jiang, Q and Li, X},
title = {An Inhibitory Aptamer Against PDGF-C Overcomes Anti-VEGF Refractoriness and Reduces Choroidal Neovascularization and Fibrosis.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {36},
doi = {10.1167/iovs.67.5.36},
pmid = {42138517},
issn = {1552-5783},
mesh = {*Choroidal Neovascularization/metabolism/drug therapy/pathology/prevention & control ; Animals ; *Aptamers, Nucleotide/pharmacology/therapeutic use ; Humans ; Mice ; *Platelet-Derived Growth Factor/antagonists & inhibitors ; Fibrosis/prevention & control ; Disease Models, Animal ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Lymphokines/antagonists & inhibitors/metabolism ; Cell Proliferation/drug effects ; Mice, Inbred C57BL ; Cell Movement/drug effects ; Cells, Cultured ; Angiogenesis Inhibitors/pharmacology ; Surface Plasmon Resonance ; Fibroblasts/drug effects/metabolism ; Signal Transduction ; *Choroid/pathology ; },
abstract = {PURPOSE: Wet age-related macular degeneration is a leading cause of irreversible vision loss, primarily due to choroidal neovascularization (CNV) and subsequent fibrosis. Although current anti-vascular endothelial growth factor A (anti-VEGF) therapies offer significant benefits, many patients exhibit limited or no response and develop drug resistance over time, necessitating the exploration of complementary or alternative therapeutics. This study aimed to identify and characterize a platelet-derived growth factor-C (PDGF-C)-targeting DNA aptamer and to evaluate its therapeutic potential for suppressing CNV and fibrosis, including in an anti-VEGF-refractory setting.

METHODS: A DNA aptamer against PDGF-C (α-PC aptamer) was identified using systematic evolution of ligands by exponential enrichment. Its binding to PDGF-C and inhibition of PDGF-C/platelet-derived growth factor receptor alpha (PDGFRα) interaction were assessed using surface plasmon resonance. The effects of the α-PC aptamer on PDGF-C-induced proliferation, migration, and PDGFRα, Akt, and extracellular-regulated kinase (ERK) signaling were examined in fibroblasts and human umbilical vein smooth muscle cells (HUVSMCs). In vivo efficacy was evaluated in a laser-induced CNV mouse model, including anti-VEGF refractory aged mice.

RESULTS: The α-PC aptamer specifically bound to PDGF-C and effectively blocked its binding to PDGFRα. The α-PC aptamer significantly inhibited PDGFRα, Akt, and ERK activation and suppressed PDGF-C-induced proliferation and migration of both fibroblasts and HUVSMCs. Importantly, in a laser-induced CNV mouse model, the α-PC aptamer markedly reduced neovascularization and fibrosis; it particularly retained efficacy in suppressing CNV in anti-VEGF refractory aged mice, where anti-VEGF treatment failed to do so.

CONCLUSIONS: These findings suggest that the α-PC aptamer represents a promising therapeutic agent for treating neovascular diseases, especially in patients refractory to anti-VEGF treatment.},
}

*Choroidal Neovascularization/metabolism/drug therapy/pathology/prevention & control
Animals
*Aptamers, Nucleotide/pharmacology/therapeutic use
Humans
Mice
*Platelet-Derived Growth Factor/antagonists & inhibitors
Fibrosis/prevention & control
Disease Models, Animal
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Lymphokines/antagonists & inhibitors/metabolism
Cell Proliferation/drug effects
Mice, Inbred C57BL
Cell Movement/drug effects
Cells, Cultured
Angiogenesis Inhibitors/pharmacology
Surface Plasmon Resonance
Fibroblasts/drug effects/metabolism
Signal Transduction
*Choroid/pathology

@article {pmid42128044,
year = {2026},
author = {Hu, Z and Qi, H and Dong, X and Tian, Y and Sun, M and Jia, X and Yu, H},
title = {Metabolic Reprogramming and Mitochondrial Dynamics: Novel Therapeutic Perspectives for Age-Related Macular Degeneration.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111064},
doi = {10.1016/j.exer.2026.111064},
pmid = {42128044},
issn = {1096-0007},
abstract = {Age-related macular degeneration (AMD) represents the leading cause of irreversible vision loss in the elderly, affecting over 200 million individuals worldwide. Despite recent advances, therapeutic options remain severely limited, particularly for dry AMD characterized by progressive geographic atrophy. Emerging evidence implicates mitochondrial dysfunction and metabolic reprogramming of retinal pigment epithelium (RPE) cells as central pathogenic drivers. Under pathological conditions, RPE cells exhibit profound bioenergetic collapse marked by declining oxidative phosphorylation, compensatory glycolytic activation, and aberrant tricarboxylic acid cycle intermediate accumulation. This metabolic catastrophe is structurally underpinned by dysregulated mitochondrial dynamics. The resultant accumulation of fragmented, dysfunctional mitochondria perpetuates reactive oxygen species overproduction and mitochondrial DNA damage, establishing a self-amplifying vicious cycle driving RPE degeneration. Mechanistically, this involves dysregulation of the AMPK/mTOR energy-sensing axis, SIRT1/PGC-1α transcriptional control, and Nrf2/ARE antioxidant defenses. Multi-omics profiling reveals distinct metabolic signatures. These discoveries have catalyzed mechanism-based interventions. However, translational applications still face many challenges, and the combination of single-cell multi omics and multimodal therapies is expected to play a role.in restoring mitochondrial homeostasis and preserving vision in aging population in the future.},
}

@article {pmid42129346,
year = {2026},
author = {Enzendorfer, ML and Reiter, GS and Bogunović, H and Riedl, S and Mai, J and Schrittwieser, J and Stapf, C and Mares, V and Mihelčič, M and Little, JA and Jaki-Mekjavić, P and Barthelmes, D and Hatz, K and Zarranz-Ventura, J and Creuzot-Garcher, C and Hogg, R and Sadeghipour, A and Schmidt-Erfurth, U and , },
title = {I-SCREEN: Development of an AI-based infrastructure for community-wide screening and prediction of progression in age-related macular degeneration providing accessible shared care.},
journal = {Eye (London, England)},
volume = {},
number = {},
pages = {},
pmid = {42129346},
issn = {1476-5454},
abstract = {OBJECTIVES: This work describes the design and methodological framework of the I-SCREEN project, which aims to develop an artificial intelligence (AI)-based infrastructure utilising optical coherence tomography (OCT) for early detection of AMD and assessment of progression risk.

METHODS: The pan-European project is conducted across clinics and optometry/optician practices in six European countries. I-SCREEN encompasses seven work packages covering community-based AMD identification, clinical follow-up, AI development and project dissemination. Three interconnected clinical studies are carried out by optometry/optician practices (PYRENEES) and ophthalmology clinics (SUDETES and APENNINES).

RESULTS: The PYRENEES study is a prospective, cross-sectional study evaluating the feasibility of detecting subclinical AMD in optometry/optician practices under ophthalmologist supervision via telemedicine. A robust screening network comprising 28 community-based optometry/optician practices and 7 ophthalmology clinics has been established. Patients with suspected non-neovascular AMD are referred to partnered clinics. In the hospital setting, patients with early or intermediate AMD are followed in the longitudinal SUDETES study, while patients with non-foveal geographic atrophy are invited to take part in the APENNINES study. Data obtained inform AI development for community-based AMD detection and monitoring. Predictive modelling will further enable personalised risk assessments.

CONCLUSIONS: I-SCREEN brings together multidisciplinary experts across Europe to establish an AI-driven shared care model for AMD detection and monitoring. By combining high-quality OCT imaging from community practices with longitudinal clinical studies, the initiative provides novel insights into early AMD progression and  establishes a foundation for innovative AI-based detection and prediction throughout the real-world population.},
}

@article {pmid42129509,
year = {2026},
author = {Yamamoto, A and Nakanishi, Y and Ideyama, M and Akada, M and Tamiya, R and Miyata, M and Kido, A and Tamura, H and Ooto, S and Tsujikawa, A and Hata, M},
title = {Experimental and clinical evidence of multilayer retinal damage caused by subretinal hemorrhage in neovascular age-related macular degeneration.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-52680-8},
pmid = {42129509},
issn = {2045-2322},
support = {No. 24K02293//Japan Society for the Promotion of Science/ ; grant JP25gm6510029h0003//Japan Agency for Medical Research and Development/ ; grant M2025006N//BrightFocus Foundation/ ; },
abstract = {Neovascular age-related macular degeneration (AMD) with subretinal hemorrhage (SRH) is associated with a poor visual prognosis. This study investigated the effects of SRH in neovascular AMD on visual function and retinal integrity. An SRH mouse model, established by subretinal injection of autologous blood, exhibited early apoptotic cell death across both outer and inner retinal layers, ultimately resulting in retinal ganglion cell loss and inner retinal thinning. Clinically, we retrospectively reviewed consecutive treatment-naïve neovascular AMD patients who visited Kyoto University Hospital between December 2012 and December 2013. Among 43 eyes from 43 patients, the presence of baseline SRH was independently associated with poorer best-corrected visual acuity at 1 year (β = 0.16, P = 0.03). Eyes with SRH exhibited significant thinning of the ganglion cell complex (GCC) and outer nuclear layer (ONL). Reductions in GCC and ONL thickness were significantly correlated with worse 1-year BCVA (ρ = 0.51, P = 0.02; and ρ = 0.62, P = 0.003, respectively). These findings indicate that SRH induces neuronal damage not only in the outer retina adjacent to the hemorrhage but also in the inner retinal layers, both of which contribute to sustained visual impairment in neovascular AMD.},
}

@article {pmid42130720,
year = {2026},
author = {Ding, L and Xie, B and Lv, J and Zhou, Z and Zhou, X and Wu, K and Zhang, Q and Lu, F and Wang, C and Qu, J and Xiang, L and Chen, Q},
title = {Bemarituzumab Suppresses Choroidal Neovascularization in Mice by Downregulating Melanoma Cell Adhesion Molecule and Yes-Associated Protein 1.},
journal = {ACS pharmacology & translational science},
volume = {9},
number = {5},
pages = {1099-1108},
pmid = {42130720},
issn = {2575-9108},
abstract = {In recent years, some fibroblast growth factors (FGFs) have been reported to be promising therapeutic targets for neovascular age-related macular degeneration (nAMD). Interestingly, we found that the FGFR2b inhibitor bemarituzumab (FPA144) exerts a beneficial effect in a mouse choroidal neovascularization (CNV) model. Our current study aims to uncover the potential molecular mechanism by which FPA144 alleviates CNV. The effect of FPA144 was evaluated in a laser-induced CNV mouse model. Fundus fluorescein angiography (FFA), optical coherence tomography (OCT), and choroidal flat mounts were carried out for the quantitative assessment of CNV. Label-free quantitative proteomics analysis was performed to assess changes in molecular pathways. Primary cultured human umbilical vein endothelial cells (HUVECs) were used for further confirmation of the target pathway in vitro. FFA, OCT, and choroidal flat mounts demonstrate the protective effect of FPA144 in a mouse CNV model. Compared to the control group, the treated group has smaller vascular leakage areas or smaller CNV lesions. Proteomic analyses indicate that the melanoma cell adhesion molecule (MCAM, CD146)-Yes-associated protein 1 (Yap1) pathway may be involved in the effect of FPA144. Immunostaining of choroidal flat mounts and cryosections reveals decreased expression of CD146 and Yap1 in the vascular endothelial cells of the treated animals. Experiments on HUVECs further verify the inhibitory effect of FPA144 on vascular endothelial cells. Our findings demonstrate that FPA144 can efficiently inhibit the development of choroidal neovascularization in mice by downregulating CD146 and Yap1.},
}

@article {pmid42131406,
year = {2026},
author = {Lin, TY and Wang, CY and Chen, L and Huang, SP},
title = {Adaptive immune crosstalk and complement dysregulation in the aging retina.},
journal = {Tzu chi medical journal},
volume = {38},
number = {2},
pages = {145-151},
pmid = {42131406},
issn = {2223-8956},
abstract = {The eye, long viewed as immune-privileged, is now recognized as a dynamic immunological environment where innate and adaptive mechanisms intersect to maintain retinal homeostasis. In aging and age-related retinal diseases such as age-related macular degeneration (AMD), this balance deteriorates as chronic, low-grade inflammation replaces immune quiescence. Adaptive immune involvement in AMD is reflected by increased antiretinal autoantibodies and systemic immune changes, including accelerated aging of CD8[+] T-cells. Complement activation further amplifies adaptive responses; C5a stimulates T-cell secretion of proinflammatory cytokines, such as interleukin-17 (IL-17) and IL-22, which contribute to retinal injury. Retinal cells exhibit context-dependent immune plasticity. Retinal pigment epithelial (RPE) cells upregulate major histocompatibility complex molecules in response to stress and can express the regulatory transcription factor forkhead box p3 (FOXP3), indicating an intrinsic immunomodulatory capacity. Myeloid populations are likewise heterogeneous: Resident microglia maintain immune surveillance, whereas infiltrating monocyte-derived macrophages often drive maladaptive inflammation and lesion progression. The complement system also contributes to age-related synaptic remodeling, with C1q and C3 tagging synapses for elimination. This pathway is normally limited by Complement Factor H (CFH), whose regulatory function is strengthened by binding to apolipoprotein E (APOE). However, the neurodegeneration-associated APOE ε4 isoform shows reduced CFH affinity, promoting excessive complement activity. Sex-specific immune aging further modifies complement signaling, microglial behavior, and APOE-dependent susceptibility. Together, these insights illustrate how adaptive immunity shifts from protective surveillance to chronic, pathological inflammation, driving the initiation and progression of age-related retinal degeneration.},
}

@article {pmid42131590,
year = {2026},
author = {Bao, L and Ying, H and Wang, X and Wu, M and Liu, H},
title = {Subtle outer retinal and choroidal alterations in patients at high risk of progression to age-related macular degeneration.},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1807534},
pmid = {42131590},
issn = {2296-858X},
abstract = {AIM: To explore the changes in the microstructure and blood supply of the outer retina in eyes at high risk of progression to age-related macular degeneration (AMD).

METHODS: Forty-seven patients with unilateral neovascular AMD (nAMD) were enrolled. Twenty-two of the contralateral eyes were considered at high risk of progression to nAMD (Group 1), while the remaining 25 eyes had dry AMD (Group 2) Fifty healthy subjects (50 eyes) were enrolled as control. Swept-source optical coherence tomography (SS-OCT) equipped with angiovue (OCTA) was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary plexuses (SCP and DCP) around the macula and choroid vessel index (CVI). Quantitative analysis was automatically calculated by an inbuilt algorithm in the SS-OCTA (VG200; SVision Imaging, Ltd., Luoyang, China). One-way analysis of variance (ANOVA) was used to compare the differences among the groups, and post hoc procedures were used to compare differences between the two groups. Associations between OCTA-derived parameters and retinal/choroidal thickness were evaluated using Pearson correlation coefficients.

RESULTS: Compared to the controls, the densities of the SCP and DCP were significantly decreased in Group 2 in some regions (p < 0.05). However, the CVI of patients in superior (S) and temporal (T) regions was significantly decreased compared to the controls (P: 0.009, 0.020). The outer retinal thickness of Group 2 in the central (C), S, and temporal (T) regions were significantly decreased compared to the controls and Group 1 (P: 0.004-0.048). Meanwhile, compared to the controls, the thickness of total retina and choroid of Group 2 were significantly decreased in most regions (P: 0.001-0.034). The outer retinal thickness was significantly correlated to choroidal thickness in AMD patients (r = 0.346, p = 0.034).

CONCLUSION: Significant thinning of outer retina and choroid were observed in patients with dry AMD. In eyes at high risk of progression to AMD, choroidal thickness and CVI tend to be decreased. SS-OCTA might be useful in evaluating microstructural and blood supply disorders of the outer retinal layers in healthy eyes of unilateral nAMD patients, which might be helpful to identify the earliest progression of AMD.},
}

@article {pmid42131985,
year = {2026},
author = {Lin, Q and Oh, XY and Owh, C and Sim, B and Ow, V and Wong, JHM and Boo, YJ and Ong, NWX and Truong, VX and Loh, XJ and Lim, JYC},
title = {Visible Light Photo-Cross-Linked Thermogel─A Single-Component Hybrid Supramolecular-Covalent Hydrogel for Sustained Drug Release.},
journal = {ACS applied materials & interfaces},
volume = {},
number = {},
pages = {},
doi = {10.1021/acsami.6c01197},
pmid = {42131985},
issn = {1944-8252},
abstract = {Temperature-responsive supramolecular thermogels, advanced biomaterials that exhibit sol-to-gel phase transitions when warmed, show great promise as next-generation in vivo drug delivery depots for their excellent biocompatibility and ease of formulation and administration. However, the lack of permanent covalent cross-links within the gel framework often results in short in vivo persistence and rapid gel swelling, in turn limiting duration of sustained drug release attainable. Herein, we developed a general strategy that retains the thermogels' intrinsic ease of injectability, yet allowing significantly enhanced sustained drug release durations. By incorporating a visible light-cross-linkable chromophore into the thermogel polymer structure, in situ cross-linking can be achieved after depot administration with facile external control. As compared to conventional photo-cross-linking strategies utilizing ionizing and hazardous UV light, our thermogels can be covalently cured using blue light or even under ambient indoor lighting conditions, making them potentially suitable for sensitive applications such as ophthalmic drug release. We show that these thermogels can be applied as an in situ cross-linked depot that allows the release of the antivascular endothelial growth factor biologic, Aflibercept, to be prolonged for more than 3 months, achieving a marked improvement over existing treatment regimens for diseases such as neovascular age-related macular degeneration that necessitate monthly injections. Additionally, these photo-cross-linked thermogels can also prolong the release of small proteins (e.g., bovine serum albumin) from membrane-based delivery systems by more than 3 times compared to nonirradiated controls. These visible light-photo-cross-linkable gels offer new versatile platforms for achieving long-duration drug release suitable for different biological applications and delivery modalities.},
}

@article {pmid42132121,
year = {2026},
author = {Munk, M and Holz, FG and Chow, D and Sala-Puigdollers, A and Arias, L and Heier, J and Sakamoto, T and Souied, E and Godfrey, J and Douglas, K and Johnson, Z and Treece, T and Yiu, G},
title = {Real-world durability challenges with nAMD treatments and the potential promise of gene therapy.},
journal = {Current medical research and opinion},
volume = {},
number = {},
pages = {1-7},
doi = {10.1080/03007995.2026.2670008},
pmid = {42132121},
issn = {1473-4877},
abstract = {The introduction of anti-vascular endothelial growth factor (VEGF) therapies changed the treatment landscape for neovascular age-related macular degeneration (nAMD), slowing the progression of central vision loss. However, current anti-VEGF therapies are limited by the need for frequent intravitreal injections to maintain disease control, which places a substantial burden on patients, caregivers, and healthcare systems, and contributes to poorer treatment adherence and persistence in the real-world setting. To extend the dosing interval, flexible dosing strategies were implemented; however, they carry the risk of both undertreatment and overtreatment. Emerging longer-acting strategies include continuous-release delivery systems (e.g. ranibizumab port delivery system) and gene therapy. Investigational gene therapies have been designed to preferentially target non-dividing retinal cells, enabling sustained expression of a therapeutic protein for the lifespan of these cells. While the therapeutic effect is designed to persist for years following the one-time administration of gene therapy, early clinical trials show that a subset of patients do receive supplemental anti-VEGF injections. Emerging patterns of retreatment support the concept that supplemental treatment does not necessarily indicate waning efficacy, but rather the adjuvant treatment may be used transiently to fine tune for increased disease activity levels at the patient level. In summary, multiple factors need to be considered to understand the durability of future therapies, not only reduced procedural frequency but also continuous disease control and improved quality of life - key metrics that will guide the evolution of care in nAMD.},
}

@article {pmid42132461,
year = {2026},
author = {Vujosevic, S and Zanzottera, E and Brotto, L and Piccoli, G and Alovisi, C and Bucceri, V and Rui, C and Poletti, E and Brambilla, M and Coppola, M and Nucci, P and Chakravarthy, U},
title = {Spectrally Resolved Fundus Autofluorescence as a Biomarker of Retinal Metabolic Integrity in Intermediate and Atrophic AMD.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {31},
doi = {10.1167/iovs.67.5.31},
pmid = {42132461},
issn = {1552-5783},
mesh = {Humans ; Cross-Sectional Studies ; Male ; Female ; Tomography, Optical Coherence/methods ; Aged ; *Fluorescein Angiography/methods ; *Retinal Pigment Epithelium/pathology/metabolism ; *Geographic Atrophy/metabolism/diagnosis ; Aged, 80 and over ; Fundus Oculi ; Middle Aged ; Biomarkers/metabolism ; Retinal Drusen/metabolism/diagnosis ; *Macular Degeneration/metabolism/diagnosis ; Optical Imaging ; *Retina/metabolism/pathology ; },
abstract = {PURPOSE: To evaluate the association between spectrally resolved fundus autofluorescence (Sr-FAF) signals and four macular lesion types identified on spectral-domain optical coherence tomography (SD-OCT): (1) drusen, (2) incomplete retinal pigment epithelial and outer retinal atrophy (iRORA) and complete retinal pigment epithelium and outer retinal atrophy (cRORA), (3) retinal pigment epithelium (RPE) and outer retinal atrophy, and (4) nascent geographic atrophy (nGA) in eyes with intermediate and atrophic age-related macular degeneration (AMD).

METHODS: This cross-sectional observational study analyzed 775 SD-OCT B-scans from 62 eyes (62 patients) with AMD. Lesions were classified according to established OCT criteria (290 drusen, 49 iRORA, 390 cRORA, 46 nGA). All eyes underwent SD-OCT imaging (97 B-scans) and Sr-FAF using a 450-nm wavelength. Quantitative Sr-FAF metrics (average red emission fluorescence component [REFC] and average green emission fluorescence component [GEFC]) were determined using custom software, and lesion groups were compared via one-way analysis of variance with Scheffé post hoc testing.

RESULTS: Significant differences among lesion types were observed for REFC (F = 59.3, P < 0.001) and GEFC (F = 13.5, P < 0.001). Drusen exhibited higher REFC intensities than iRORA, cRORA, and nGA (all P < 0.001), and higher GEFC intensities than cRORA (P < 0.001) and nGA (P = 0.002). Wavelength (nm) progressively decreased from drusen to iRORA, nGA, and cRORA. Lesion size (in pixels) differed significantly (iRORA < nGA < drusen < cRORA; P < 0.001) and was the strongest predictor (β = -0.31, P < 0.001) in the regression analysis.

CONCLUSIONS: Sr-FAF reveals distinct metabolic signatures across AMD lesion types. Higher fluorophore signals in drusen suggest preserved photoreceptor-RPE activity, whereas reduced signals in cRORA and nGA reflect advanced atrophy. Combined SD-OCT and Sr-FAF may enhance the detection of early atrophic changes and improve AMD risk stratification.},
}

Humans
Cross-Sectional Studies
Male
Female
Tomography, Optical Coherence/methods
Aged
*Fluorescein Angiography/methods
*Retinal Pigment Epithelium/pathology/metabolism
*Geographic Atrophy/metabolism/diagnosis
Aged, 80 and over
Fundus Oculi
Middle Aged
Biomarkers/metabolism
Retinal Drusen/metabolism/diagnosis
*Macular Degeneration/metabolism/diagnosis
Optical Imaging
*Retina/metabolism/pathology

@article {pmid42132463,
year = {2026},
author = {Vallino, V and Porreca, A and Bandello, F and Batlle-Ferrando, S and Bernal-Morales, C and Boscia, F and Breazzano, MP and Bucceri, V and Chaundhary, V and Chhablani, J and Cicinelli, MV and Couturier, A and Dolz-Marco, R and Sadeghi, E and Elkobi, T and Eller, AW and Gallego-Pinazo, R and Cheung, CMG and Kapoor, S and Melgar, S and Montero, J and Peronetti, M and Pignataro, MG and Puligheddu, S and Termite, AC and Viggiano, P and Vujosevic, S and Zarranz-Ventura, J and Zur, D and Reibaldi, M and Borrelli, E},
title = {Peripapillary Choroidal Neovascularization in Adults: Spectrum of Etiologies and Clinical Features.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {29},
doi = {10.1167/iovs.67.5.29},
pmid = {42132463},
issn = {1552-5783},
mesh = {Humans ; Retrospective Studies ; *Choroidal Neovascularization/etiology/diagnosis/drug therapy ; Male ; Female ; Tomography, Optical Coherence/methods ; Fluorescein Angiography/methods ; Visual Acuity/physiology ; Aged ; Middle Aged ; Aged, 80 and over ; Adult ; *Optic Disk/pathology ; Fundus Oculi ; Multimodal Imaging ; Angiogenesis Inhibitors/therapeutic use ; Macular Degeneration/complications/diagnosis ; Indocyanine Green/administration & dosage ; },
abstract = {PURPOSE: To characterize etiologies and clinical-imaging features of peripapillary choroidal neovascularization (CNV) and identify predictors of underlying disease (i.e., including age-related macular degeneration [AMD] vs. non-AMD etiologies) and visual outcomes.

METHODS: This multicenter retrospective case series included 156 eyes of 138 treatment-naïve patients with peripapillary CNV from 12 tertiary centers. Peripapillary CNV was defined as sub-RPE or subretinal neovascularization within one disc diameter of the optic disc. Multimodal imaging (optical coherence tomography [OCT], fluorescein and indocyanine green angiography, and/or OCT angiography) was used to confirm CNV and etiology. Baseline OCT features included CNV type, exudation pattern, foveal involvement, peripapillary location, and distance to the disc. Longitudinal OCT and best-corrected visual acuity (BCVA, logMAR) were analyzed when available. Management followed routine clinical practice with variable administration of anti-VEGF therapy. Regression models and a conditional inference tree assessed predictors of diagnosis and visual outcome.

RESULTS: The most common etiologies were AMD (51.9%), pachychoroid disease (27.6%), and angioid streaks (6.4%). CNV most frequently involved the temporal peripapillary quadrant (84.6%). Aneurysmal type 1 CNV predominated in pachychoroid disease, whereas type 2 CNV was more common in other etiologies. Baseline BCVA was worse in AMD and angioid streaks and was independently associated with underlying disease and foveal involvement. The Conditional Inference Tree associated age >71 years and nonaneurysmal type 1 or type 2 CNV with AMD.

CONCLUSIONS: Peripapillary CNV most commonly arises from AMD and pachychoroid disease. Simple clinical and imaging features can assist etiological classification and visual prognostication in clinical practice.},
}

Humans
Retrospective Studies
*Choroidal Neovascularization/etiology/diagnosis/drug therapy
Male
Female
Tomography, Optical Coherence/methods
Fluorescein Angiography/methods
Visual Acuity/physiology
Aged
Middle Aged
Aged, 80 and over
Adult
*Optic Disk/pathology
Fundus Oculi
Multimodal Imaging
Angiogenesis Inhibitors/therapeutic use
Macular Degeneration/complications/diagnosis
Indocyanine Green/administration & dosage

@article {pmid42133019,
year = {2026},
author = {Ferrucci, M and Lazzeri, G and Pinelli, R and Biagioni, F and Bumah, VV and Giambelluca, MA and Busceti, CL and Lenzi, P and Fornai, F},
title = {Neuronal death and accumulation of lipid droplets and glycogen granules within retinal pigment epithelium under the influence of mTOR and autophagy.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42133019},
issn = {1435-1463},
support = {Ricerca Corrente 2026, IRCCS Neuromed//Ministero della Salute/ ; },
abstract = {In the course of age-related macular degeneration (AMD) the retinal pigment epithelium undergoes a number of cytopathological alterations that are generated by a dysfunction of specific metabolic pathways. In detail, these include lipid and glycogen accumulation along with dismantling of specific proteins from the plasma membrane. In the present study we analyzed whether 3-methyladenine (3-MA), a classic autophagy inhibitor, may reproduce the pathobiochemical and structural alterations occurring in AMD. Different doses of 3-MA produce a loss of cell viability with lipids and glycogen accumulation, which were quantified by ultrastructural morphometry. This was concomitant with displacement and suppression of autophagy-related proteins along with increased activity of mTOR. A dismantling of phenotype-specific proteins composing tight junctions was observed as well. All these alterations were reverted by the phytochemical autophagy stimulator curcumin which was shown to act as a powerful mTOR inhibitor with an efficacy that was like the classic mTOR inhibitor rapamycin. When these compounds activating autophagy/inhibiting mTOR were administered alone, a beneficial effect was observed even in control cells. The occurrence of 3-MA-induced retinal degeneration was found to be associated with a remarkable aggregation of p62 which is reminiscent of central neurodegenerative disorders, and it was fully prevented by curcumin similarly to rapamycin. These protective effects concern cell viability, altered glycogen and lipid accumulation, and ultrastructural alterations. The present work contributes to understanding degeneration in AMD while extending key biochemical steps to neurodegenerative disorders. The use of natural phytochemicals and light-induced by-products may be used for therapeutic purposes.},
}

@article {pmid42133343,
year = {2026},
author = {Jacobs, A and Anselmo, D and McHugh, R and Fernandez-Garcia, I and Fang, C and Lasko, R and Mukherjee, S and Holekamp, N},
title = {Generative Artificial Intelligence-Driven Voice Assistance for Patient Education in Ophthalmology.},
journal = {JAMA ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1001/jamaophthalmol.2026.1307},
pmid = {42133343},
issn = {2168-6173},
}

@article {pmid42134448,
year = {2026},
author = {Rajapakse, D and Fan, J and Daily, D and Dong, L and Peterson, K and Fariss, R and Wistow, G},
title = {A Human Amelotin Transgenic Mouse Model with Calcified Deposits Similar to Those in Dry Age-related Macular Degeneration.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111068},
doi = {10.1016/j.exer.2026.111068},
pmid = {42134448},
issn = {1096-0007},
abstract = {Amelotin (AMTN), a protein involved in enamel formation, is induced in retinal pigment epithelial (RPE) in patients with dry age-related macular degeneration (AMD) and is associated with calcification in drusen. To examine the effects of constitutive expression of human AMTN in RPE we created a transgenic (TG) mouse model that expresses human AMTN specifically in the RPE using the regulatory components of the mouse Rpe65 gene. This led to several AMD-like abnormalities in RPE but did not produce calcified depositions. Reasoning that other aspects of cell stress or damage may be needed for calcification we tested moderate laser injury of the retina in young TG and WT mice. TG mice, but not WT, developed AMTN-dependent deposits containing AMTN, cholesterol, and calcium phosphate/HAP in the laser lesions, reminiscent of deposits seen in dry AMD drusen. While laser lesions in WT mice healed normally, those in TG mice progressed, obliterating adjacent photoreceptors and recruiting microglia. This shows that chronic expression of AMTN can induce pathologies in RPE and that when coupled with injury can form structures similar to calcified drusen. These deposits are associated with increased retinal damage and inflammation. The model presents a system to test possible therapeutic effects of inhibition or suppression of AMTN in RPE in vivo.},
}

@article {pmid42134616,
year = {2026},
author = {Smith, RT and Rosenfeld, PJ},
title = {Cardiovascular Disease and Age-Related Macular Degeneration.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.05.003},
pmid = {42134616},
issn = {1879-1891},
abstract = {PURPOSE: To provide an update on the published associations between cardiovascular disease (CVD) and age-related macular degeneration (AMD).

DESIGN: Evidence-based perspective.

METHODS: Review of literature and experience of authors.

RESULTS: CVD is the leading cause of death worldwide, and AMD is the leading cause of irreversible blindness among the elderly. Both these conditions are associated with hypertension and smoking. Thus, it was expected that patients with CVD might be at higher risk for AMD, and AMD would be closely associated with CVD. However, such a general association has never been shown in dozens of studies. Instead, current evidence suggests that there are associations only between certain subsets of CVD and AMD. A strong association was shown to exist between specific high-risk cardiovascular diseases (HRCVDs) that confer compromised choroidal perfusion and the presence of subretinal drusenoid deposit (SDD), not ordinary soft drusen, which are considered the hallmark of intermediate AMD. We propose that this compromised choroidal perfusion is the underlying mechanism driving the formation of SDDs. We also propose, more generally, that the formation of SDDs result from the disruption of the normal metabolic support between the choriocapillaris and photoreceptors (PRs). We recommend that HRCVDs need to be studied in association with genetic risk-alleles to better understand the association between decreased choroidal perfusion and AMD progression.

CONCLUSION: The strong association between SDDs to HRCVDs merits further investigation, especially in cardiovascular patients with SDDs carrying the high-risk alleles for AMD. Further prospective studies in both HRCVD and AMD patients are needed to elucidate the totality of clinical and genetic factors that drive AMD. These disease models can then be deployed to identify vasculopathic patients who need a retinal referral for AMD as well as AMD patients who need a cardiovascular workup to address undetected HRCVDs in patients with SDDs.},
}

@article {pmid42134650,
year = {2026},
author = {Jonas, JB and Jonas, RA and Bikbov, MM and Kazakbaeva, GM and Dong, L and Wang, YX and Panda-Jonas, S},
title = {Mechanism of myopic axial Elongation related to Bruch´s membrane.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100329},
doi = {10.1016/j.apjo.2026.100329},
pmid = {42134650},
issn = {2162-0989},
abstract = {PURPOSE: The process of myopic axial elongation has not been fully uncovered yet. Here we propose a Bruch´s membrane (BM)-related hypothesis und present anatomical and clinical findings supporting it.

METHODS: The hypothesis is that ocular axial elongation beyond the age of 3 years occurs by a retina-triggered annular segmental growth of BM in the posterior fundus midperiphery between approximately 10° to 80° anterior to the posterior pole, with a maximum growth at approximately 25° anterior to the posterior pole.

RESULTS: The location of the posterior midperiphery is supported by anatomical findings of an axial length-related thinning of retinal layers, sclera, and retinal pigment epithelium in the posterior midperiphery, the location of pathologic changes at the anterior and posterior border of the BM growth zone (patchy atrophies, parapapillary myopia beta zone and gamma zone, optic nerve head canal widening, cobble stones), and results of clinical trials on myopia prevention in adolescents by circular progressive contact lenses or glasses. The notion of BM as compared to sclera as the primary structure elongating the eye is supported by the axial length-related choroidal thinning most marked at the posterior pole, the axial length-related increase in BM volume, the axial length-related shift of BM-opening of the ONHC into the macular direction, the biomechanical properties of BM, and by primarily not involving the retina, RPE and choriocapillaris in the foveal region.

CONCLUSIONS: If BM is the primary effector structure for axial elongation, future research may address the retinal messenger molecule directing the RPE to locally produce BM.},
}

@article {pmid42134759,
year = {2026},
author = {Kashihara, T and Akiyama, Y and Morita, A and Deguchi, S and Odaka, R and Nakahara, T},
title = {Characterization of mitochondrial dysfunction induced by BAX trigger site activator 1 in the ARPE-19 retinal pigment epithelial cell model.},
journal = {European journal of pharmacology},
volume = {},
number = {},
pages = {178975},
doi = {10.1016/j.ejphar.2026.178975},
pmid = {42134759},
issn = {1879-0712},
abstract = {Mitochondrial dysfunction in the retinal pigment epithelium (RPE) is a key pathological feature of age-related macular degeneration (AMD). However, mechanistically defined experimental models that recapitulate stress-mediated mitochondrial injury remain limited. Bcl-2-associated X (BAX), a key pro-apoptotic effector, serves as a critical upstream regulator of mitochondrial outer membrane permeabilization. In this study, we systematically characterized mitochondrial dysfunction induced by BAX trigger site activator 1 (BTSA1), a selective small-molecule BAX activator, in ARPE-19 cells. Treatment with BTSA1 (3-60 μM) for 24 and 48 h induced a concentration- and time-dependent reduction in cell viability, accompanied by caspase-3 activation. Mitochondrial membrane potential, assessed via tetramethylrhodamine ethyl ester staining, was markedly reduced in a BAX-dependent manner and associated with increased reactive oxygen species production following prolonged exposure or at high concentrations. BTSA1 profoundly altered mitochondrial dynamics by promoting DRP1-mediated fission while suppressing fusion through MFN2 downregulation and stress-associated OPA1 processing, resulting in pronounced mitochondrial fragmentation. Furthermore, BAX activation elicited a biphasic response in mitochondrial quality control pathways: mild stress induced impaired autophagic flux and compensatory mitochondrial biogenesis, whereas severe stress triggered mitophagy accompanied by failure of biogenic compensation. These coordinated alterations closely mirror mitochondrial pathologies observed in the degenerating RPE in AMD. Collectively, our findings demonstrate that BAX activation by BTSA1 is sufficient to induce a comprehensive cascade of mitochondrial dysfunction. This system represents a mechanistically defined experimental model for dissecting BAX-mediated mitochondrial pathology and evaluating therapeutic strategies to preserve mitochondrial integrity in AMD.},
}

@article {pmid42115584,
year = {2026},
author = {Alshahrouri, B and Blass, BE and Dürig, T and Fassihi, R},
title = {Applications of Thermoresponsive Hydrogels for Sustained Drug Release in Ocular and Intravitreal Formulations Treating Visual Impairments.},
journal = {The AAPS journal},
volume = {28},
number = {3},
pages = {},
pmid = {42115584},
issn = {1550-7416},
mesh = {*Hydrogels/chemistry/administration & dosage ; Humans ; Delayed-Action Preparations/administration & dosage ; Temperature ; *Drug Delivery Systems/methods ; Intravitreal Injections ; Drug Liberation ; Animals ; *Vision Disorders/drug therapy ; Ophthalmic Solutions/administration & dosage ; *Eye Diseases/drug therapy ; Administration, Ophthalmic ; },
abstract = {Vision loss is one of the most debilitating eye impairments, with the leading causes such as cataracts, glaucoma, injuries to the surface of the eye and age-related macular degeneration, significantly affecting a person's quality of life and placing a substantial burden on healthcare systems. Effective treatment of these conditions remains challenging due to the complex anatomical and physiological barriers of the eye, which limit the penetration and retention of topically and intravitreally administered drugs. As a result, conventional ocular therapies often exhibit poor therapeutic efficacy, low bioavailability, necessitating frequent administration, reducing patient compliance, and increasing the risk of treatment-related complications. Thermoresponsive hydrogels have emerged as a promising class of in situ-forming drug delivery systems that utilize physiological temperature as a trigger to transition from a sol to a gel state upon administration. This sol-gel transition enhances precorneal or intraocular residence time, improves mucoadhesion, and facilitates sustained drug release. These characteristics make thermoresponsive hydrogels particularly suitable for ocular and intravitreal formulations targeting both anterior and posterior-segment diseases. Thermoresponsive polymers may exhibit lower critical solution temperature (LCST), upper critical solution temperature (UCST), or combined LCST-UCST phase behavior depending on polymer composition, enabling tunable gelation properties to control rate of drug release profiles. This review provides an overview of recent developments in thermoresponsive hydrogels for ophthalmic drug delivery, including emerging dual-responsive systems, with emphasis on gelation mechanisms, drug-release kinetics, and therapeutic applications in anterior and posterior-segment diseases. Key translational considerations, including formulation stability, sterilization, scalability, and regulatory challenges, are also discussed. In addition, the article highlights future research directions to support the continued application and clinical translation of thermoresponsive hydrogel-based ocular drug delivery systems.},
}

*Hydrogels/chemistry/administration & dosage
Humans
Delayed-Action Preparations/administration & dosage
Temperature
*Drug Delivery Systems/methods
Intravitreal Injections
Drug Liberation
Animals
*Vision Disorders/drug therapy
Ophthalmic Solutions/administration & dosage
*Eye Diseases/drug therapy
Administration, Ophthalmic

@article {pmid42116404,
year = {2026},
author = {Han, Y and Feng, J and Gong, X and Tang, G and Yin, Y and Li, J and Liu, Y and Zhang, J and Song, J and Bi, H},
title = {Mitophagy in ophthalmic pathologies: Molecular mechanisms and therapeutic implications.},
journal = {Medicine},
volume = {105},
number = {19},
pages = {e47600},
pmid = {42116404},
issn = {1536-5964},
support = {2021LCZX09//the Focus on Research and Development Plan in Shandong Province/ ; ZR2021LZY045//the Natural Science Foundation of Shandong Province/ ; 202307021729//the Shandong Province Medical and Health Science and Technology Project/ ; No. Q-2023015//Traditional Chinese Medicine Science and Technology Project of Shandong Province/ ; },
mesh = {Humans ; *Mitophagy/physiology ; Macular Degeneration/physiopathology ; *Eye Diseases/physiopathology ; Diabetic Retinopathy/physiopathology ; Mitochondria/metabolism ; Glaucoma/physiopathology ; },
abstract = {Mitophagy, a selective autophagic process responsible for the degradation of dysfunctional mitochondria, serves as a critical regulator of cellular homeostasis. Despite its emerging significance in ocular pathophysiology, comprehensive analyses bridging molecular mechanisms to clinical translation remain scarce. The retina, with its high metabolic demands and reliance on mitochondrial bioenergetics, is particularly vulnerable to mitophagic dysregulation, which has been mechanistically linked to the pathogenesis of major ophthalmic disorders. This review systematically elucidates the molecular architecture of mitophagy, focusing on its dual roles in disease progression and cytoprotection across glaucoma, age-related macular degeneration (AMD), and diabetic retinopathy (DR). By integrating mechanistic insights with therapeutic implications, we not only delineate conserved regulatory pathways (e.g., PINK1 [PTEN-induced kinase 1]/Parkin, BNIP3 [BCL2/adenovirus E1B 19 kDa interacting protein 3], FUNDC1 [FUN14 domain containing 1]) but also propose a roadmap for targeting mitophagic checkpoints through precision pharmacology and combinatorial regimens. Our synthesis underscores the urgency of translating mitophagy modulation into clinical strategies to address unmet needs in retinal degenerative diseases.},
}

Humans
*Mitophagy/physiology
Macular Degeneration/physiopathology
*Eye Diseases/physiopathology
Diabetic Retinopathy/physiopathology
Mitochondria/metabolism
Glaucoma/physiopathology

@article {pmid42122923,
year = {2026},
author = {Rinaldi, M and Cennamo, G and Passaro, ML and Chiosi, F and Falco, F and D'Alessandro, A and Strianese, D and Costagliola, C},
title = {Targeting Macular Pigment in Intermediate Age-Related Macular Degeneration: Oral Supplementation Versus Transscleral Iontophoresis in a Prospective Pilot Study.},
journal = {Journal of clinical medicine},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/jcm15093188},
pmid = {42122923},
issn = {2077-0383},
abstract = {Background/Objectives: Macular pigment optical density (MPOD) represents a biomarker of retinal antioxidant status in intermediate age-related macular degeneration (iAMD). Strategies aimed at increasing macular carotenoid availability may contribute to disease stabilization. This study evaluated the effects of oral supplementation and transscleral iontophoresis on MPOD and retinal parameters in iAMD. Methods: This prospective, non-randomized pilot study included 60 eyes of 60 patients with intermediate AMD enrolled at the Eye Clinic of the University of Naples Federico II between July 2024 and May 2025 (ClinicalTrials.gov NCT06465342). Patients received either oral carotenoid supplementation (n = 30) or transscleral iontophoresis (n = 30). Best-corrected visual acuity (BCVA), central macular thickness (CMT), and MPOD measured by one-wavelength reflectometry (Visucam 200; Carl Zeiss Meditec, Jena, Germany) were assessed at baseline and 6 months. Results: BCVA remained stable in both groups without significant changes (p > 0.05). MPOD significantly increased in the iontophoresis group (0.40 ± 0.11 to 0.49 ± 0.12, p < 0.001) with no statistically significant difference between them (p = 0.09). CMT showed a mild, non-significant increase in both groups (p > 0.05). No adverse events were observed. Conclusions: Both oral supplementation and transscleral iontophoresis were associated with a significant increase in MPOD while preserving visual acuity in intermediate AMD. Within the limitations of this non-randomized pilot study, transscleral iontophoresis produced MPOD changes comparable to those observed with oral supplementation. These findings are exploratory and support further investigation of localized delivery strategies in larger, randomized trials.},
}

@article {pmid42122986,
year = {2026},
author = {Shakaki, N and Yu, M},
title = {Targeting Neuroinflammation and Oxidative Stress to Slow Neurodegeneration in the Visual System.},
journal = {Journal of clinical medicine},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/jcm15093254},
pmid = {42122986},
issn = {2077-0383},
support = {P30-EY025585/EY/NEI NIH HHS/United States ; },
abstract = {PURPOSE: Neuroinflammation and oxidative stress are increasingly recognized as central, interconnected drivers of neurodegeneration in the visual system. This review examines the pathogenic mechanisms shared across glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR), and Alzheimer's disease (AD), and evaluates the therapeutic rationale for targeting both pathways simultaneously.

METHODS: A narrative review of peer-reviewed literature was conducted using PubMed. Searches combined the following MeSH terms: neuroinflammation, oxidative stress, retinal neurodegeneration, microglia, Müller glia, mitochondrial dysfunction, glaucoma, age-related macular degeneration, diabetic retinopathy, and Alzheimer's disease. Priority was given to original research, systematic reviews, and high-impact publications from 2000 through 2025. However, seminal foundational works were included regardless of publication date. Studies were selected based on relevance to glial activation, mitochondrial dysfunction, reactive oxygen and nitrogen species, and disease-specific neuronal outcomes.

RESULTS: Across all four diseases, persistent microglial and Müller glial activation, mitochondrial electron transport chain dysfunction, and excess reactive oxygen species (ROS) and reactive nitrogen species (RNS) production form a self-amplifying feed-forward loop that accelerates neuronal injury. In glaucoma, these mechanisms drive intraocular pressure-independent retinal ganglion cell loss. In AMD and DR, lipid dysregulation, complement activation, and chronic hyperglycemia sustain oxidative-inflammatory injury to the retinal pigment epithelium, photoreceptors, and neurovasculature. In AD, retinal amyloid deposition and oxidative stress mirror cortical pathology, positioning the retina as a noninvasive biomarker site.

CONCLUSIONS: Neuroinflammation and oxidative stress constitute unifying upstream mechanisms across major vision-threatening neurodegenerative diseases. Combination therapeutic strategies that simultaneously modulate glial activation and restore redox homeostasis may offer superior neuroprotective efficacy compared to approaches targeting isolated downstream mediators.},
}

@article {pmid42123125,
year = {2026},
author = {Schrittwieser, J and Kuchernig, L and Mares, V and Steiner, I and Birner, K and Frommlet, F and Borrelli, E and Bogunović, H and Sacu, S and Reiter, GS},
title = {Choriocapillaris Flow-Enriched Prediction of Retinal Sensitivity Using OCT-Derived Biomarkers in Intermediate Age-Related Macular Degeneration.},
journal = {Journal of clinical medicine},
volume = {15},
number = {9},
pages = {},
doi = {10.3390/jcm15093392},
pmid = {42123125},
issn = {2077-0383},
abstract = {Objectives: To assess the association of structural biomarkers derived from optical coherence tomography (OCT) and choriocapillaris (CC) flow information with point-wise retinal sensitivity (PWS) measured by microperimetry (MP) in intermediate age-related macular degeneration (iAMD). Methods: Patients with iAMD received imaging with spectral-domain (SD)-OCT (Spectralis, Heidelberg Engineering) and OCT-angiography (OCT-A) (PLEX Elite 9000, ZEISS). In addition, MP examinations in photopic setting (MP-3, NIDEK) and mesopic background illumination (MAIA2, ICare) were performed. The thickness of the ellipsoid-zone (EZ) and the outer nuclear layer (ONL), as well as the volume of drusen and HRF, were segmented using deep-learning (DL)-based approaches. CC flow deficit percentage (FD%) was extracted from OCT-A slabs using a novel binarization method. Semiautomatic co-registration of MP examinations, OCT-A slabs, and OCT volumes was performed. Three exploratory models were calculated using multivariable mixed-effects models: (1) structure-function (SF) using structural OCT biomarkers, (2) flow-function (FF) utilizing OCT-A derived flow information, and (3) structure-flow-function (SFF) incorporating both OCT and OCT-A data. Model performance was evaluated using AIC and BIC criterion. Results: 19 eyes of 19 patients were evaluated, totalling 3297 MP-stimuli, 1873 B-scans, and 19 OCT-A slabs. Mean (SD) age was 76 (7) years, and sensitivity was 26.0 (3.36) dB in the MP-3 and 22.42 (3.64) dB in the MAIA2. Mesopic MAIA2 examinations showed significantly lower PWS values (-3.56 to -3.63 dB; p < 0.001). Drusen and HRF volume decreased PWS (-0.6 [95% CI: -1.04; -0.16] dB/nL; p = 0.007 and -9.56 [95% CI: -12.86; -6.26] dB/nL; p < 0.001), while ONL was positively associated with PWS (0.06 [0.05; 0.07] at an eccentricity of 5.2°; p < 0.001) in the SF model. CC FD% was not significantly associated with PWS in the FF and the SFF model (p > 0.05 in both cases). In the SFF model drusen volume (-1.69 [95% CI: -2.09; -1.29] dB/nL; p < 0.001), EZ (0.04 [95% CI: 0.02; 0.06] dB/µm; p < 0.001), and ONL thickness (0.03 [95% CI: 0.02; 0.04] dB/µm; p < 0.001) were significant predictors for PWS. The SF model exhibited the lowest AIC and BIC indicating best model performance. Conclusions: Structural parameters derived from SD-OCT such as HRF, drusen volume, and outer retinal layer thickness may be more closely associated with PWS, with CC FD% as an OCT-A-derived metric contributing limited additional explanatory benefit in cross-sectional analyses.},
}

@article {pmid42123608,
year = {2026},
author = {Alibrandi, S and Donato, L},
title = {Special Issue "Retinal Diseases and Macular Degeneration: Cell Biology and Molecular Genetics".},
journal = {International journal of molecular sciences},
volume = {27},
number = {9},
pages = {},
doi = {10.3390/ijms27094022},
pmid = {42123608},
issn = {1422-0067},
mesh = {Humans ; *Macular Degeneration/genetics/pathology/metabolism ; *Retinal Diseases/genetics/metabolism/pathology ; Animals ; },
abstract = {Retinal diseases and macular degeneration continue to represent major global health challenges, having profound personal, social, and economic implications [...].},
}

Humans
*Macular Degeneration/genetics/pathology/metabolism
*Retinal Diseases/genetics/metabolism/pathology
Animals

@article {pmid42124582,
year = {2026},
author = {Nandakumar, S and Farjood, F and Bertucci, T and Lotz, S and Sai, S and Wang, Y and Kozak, JA and Arduini, BL and Stern, JH and Boles, NC and Temple, S},
title = {Single Cell Transcriptomics and Surface Protein Expression Reveal Distinct Cellular and Molecular Phenotypes in Human RPESC-RPE and PSC-RPE.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.02.26.708319},
pmid = {42124582},
issn = {2692-8205},
abstract = {Current retinal pigment epithelium (RPE) cell replacement strategies in trials for age-related macular degeneration (AMD) are based on either pluripotent stem cell (PSC) or adult RPE stem cell (RPESC) sources. We used Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq) to simultaneously assess single-cell transcriptomic and surface protein information, comparing these two RPE sources. Both RPESC-RPE and PSC-RPE expressed key RPE markers and exhibited cellular heterogeneity. However, RPESC-RPE had higher expression of genes related to mature retinal functions, whereas PSC-RPE had greater expression of genes involved in stem cell development and differentiation. We identified two surface proteins that distinguished the cell types. The "don't eat me" signal, CD24, was detected robustly on adult RPESC-RPE cells, while CD57 was detected on most PSC-RPE cells. The differences in gene and surface protein expression suggest that the two RPE sources differ in functional, adhesion, and immunomodulatory properties, which may impact transplantation outcomes.},
}

@article {pmid42125429,
year = {2026},
author = {Hiltunen, TO and Kaarniranta, K and Kivinen, N},
title = {Real World Data About the Treatment of Wet Age-Related Macular Degeneration in Kuopio University Hospital During 2019-2021 Using a PRN Regimen.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {595553},
pmid = {42125429},
issn = {1177-5467},
abstract = {PURPOSE: To evaluate the real-world effectiveness of a pro re nata (PRN) anti-vascular endothelial growth factor (anti-VEGF) regimen for neovascular age-related macular degeneration (nAMD) during 2019-2021 at Kuopio University Hospital, including the COVID-19 pandemic period.

METHODS: This retrospective study included 107 patients (162 eyes) treated with intravitreal anti-VEGF injections for nAMD. The included eyes were not treatment-naive at study entry but had received anti-VEGF treatment before 2019. Annual injection numbers, drug choice (bevacizumab or aflibercept 2 mg), central retinal thickness (CRT), and visual acuity (VA) were analyzed from diagnosis through 2021 using independent-sample t-tests.

RESULTS: The mean number of injections in the first treatment year was 6.79 ± 2.32. During 2019-2021, annual means were 5.09 ± 2.33, 5.40 ± 2.10, and 4.96 ± 2.11, respectively. Bevacizumab-treated eyes received significantly more injections than aflibercept-treated eyes across all years (p < 0.01 for 2019; p < 0.05 for 2020-2021). Mean VA declined from 70 ± 57 ETDRS letters at diagnosis to 62 ± 57 ETDRS letters by late 2021 (p < 0.0001). In the aflibercept-only subgroup, the decline was smaller and not significant (68 ETDRS letters ± 55 ETDRS letters to 66 ± 56 ETDRS letters; p > 0.27). CRT decreased significantly from 388.4 ± 139.4 µm at diagnosis to 320.8 ± 114.7 µm in 2019 and remained stable thereafter (p < 0.0001 vs. baseline; p > 0.5 between years).

CONCLUSION: The PRN regimen maintained anatomical outcomes but resulted in gradual visual decline, likely due to fewer injections, particularly during the COVID-19 period. Aflibercept required fewer injections without compromising outcomes. Transitioning toward a treat-and-extend protocol may enhance visual stability and cost-effectiveness in nAMD care.},
}

@article {pmid42125505,
year = {2026},
author = {Awan, B and Elsaigh, M and Hesham Gamal, M and Elbahnasawy, SE and Badee, M},
title = {Performance of Artificial Intelligence Systems for Automated Segmentation and Quantification of Retinal Fluid and Pathology in Optical Coherence Tomography Scans: A Systematic Review and Meta-Analysis.},
journal = {Cureus},
volume = {18},
number = {5},
pages = {e108662},
pmid = {42125505},
issn = {2168-8184},
abstract = {Optical coherence tomography (OCT) plays a crucial role in diagnosing retinal diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), as well as in identifying neurodegenerative biomarkers. Despite advancements in U-Net-based convolutional networks for OCT image segmentation, there is a lack of systematic reviews comparing their performance with expert manual segmentations. This review aims to assess the efficacy of these automated networks in segmenting retinal fluid and pathology in OCT images. By searching three different databases, PubMed, Web of Science, and Scopus, over the past five years, we conducted this systematic review and meta-analysis using data from 16 diagnostic-accuracy studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. The analysis used mean and standard deviation for the continuous outcomes and employed a random-effects model. Analyses were performed using Review Manager software version 5.4 (The Cochrane Collaboration, London, UK, 2020). Artificial intelligence (AI) and human Dice scores did not differ significantly (standardized mean difference (SMD) = -0.08; 95% CI: -1.16 to 0.99; p = 0.88), nor did intraclass correlation coefficient (ICC) values (SMD = -0.13; 95% CI: -5.70 to 5.45; p = 0.96). However, very high heterogeneity (I[2] > 90%) limits the reliability of these pooled estimates. AI achieved expert-level Dice scores for subretinal fluid (0.88-0.96) and geographic atrophy (0.94). Intraretinal fluid was more challenging (Dice 0.79-0.89). Volumetric reliability was strong (ICCs > 0.94). Device-dependent variability was substantial; kappa was 0.37 for ZEISS versus 0.73 for Spectralis, indicating a need for device-specific optimization. Volumetric analyses revealed minor systematic overestimation (mean difference: -0.05 mm[2]). Processing times ranged from 100 milliseconds per B-scan to several seconds per volume, representing substantial time savings versus manual segmentation. Fully automated U-Net pipelines reach expert-level accuracy for subretinal fluid and geographic atrophy but remain limited for intraretinal fluid and show marked device-dependent variability. Clinical translation requires four priorities: standardized multi-device benchmarks, domain adaptation for cross-platform robustness, hybrid AI-human workflows pairing automated pre-segmentation with expert oversight, and prospective clinical trials. These steps are needed to move AI segmentation from a research tool to a clinical decision-support system.},
}

@article {pmid42125560,
year = {2026},
author = {Robinson, K and Lester, K and Persaud, S and Depry, C and Cooper, S},
title = {Continuing Medical Education as a Tool to Accelerate the Adoption of Extended-Duration Intravitreal Anti-VEGFs.},
journal = {Journal of CME},
volume = {15},
number = {1},
pages = {2669419},
pmid = {42125560},
issn = {2833-8073},
abstract = {PURPOSE: This study evaluated the impact of a comprehensive, curriculum-based continuing education (CE) programme on the adoption of second-generation intravitreal anti-VEGF therapies among ophthalmologists treating patients with diabetic macular oedema (DME) or neovascular age-related macular degeneration (nAMD).

METHODS: A multimodal educational curriculum was developed for eye care providers, incorporating principles of adult learning and marketing strategies. The curriculum included 14 CE activities (didactic content, case scenarios, live meetings, interprofessional activities, and downloadable resources) delivered from July 2024 through April 2026. Surveys, assessing knowledge, attitudes, and clinical decision-making, were administered before, during, and after participation. Participants were categorised as single-activity learners (one activity) or multiple-activity learners (three or more activities). Statistical analyses compared knowledge acquisition, comfort, and adoption of second-generation anti-VEGF agents between groups.

RESULTS: As of September 2025, 5,975 providers completed at least one activity; 398 providers, with complete data, were analysed (289 single-activity, 109 multiple-activity learners). Both groups, post education, demonstrated improved knowledge and comfort with second-generation anti-VEGF agents. Multiple-activity learners had higher baseline knowledge and consistently selected second-generation agents more frequently in case scenarios. Single-activity learners showed greater knowledge gains, while multiple-activity learners maintained higher overall knowledge. The curriculum increased preparedness for future use of new therapies, particularly among low-frequency injectors (<9 injections/week), though some barriers to adoption persisted.

CONCLUSION: A curriculum-based, multimodal CE programme can accelerate the adoption of innovative therapies by improving clinician knowledge, comfort, and clinical decision-making. Iterative, data-driven education is effective in bridging gaps between emerging science and real-world practice, ultimately supporting better patient outcomes in nAMD and DME care.},
}

@article {pmid42127969,
year = {2026},
author = {Jensen, N and Ly, K and Kochnev Goldstein, A and Devaud, Q and Palanker, D},
title = {Maximizing the fidelity of a photovoltaic subretinal prosthesis for human patients.},
journal = {Journal of neural engineering},
volume = {},
number = {},
pages = {},
doi = {10.1088/1741-2552/ae6d77},
pmid = {42127969},
issn = {1741-2552},
abstract = {PRIMA subretinal implants provide pros thetic vision to patients blinded by age-related macular degeneration, with acuity closely matching the sampling limit of the pixel pitch: a single 100µm pixel per line of a letter corresponds to 20/420 acuity. Decreasing the pixel size in the same flat geometry is difficult due to the constrained electric field, especially consid ering a 40µm thick debris layer separating the implant from the target neurons. Here we optimize the electrode design to help overcome such limitations. Approach. An end-to-end modeling pipeline combines the retinal photovoltaic implant simulator (RPSim) based on the Xyce circuit simulator with an interface to COMSOL Multiphysics for electric field modelling. It was used to generate and characterize implants in an open-loop sampling based optimization. Implant performance was evaluated with respect to voltage drop across bipolar cells (representing the stimulation strength), pattern contrast, and neural selectivity. Main Results. The highest selectivity in stimulation of bipolar cells was achieved with arrays having active electrodes on pillars and return electrodes connected in a mesh surrounding the photovoltaic pixels in the array. Such a design, even with pixels down to 20µm, provides stimulation strength exceeding, and contrast similar to that of flat 100µm PRIMA pixels. Significance. Using a novel 3-D electrode design, the pitch of the photovoltaic array can be decreased to 20µm, while providing performance that exceeds the flat 100µm PRIMA pixels. In humans, 20µm resolution on the retina corresponds to a visual acuity of 20/80 a five times improvement compared to the current clinical device. .},
}

@article {pmid42114812,
year = {2026},
author = {Sánchez-Vela, L and Brosa, H and Martin-Pinardel, R and Bernal-Morales, C and Parrado-Carrillo, A and Moll-Udina, A and Puzo-Bayod, M and Garay-Aramburu, G and Arruabarrena, C and Sararols-Ramsay, L and Calvo-Perez, P and Zapata, MA and Garrido, M and Abraldes, M and Ruiz-Moreno, JM and Broc-Iturralde, L and Velázquez-Villoria, D and Escobar-Barranco, JJ and Gallego-Pinazo, R and Figueroa, MS and García-Layana, A and Figueras-Roca, M and Gillies, MC and Casaroli-Marano, RP and Zarranz-Ventura, J and , },
title = {Vascular endothelial growth factor inhibitors outcomes in good vision eyes with neovascular age-related macular degeneration. Fight Retinal Blindness SPAIN Report 4.},
journal = {Canadian journal of ophthalmology. Journal canadien d'ophtalmologie},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jcjo.2026.04.001},
pmid = {42114812},
issn = {1715-3360},
abstract = {PURPOSE: To evaluate the visual outcomes in neovascular age-related macular degeneration (nAMD) eyes initiating anti-vascular endothelial growth factor treatment with baseline visual acuity (VA) ≥70 letters.

METHODS: Multicentre, real-world, and national database study. Demographics, VA, number of injections, and patient visit data were collected using a validated online tool. Subgroup analysis included 2 nonoverlapping participant groups defined by baseline VA: Good vision eyes (GVE, "70-100 letters") and non-GVE ("0-69 letters") at 12, 24, and 36 months.

RESULTS: A total of 3 138 eyes (2 520 patients) were included in the analysis, followed up for 12 (n = 2 426; 77.3%), 24 (n = 1 793; 57.1%), and 36 months (n = 1 167; 37.2%). GVE had significantly better 24-month final VA (71.0 ± 13.8 vs 52.3 ± 23.2; p < 0.001) than NGVE. Mean VA change (letters) at 12, 24, and 36 months of follow-up was significantly lower in the GVE -2.4 (-3.1, -1.6), -4.5 (-5.6, -3.5), and -7.8 (-9.4, -6.2) than in NGVE +6.7 (5.8, 7.6), +5.0 (3.8, 6.2), and +4.0 (2.5, 5.5) group, respectively. The number of injections and percentage of visits with active lesions were higher in GVE through 36 months.

CONCLUSIONS: The mean VA of GVE tends to drop, but it is still much higher than NGVE eyes at 12, 24, and 36 months. Early detection and prompt treatment are key and should be considered in treatment access policies, regulatory frameworks, and clinical guidelines, as defining a threshold to start treatment may have a clear impact on final visual function, patient autonomy and legal blindness rates in nAMD patients.},
}

@article {pmid42039665,
year = {2026},
author = {Mohan, VB and Yucel, EI and Fine, I and Boynton, G},
title = {Using Virtual Patients to Predict Perceptual Outcomes for Optogenetic Sight Recovery Technologies.},
journal = {bioRxiv : the preprint server for biology},
volume = {},
number = {},
pages = {},
pmid = {42039665},
issn = {2692-8205},
abstract = {Optogenetics is emerging as a powerful approach for partial vision restoration, with at least three ongoing clinical trials in humans testing novel light-sensitive proteins (opsins) in patients with inherited retinal degenerative disorders. These therapies aim to restore light responsiveness by introducing opsins into surviving retinal cells, such as bipolar or ganglion cells, enabling them to generate neural activity in response to visual stimuli. One ongoing difficulty in selecting promising opsins for clinical development is that there is no way to predict patient perceptual outcomes from optogenetically evoked neural activity as measured ex vivo. Here, we introduce a virtual patient framework that quantitatively links the sensitivity and speed of opsin-mediated retinal responses to predicted patient outcomes, and show how this framework can predict temporal contrast sensitivity functions - a well-established measure of perceptual performance - from microbial opsin photocurrent responses. Our simulations demonstrate that opsin sensitivity and kinetics jointly determine perceptual outcomes, and that enhancing sensitivity at the expense of temporal resolution can degrade the perception of fast-moving stimuli. This computational platform provides a generalizable tool for comparing and selecting the most effective opsins for clinical translation, thereby guiding the design and optimization of next-generation sight restoration strategies.},
}

@article {pmid42107714,
year = {2026},
author = {Grzybowski, A and Liu, TYA and Popovic, MM and Zhao, A and Miyake, M and Takahashi, H and Kawasaki, R and He, M and Gong, X and Goktas, P and Jin, K},
title = {Global approval and certification of ophthalmic AI devices: A comparative regulatory perspective.},
journal = {Asia-Pacific journal of ophthalmology (Philadelphia, Pa.)},
volume = {},
number = {},
pages = {100328},
doi = {10.1016/j.apjo.2026.100328},
pmid = {42107714},
issn = {2162-0989},
abstract = {Artificial intelligence (AI) tools are rapidly reshaping ophthalmology by improving screening and diagnosis for diabetic retinopathy, age-related macular degeneration, glaucoma, and increasingly retina-based systemic risk assessment. This narrative review provides a comparative assessment of regulatory pathways governing ophthalmic AI and software as a medical device (SaMD) across the United States, European Union, United Kingdom, Australia, China, Japan, Canada, India, and selected emerging jurisdictions. We used a structured search of public regulator databases, guidance documents, manufacturer disclosures, and peer-reviewed literature to assemble a representative sample of marketed or authorized devices through August 2025; the device inventory is illustrative rather than exhaustive. Key differences persist in device classification, evidence expectations, change management for adaptive algorithms, and post-market oversight. Examples such as LumineticsCore, EyeArt, DrNoon for CVD, CLAiR, and EyeWisdom illustrate how risk-based approaches vary across jurisdictions. These inconsistencies can delay multi-region deployment and complicate implementation, supporting the need for lifecycle-focused and internationally aligned standards for safe, transparent, and equitable use of ophthalmic AI.},
}

@article {pmid42107776,
year = {2026},
author = {Novarese, C and Vyas, C and Berni, A and Bacherini, D and Chaudhary, V and Dolz-Marco, R and Gallego-Pinazo, R and Mastropasqua, R and Reiter, GS and Subhi, Y and Bandello, F and Reibaldi, M and Borrelli, E},
title = {- Systematic Review - Macular Neovascularization in Neovascular AMD: A Systematic Review of OCTA-Based Assessments and Challenges in Standardization.},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.05.002},
pmid = {42107776},
issn = {2468-6530},
abstract = {TOPIC: This systematic review evaluates the methodologies employed for assessing the macular neovascularization (MNV) in neovascular age-related macular degeneration (AMD) using optical coherence tomography angiography (OCTA). It focuses on identifying methodological heterogeneity in imaging and analysis protocols and its implications for clinical and research applications.

CLINICAL RELEVANCE: Accurate assessment of MNV is critical for understanding disease activity, monitoring treatment response, and guiding clinical management in AMD. OCTA offers non-invasive, high-resolution visualization of neovascular networks, but variability in device types, scan protocols, segmentation strategies, and post-processing methods hampers reproducibility and comparability across studies.

METHODS: A systematic literature search was conducted in PubMed (Medline) and the Cochrane Library from inception through April 3, 2025. The review protocol was prospectively registered in PROSPERO (CRD420251046977). Studies included patients with neovascular AMD who underwent OCTA for MNV evaluation, irrespective of device type or scan parameters. Data extraction focused on OCTA technology, scan sizes, segmentation strategies, image processing techniques, quantitative metrics, and approaches to artifact reduction. A descriptive synthesis was performed.

RESULTS: A total of 155 studies, comprising 9,025 patients (9,669 eyes), were included. MNV subtypes included type 1 (5,059 eyes), type 2 (973 eyes), type 3 (321 eyes), and mixed lesions (138 eyes); 12 studies did not specify subtype. OCTA devices included spectral-domain (86 studies) and swept-source systems (64 studies), with PLEX Elite 9000 and RTVue XR Avanti most frequently used. Scan sizes varied, predominantly 3×3 mm and 6×6 mm. Segmentation strategies and slab boundaries exhibited marked heterogeneity, with frequent manual corrections required for accurate visualization. Quantitative analyses employed diverse thresholding and binarization techniques, and only a minority of studies addressed projection artifact correction, highlighting substantial variability in methodological approaches across studies.

CONCLUSION: OCTA provides detailed, non-invasive assessment of MNV in AMD, but methodological heterogeneity-including variability in devices, scan protocols, segmentation, binarization, and artifact management-limits comparability across studies. Standardized imaging and analytical protocols are urgently needed to improve reproducibility, enable reliable biomarker development, and enhance clinical utility in AMD management.},
}

@article {pmid42109964,
year = {2026},
author = {Danish, E and Alsulami, R and Baeshen, H},
title = {CDH3 Mutation in Saudi Arabia: A Case of Hypotrichosis With Juvenile Macular Dystrophy.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e106554},
pmid = {42109964},
issn = {2168-8184},
abstract = {Congenital sparse scalp hair and progressive vision loss are hallmarks of hypotrichosis with juvenile macular dystrophy (HJMD), a rare autosomal recessive condition. We present a rare case of HJMD from Saudi Arabia. A six-year-old Saudi girl, born to first-cousin consanguineous parents, presented with sparse scalp hair growth from birth and decreased night vision from one year of age. Full-field electroretinography (ffERG) suggested cone-rod dysfunction. Fundus photographs showed pigmentary degenerative changes around the macular area and mid-periphery. HJMD was suspected. A homozygous missense mutation, c.1918T>G (p.Cys640Gly), was discovered in exon 4 (NM_001793.5) of the CDH3 gene by whole-exome sequencing. Patients with these clinical characteristics should be evaluated for HJMD, a rare genetic cause of hypotrichosis and macular degeneration. Although several mutations have been reported in Saudi Arabia, the CDH3 c.1918T>G variant identified in this patient further expands the understanding of the genetic spectrum of HJMD in the region.},
}

@article {pmid42110464,
year = {2026},
author = {Li, Y and Fu, X and Huang, L and Xiao, L and Chen, D},
title = {Global research trends and hotspots in the pathophysiology, imaging and therapy of type 3 macular neovascularization (MNV3) in age-related macular degeneration (AMD).},
journal = {Frontiers in medicine},
volume = {13},
number = {},
pages = {1811978},
pmid = {42110464},
issn = {2296-858X},
abstract = {BACKGROUND: To provide an overview of the research hotspots and directions of type 3 macular neovascularization (MNV3) in age-related macular degeneration by bibliometric analysis.

METHODS: Publications related to MNV3 were retrieved from two databases, the Science Citation Index-Expanded database of the Web of Science Core Collection (WoSCC) and PubMed. CiteSpace was utilized to analyze country distribution, keyword bursts, and co-cited references. VOSviewer was employed to identify collaborative authors and the keyword co-occurrence network.

RESULTS: A total of 564 publications were identified from 2001 to 2026. They were performed in 97 countries, with the United States leading the way. Kim JW is the most prolific author, while Yannuzzi LA is the most cited author. Investigative Ophthalmology & Visual Science has published the most papers. Retina-The Journal of Retinal and Vitreous Diseases is the most cited journal. In the keyword co-occurrence network, apart from terms related to MNV3, "ranibizumab," "photodynamic therapy" and "optical coherence tomography" are high-frequency keywords, while terms such as "artificial intelligence," "biomarker," and "microglia" have emerged as more recent research hotspots. Research topics can be categorized into four major clusters: pathogenesis, imaging, therapy, clinical prognosis and long-term management. Meanwhile, highly cited co-cited articles successively addressed risk stratification, early identification, imaging evaluation, and standardized therapeutic regimens of MNV3, providing important references for clinical practice.

CONCLUSION: This bibliometric analysis elucidates research hotspots and directions in MNV3 across pathophysiology, imaging, and therapy, and outlines the dynamic development of research in this field.},
}

@article {pmid42111215,
year = {2026},
author = {Hou, J and Ikeda, SI and Yang, Y and Fukuchi, T and Ikeda, C and Imanishi, S and Ma, Z and Chen, J and Mori, K and Torii, H and Fujii, H and Negishi, K and Tsubota, K and Kurihara, T},
title = {The choroidal macrophage polarization significantly influences myopia development in murine models.},
journal = {iScience},
volume = {29},
number = {5},
pages = {115764},
pmid = {42111215},
issn = {2589-0042},
abstract = {While choroidal macrophages regulate homeostasis in macular degeneration, their role in myopia is unclear. In this study, depleting choroidal macrophages via clodronate liposome injections induced myopia. To further dissect their function, introducing polarized classically activated (M1) or alternatively activated (M2) macrophages into a myopia model revealed that both the presence and polarization of choroidal macrophages affect myopia progression. Further exploration in normal mice showed that choroidal M1 macrophages polarization triggered choroidal thinning and promoted myopia progression, whereas M2 macrophages polarization enhanced choroidal thickening and suppressed myopia development. These opposite effects of M1 and M2 macrophages on choroidal thickness and myopia progression appeared to be related to their differential regulation of inflammatory responses and oxidative stress. Taken together, these results support a role for choroidal macrophages and their polarization states in myopia onset and progression, suggesting potential therapeutic strategies for controlling the development and progression of myopia.},
}

@article {pmid42112359,
year = {2026},
author = {Skerka, C and Cochlovius, B and Hüllebrand, JP and Goel, D and Sood, P and Pal, N and Chakravarti, A and Muth, DR and Zeitz, O and Zipfel, PF},
title = {A new perspective on AMD pathogenesis: a sequential Factor H-centered view of complement dysregulation.},
journal = {Frontiers in immunology},
volume = {17},
number = {},
pages = {1814415},
pmid = {42112359},
issn = {1664-3224},
mesh = {Humans ; *Macular Degeneration/immunology/etiology/metabolism/pathology ; *Complement Factor H/metabolism/immunology/genetics ; Animals ; Complement Activation ; Complement C3b Inactivator Proteins ; Complement System Proteins ; Genome-Wide Association Study ; },
abstract = {Age-related macular degeneration (AMD) is a chronic, progressive, retinal disease that primarily affects older individuals and is one of the leading causes of blindness worldwide. Both genetic predisposition and environmental factors contribute to its development. Landmark genome-wide association studies (GWAS) positioned the complement system at the center of AMD research, opening new avenues for understanding disease mechanisms and developing targeted therapies. Among the key complement regulators, Factor H and its splice variant FHL-1, are best known for their roles in inhibiting the alternative pathway. Recent research has expanded our understanding of Factor H, revealing a range of non-canonical functions beyond complement regulation which might also affect AMD pathology. These new functions include roles in cell signaling, tissue protection, metabolism, homeostasis, and modulation of inflammation. In contrast, the related protein FHR1 which is also associated with AMD, exhibits pro-inflammatory properties, promoting monocyte recruitment and activation to facilitate clearance processes. In this review, we summarize the canonical and non-canonical functions of Factor H, FHL-1, and FHR1, and we show how the coordinated action of these three proteins integrates into the broader scope of AMD pathogenesis, including complement activation, inflammation, and photoreceptor degeneration. We also describe the current status of approved complement inhibitors in AMD and emerging therapeutic targets within the complement cascade.},
}

Humans
*Macular Degeneration/immunology/etiology/metabolism/pathology
*Complement Factor H/metabolism/immunology/genetics
Animals
Complement Activation
Complement C3b Inactivator Proteins
Complement System Proteins
Genome-Wide Association Study

@article {pmid42112650,
year = {2026},
author = {Serrano Martinez, P and Cammeraat, M and Teppema, A and van Noorden, CJF and Schlingemann, RO and Klaassen, I},
title = {Human iPSC-Derived Blood Vessel Organoids for Studying Chronic Hypoxia-Induced Microvascular Dysfunction.},
journal = {The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society},
volume = {},
number = {},
pages = {221554261437861},
doi = {10.1369/00221554261437861},
pmid = {42112650},
issn = {1551-5044},
abstract = {Microvascular dysfunction due to hypoxia is a key contributor in the pathogenesis of many disorders including cancer and retinal and cardiovascular diseases, but relevant human models are missing. Here, we present a robust 3D in vitro method with the use of human induced pluripotent stem cell-derived blood vessel organoids to analyze in vitro microvascular remodeling. We present a detailed practical pipeline combining optical tissue clearing, high-resolution immunofluorescence, and surface marker analysis to quantitatively assess hypoxia-driven changes in endothelial cells, pericytes, and the basal lamina. Exposure of these blood vessel organoids to chronic hypoxia (1% O2) for 1 week recapitulated key pathological features, including structural remodeling and a dysregulated secretome with altered vascular endothelial growth factor signaling. This approach establishes a versatile and human-relevant platform to study microvascular remodeling induced by chronic hypoxia and other pathological stimuli and their contribution to microvascular-related diseases.},
}

@article {pmid42113424,
year = {2026},
author = {Elham, A and Liu, H and Li, W and Zhao, J and Yang, X and Zeng, C and Meng, X},
title = {Real-World Persistence with Anti-VEGF Therapy in Neovascular Age-related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42113424},
issn = {2193-8245},
abstract = {INTRODUCTION: The purpose of this study was to quantify real-world non-persistence and non-adherence to intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy among Chinese patients with neovascular age-related macular degeneration (nAMD) and to identify factors associated with treatment continuity in routine practice.

METHODS: This single-center retrospective cohort study was conducted at a one-stop intravitreal injection (IVI) clinic (Dalian University Affiliated Zhongshan Hospital) and included consecutive patients initiating anti-VEGF therapy between 1 August 2022 and 1 August 2024 (N = 179). Non-persistence was defined as no visit or treatment for ≥ 6 months. Among patients remaining on therapy, non-adherence was defined as ≥ 2 visit or injection gaps > 16 weeks within any 12-month window. Cox proportional-hazards models were used for time-to-event analyses.

RESULTS: The median age was 78 years (IQR 71-86 years), and 26% of patients received bilateral injections. Over a median follow-up of 383 days, 117 of 179 patients (65.4%) became non-persistent. Completion of the initial loading phase was associated with a lower hazard of discontinuation (adjusted HR 0.61, 95% CI 0.38-0.98), with similar estimates in prespecified sensitivity analyses. Among patients remaining on therapy (n = 62), 32.3% met criteria for non-adherence. In parsimonious models, increasing age was associated with a higher likelihood of extended treatment gaps, although this secondary finding was exploratory.

CONCLUSION: In this pro re nata (PRN)-managed cohort, loss to follow-up was frequent, and one-third of persistent patients experienced clinically meaningful schedule deviations. Early treatment regularity-particularly completion of the loading phase-was the most actionable factor associated with improved persistence. Associations between older age and non-adherence highlight the need to address age-related barriers to sustained care, but should be interpreted cautiously given the exploratory nature of this secondary endpoint. Strategies focusing on early phase support and burden reduction may help narrow the real-world efficacy gap in nAMD management.},
}

@article {pmid42114678,
year = {2026},
author = {Borrelli, E and Bandello, F and Bhutto, IA and Reibaldi, M and Edwards, MM},
title = {Tracing the Journey from Histology to Imaging: Exploring the Retina and Choroid in Age-related Macular Degeneration.},
journal = {Progress in retinal and eye research},
volume = {},
number = {},
pages = {101475},
doi = {10.1016/j.preteyeres.2026.101475},
pmid = {42114678},
issn = {1873-1635},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss worldwide, driven by complex interactions within the photoreceptor-retinal pigment epithelium (RPE)-choroid unit. Understanding these processes requires integrating in vivo imaging with histopathological evidence, as each provides complementary insights into disease mechanisms. Historically, landmark discoveries-including the characterization of drusen, RPE alterations, and the introduction of optical coherence tomography (OCT)-have led to major paradigm shifts in the diagnosis and management of AMD. Recent advances in multimodal imaging, particularly OCT and OCT angiography (OCTA), have enabled high-resolution, non-invasive visualization of structural and vascular changes, facilitating the identification of clinically relevant biomarkers. When interpreted in the context of histology, these imaging findings have significantly advanced our understanding of AMD pathogenesis, revealing dynamic interactions between neuronal degeneration, outer retinal dysfunction, and vascular impairment. In this review, we synthesize key imaging features of AMD alongside their histopathological correlates, highlighting how this integrative approach has refined disease classification, improved prognostic assessment, and informed therapeutic strategies. We further discuss emerging imaging technologies and their potential to bridge the gap between tissue-level pathology and clinical practice. By linking historical insights with contemporary advances, this review provides a comprehensive framework for understanding AMD and its management.},
}

@article {pmid42104267,
year = {2026},
author = {Okonkwo, ON and Hassan, AO and Oronsaye, DA and Emelumadu, C and Akanbi, T and Agweye, C},
title = {Compliance to intravitreal anti-vascular endothelial growth factors for treatment of retinal diseases in Nigerians: a retrospective multicenter study.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04880-z},
pmid = {42104267},
issn = {1471-2415},
abstract = {BACKGROUND: Little is known about compliance with intravitreal anti-vascular endothelial growth factor (VEGF) therapy for the treatment of macular and retinovascular diseases among Nigerians and Africans. The objective of this study is to measure compliance to 3 or more and 6 or more intravitreal anti-VEGF injections for common macular and retinovascular diseases in Nigerian clinics and evaluate the impact on visual outcomes.

METHOD: Retrospective multicenter chart review of 622 eyes/ 528 patients diagnosed with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusions (RVOs), including branch, central, and hemiretinal (BRVO, CRVO, and HRVO), and non-AMD Choroidal Neovascular Membrane (CNVM) from five clinics (urban, semi-urban, and rural), collecting demographics, diagnosis, injection type/number, pre-/post-BCVA (converted to LogMAR), and follow-up. Treatments were intravitreal Bevacizumab (Avastin), Ranibizumab (Patizra), and Aflibercept (Eylea). Definitions of compliance: compliant; ≥3 injections (standard loading), also ≥ 6 injections.

RESULTS: For all 622 eyes, presenting BCVA: 1.21 ± 0.84 and the final BCVA: 0.91 ± 0.80 (P = < 0.001). Overall compliance with ≥ 3 injections was 47.5%, and with ≥ 6 injections, 10.1%. Compliance to ≥ 3 injections by diagnosis was as follows: AMD 50.4%, Non-AMD CNVM 58.2%, BRVO 44.8%, CRVO 44.0%, HRVO 46.7%, DME 40.6%. Age (P = 0.264) and sex (P = 0.870) did not affect compliance to ≥ 3 injections. Clinic location significantly influenced compliance with ≥ 3 injections (P = 0.000), but not with 6 injections (P = 0.173). The highest rates of compliance with ≥ 3 injections were observed in urban tertiary centers. Injection type and cost were not significant factors (P = 0.36). Eyes with ≥ 3 injections achieved better vision (≥ 6/18) across all diagnoses; the most notable improvements were in non-AMD CNVM (+ 41.4%) and BRVO (+ 35%). Statistically significant LogMAR improvements were seen in CRVO (p = 0.049) and DME (p = 0.043). Postoperative endophthalmitis occurred in 2/622 eyes (0.0032) (both Avastin); no other serious adverse event was recorded.

CONCLUSIONS: Real-world compliance is significantly lower than ideal. Urban and tertiary clinics show better adherence. Receiving the recommended loading doses is associated with improved visual outcomes for most diagnoses. Understanding the reasons for non-compliance, using a prospective approach, and addressing them will improve treatment outcomes for more Nigerian and presumably African patients receiving anti-VEGF drugs.},
}

@article {pmid42104825,
year = {2026},
author = {Gama-Castro, A and Ferrão-Mendes, A and Rodrigues, R and Figueiredo, I and Bragança, F and Laiginhas, R and Cunha, AM and Lume, M and Silva, R and Carneiro, Â},
title = {[Value-Based Healthcare in the Treatment of Age-Related Macular Degeneration: Clinical and Patient-Reported Outcomes from a Portuguese Multicenter Study].},
journal = {Acta medica portuguesa},
volume = {39},
number = {5},
pages = {332-339},
doi = {10.20344/amp.24246},
pmid = {42104825},
issn = {1646-0758},
mesh = {Humans ; Female ; Prospective Studies ; Male ; Aged, 80 and over ; *Patient Reported Outcome Measures ; *Macular Degeneration/drug therapy/therapy ; Aged ; Portugal ; Intravitreal Injections ; Value-Based Health Care ; },
abstract = {INTRODUCTION: This study aimed to describe and compare patient-reported outcome measures (PROMs) and objective clinical outcome measures (CROMs) in the treatment of age-related macular degeneration (AMD), exploring the concordance between these measures within a value-based healthcare (VBH) framework.

METHODS: This prospective, multicenter, observational, real-world study was conducted at three tertiary referral hospitals specializing in the treatment of neovascular AMD. Clinical outcomes (CROMs) and patient-reported outcomes (PROMs) were analyzed using the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25) questionnaire as a functional assessment tool. Data were collected at baseline and at three, six, and 12 months following initiation of intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Statistical analysis was primarily descriptive. The comparison between baseline and 12 months in the global NEI VFQ-25 score was performed using the Wilcoxon signed-rank test for paired samples. Concordance between CROMs and PROMs was assessed using the intraclass correlation coefficient (ICC).

RESULTS: A total of 235 eyes were included, receiving 2338 intravitreal injections. The mean age of participants was 81 years (SD = 8.57), and 55.8% were female. The mean baseline NEI VFQ-25 score was 67.83 (SD = 10.39). The median best-corrected visual acuity was 63 ETDRS letters (interquartile range [P25 - P75]: 41 - 75) at baseline, increasing to 65 letters at three months and remaining stable through 12 months of follow-up. The comparison between baseline and 12 months revealed a statistically significant difference in visual acuity (Wilcoxon signed-rank test, Z = 4.2; p < 0.001). A reduction in the proportion of patients classified as legally blind was observed, together with an increase in the proportion of patients in the reading-vision and driving-vision categories. At 12 months, 58.7% of patients reported stabilization or improvement in visual function on the NEI VFQ-25 questionnaire. Concordance between the variation in visual acuity and the variation in the global NEI VFQ-25 score showed good agreement between CROMs and PROMs (ICC = 0.76; p < 0.001).

CONCLUSION: The integrated analysis of CROMs and PROMs suggests that anti-VEGF treatment for neovascular AMD is associated with stabilization or improvement in visual acuity and patients' perceived visual function. The implementation of the VBH-AMD model proved feasible in a real-world clinical setting, reinforcing the importance of integrating patient-centered measures into the evaluation of therapeutic outcomes.},
}

Humans
Female
Prospective Studies
Male
Aged, 80 and over
*Patient Reported Outcome Measures
*Macular Degeneration/drug therapy/therapy
Aged
Portugal
Intravitreal Injections
Value-Based Health Care

@article {pmid42105087,
year = {2026},
author = {Avram, O and Shwartz, Y and Green, A and Bloom, R and Corradetti, G and Wu, A and Chen, ZJ and Lior, TE and Durmus, B and Rudas, A and Pal, R and Rakocz, N and Soylu, C and Alhelaly, M and Boscia, G and Wykoff, CC and Cannesson, M and Sadda, SR and Levy, J and Halperin, E and Chiang, JN and Chowers, I and Tiosano, L},
title = {A deep learning model for automated identification of age-related macular degeneration atrophy.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42105087},
issn = {1435-702X},
abstract = {Age-related macular degeneration (AMD), a leading cause of visual impairment and blindness among the elderly, is projected to affect 288 million individuals globally by 2040. Advanced AMD, including complete retinal pigment epithelium and outer retinal atrophy (cRORA), pose significant challenges for diagnosis and monitoring due to the labor-intensive, costly, and variable nature of manual annotation of volumetric optical coherence tomography (OCT) scans. Automating cRORA diagnosis offers the potential to improve annotation consistency and reduce clinical burden, which could facilitate, for example, the evaluation of recently FDA-approved treatments that delay disease progression. In this study, we compiled two large independent cohorts totaling nearly 5,000 3D OCT scans, labeled them for cRORA presence, and developed a deep learning model for cRORA automated detection. The model achieved state-of-the-art performance, with a ROC AUC of 0.97 on internal validation, and demonstrated robust translatability (zero-shot learning) with a ROC AUC of 0.88 on external evaluation. Notably, it exhibited high accuracy for both non-neovascular (non-nv) and neovascular (nv) AMD subgroups (ROC AUC 0.98 and 0.93, respectively), including complex cases with exudation. This model and dataset combination could facilitate clinical research and trial analyses by providing scalable, standardized assessments across non-nv and nv AMD patient subgroups.},
}

@article {pmid42105126,
year = {2026},
author = {Turan, L and Bjerager, J and Subhi, Y and Klefter, ON and Hajari, JN and Schneider, M},
title = {Durability of Three Monthly Loading Doses with Faricimab in Treatment-Naïve Neovascular Age-Related Macular Degeneration.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42105126},
issn = {2193-8245},
abstract = {INTRODUCTION: Understanding the durability of faricimab with three monthly loading injections in a real-world clinical setting is important for optimizing treatment intervals and reducing the treatment burden. The aim of this study was to evaluate the durability and visual outcomes of a loading dose regimen consisting of three consecutive monthly faricimab injections in treatment-naïve patients with neovascular age-related macular degeneration (nAMD).

METHODS: This is a retrospective, single-center cohort study using chart review and an electronic injection database, including treatment-naïve patients with nAMD aged 50 years or older who received three monthly faricimab injections between 1 November 2023 and 31 August 2024.

RESULTS: Overall, 827 eyes of 742 patients were included in the study. Following the loading dose, the median injection-free interval was 15.0 weeks (95% confidence interval [CI] 13.1 to 16.6). The estimated injection-free survival probabilities at 4, 6, 8, 10, 12, 14, 16, and 24 weeks were 90.9%, 81.1%, 79.1%, 75.5%, 57.1%, 51.1%, 48.6%, and 29.4%, respectively. At 180 days, 28.4% (n = 235) of eyes remained injection-free, and 21.6% (n = 179) were discharged from hospital-based care. At 4 weeks post-loading, 42.6% of eyes showed improved best-corrected visual acuity (BCVA), 46.3% were stable, and 11.1% declined. The mean BCVA change was -0.082 logarithm of the minimum angle of resolution (logMAR) (95% CI -0.097 to -0.067; p < 0.001), corresponding to a gain of approximately 4 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters.

CONCLUSIONS: A three-injection loading dose regimen of faricimab demonstrated favorable durability, with most eyes maintaining a long injection-free interval and experiencing visual improvement or stability. A routine follow-up at 4 weeks after loading may be unnecessary in many patients, whereas 8 weeks appear adequate. Treatment after loading can be paused for an extended period in a substantial subset of patients. Faricimab may reduce treatment burden early, while providing stabilization or improvement of visual acuity for the majority of patients with nAMD in clinical practice.

TRIAL REGISTRATION: ClinicalTrials.gov registration no. NCT06890026; date of registration: 16 March 2025 (retrospectively registered).},
}

@article {pmid42105376,
year = {2026},
author = {Mang, K and Eichenbaum, D and Vakharia, P},
title = {Geographic atrophy: From slowing lesions to preserving vision.},
journal = {Current opinion in ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1097/ICU.0000000000001224},
pmid = {42105376},
issn = {1531-7021},
abstract = {PURPOSE OF REVIEW: Geographic atrophy, the advanced form of dry age-related macular degeneration (AMD), has historically been evaluated using structural endpoints and best-corrected visual acuity (BCVA). This review examines the growing rationale for a function-first approach.

RECENT FINDINGS: Emerging data demonstrate that functional deficits often decline earlier and more profoundly than BCVA. Recently approved complement inhibitors have shown slowing of geographic atrophy lesion growth but without consistent improvements in traditional visual acuity endpoints. Extension studies and post hoc analyses suggest some functional benefits. Next-generation therapies are increasingly incorporating functional endpoints into trial design.

SUMMARY: Structural slowing alone does not fully capture therapeutic value in geographic atrophy. Functional measures provide a more sensitive and patient-centered assessment of disease progression and treatment impact.},
}

@article {pmid42106176,
year = {2026},
author = {Joo, JH and Jidigam, V and Rao, S},
title = {Retinal angiogenesis: Development and pathophysiology.},
journal = {Handbook of clinical neurology},
volume = {217},
number = {},
pages = {179-201},
doi = {10.1016/B978-0-443-22193-4.00005-6},
pmid = {42106176},
issn = {0072-9752},
mesh = {Humans ; Animals ; *Retinal Neovascularization/physiopathology/pathology ; *Retinal Vessels/physiopathology/pathology ; *Retina/growth & development/pathology/physiopathology ; *Neovascularization, Pathologic/physiopathology/pathology ; Angiogenesis ; },
abstract = {Retinal angiogenesis is the process of new blood vessel formation within the retina, the light-sensitive tissue located at the back of the eye. It is a tightly regulated physiologic process essential for supplying oxygen and nutrients to retinal cells, supporting their metabolic needs, and maintaining overall retinal function. During retinal angiogenesis, new blood vessels sprout from pre-existing vessels in response to specific signals and cues within the retinal microenvironment. The process involves a series of coordinated events, including endothelial cell proliferation, migration, tube formation, and vessel maturation. The process of retinal angiogenesis is tightly regulated by a complex interplay of proangiogenic and antiangiogenic factors, including growth factors, cytokines, extracellular matrix components, and cell-cell signaling pathways. In addition to its role in normal retinal development, angiogenesis in the retina can also occur under pathologic conditions, leading to the formation of abnormal blood vessels. Conditions such as diabetic retinopathy, retinopathy of prematurity, and age-related macular degeneration are characterized by aberrant retinal angiogenesis, which can result in vision-threatening complications. Understanding the mechanisms that regulate retinal angiogenesis is essential for developing novel therapeutic strategies aimed at promoting normal vascular development, inhibiting pathologic angiogenesis, and preserving vision in patients with retinal vascular disorders.},
}

Humans
Animals
*Retinal Neovascularization/physiopathology/pathology
*Retinal Vessels/physiopathology/pathology
*Retina/growth & development/pathology/physiopathology
*Neovascularization, Pathologic/physiopathology/pathology
Angiogenesis

@article {pmid42106177,
year = {2026},
author = {Navratil, EM and Mullins, RF},
title = {Vasculature: Choroid.},
journal = {Handbook of clinical neurology},
volume = {217},
number = {},
pages = {203-217},
doi = {10.1016/B978-0-443-22193-4.00003-2},
pmid = {42106177},
issn = {0072-9752},
mesh = {Humans ; *Choroid/blood supply/anatomy & histology ; Animals ; },
abstract = {The choroid is the highly vascularized connective tissue compartment exterior to the outer blood retinal barrier, which resides between the RPE and the sclera and is the main vascular supply for the retinal pigment epithelium and photoreceptor cells. This review summarizes the structure, innervation, vascular supply, and cell types of the human choroid in both healthy and disease eyes. Special attention is paid to the choriocapillaris and its biochemical and molecular changes in aging and atrophic macular degeneration.},
}

Humans
*Choroid/blood supply/anatomy & histology
Animals

@article {pmid42106178,
year = {2026},
author = {Zaydon, Y and Ahmed, F and Tsang, S},
title = {Genetics of the retina.},
journal = {Handbook of clinical neurology},
volume = {217},
number = {},
pages = {21-33},
doi = {10.1016/B978-0-443-22193-4.00012-3},
pmid = {42106178},
issn = {0072-9752},
mesh = {Humans ; *Retina/pathology ; *Retinal Diseases/genetics ; *Mutation/genetics ; Animals ; },
abstract = {The retina is a vital component of the visual system, converting light into neural signals processed by the brain. Its structure includes photoreceptors, bipolar cells, and ganglion cells, each contributing to vision. Genetics play a critical role in retinal development and health, with mutations in over 270 genes linked to inherited retinal diseases, such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Leber congenital amaurosis (LCA). These conditions range from mild visual impairment to complete blindness, reflecting the genetic diversity underlying retinal diseases. Progress in molecular biology has improved understanding of how genetic mutations disrupt retinal function. For example, RP involves mutations in RHO, USH2A, and RPGR, leading to progressive photoreceptor degeneration. AMD is associated with variations in CFH and ARMS2, driven by both genetic and environmental factors. Next-generation sequencing and gene therapy have enabled more targeted treatments. Continued research into retinal implants, pharmacologic interventions, and mitochondrial therapies is expanding therapeutic options, providing hope for improved outcomes and preservation of vision in individuals with these genetic conditions.},
}

Humans
*Retina/pathology
*Retinal Diseases/genetics
*Mutation/genetics
Animals

@article {pmid42106184,
year = {2026},
author = {Liu, T and Tsui, JC and Vanderbeek, BL},
title = {Epidemiology of retinal disease.},
journal = {Handbook of clinical neurology},
volume = {217},
number = {},
pages = {3-19},
doi = {10.1016/B978-0-443-22193-4.00009-3},
pmid = {42106184},
issn = {0072-9752},
mesh = {Humans ; *Retinal Diseases/epidemiology ; Risk Factors ; Prevalence ; Incidence ; },
abstract = {Age-related macular degeneration (AMD), diabetic retinal disease (DRD), retinal vascular occlusion, retinal detachment, pathologic myopia, macular hole, and epiretinal membrane are major causes of blindness and visual impairment globally. Studies on the epidemiology of these retinal diseases exhibit significant heterogeneity in terms of study design, population, timeframe, and disease definition. Recent data suggest increases in the prevalence and/or incidence of AMD, DRD, retinal vein occlusion, and pediatric myopia, but projecting the future epidemiologic burden of these disorders is difficult due to the disparate impact of demographic, diagnostic, and treatment-associated changes. This chapter reviews the epidemiology of these major retinal diseases with a focus on prevalence, incidence, risk factors, and associations, and highlights areas of need for further research.},
}

Humans
*Retinal Diseases/epidemiology
Risk Factors
Prevalence
Incidence

@article {pmid42106387,
year = {2026},
author = {Balaha, HM and Azam, MT and Mahmoud, A and Ghazal, M and El-Baz, A},
title = {Advanced computer-aided diagnosis for age-related macular degeneration: integrating segmentation and feature extraction for precise diagnosis.},
journal = {Scientific reports},
volume = {},
number = {},
pages = {},
doi = {10.1038/s41598-026-46569-9},
pmid = {42106387},
issn = {2045-2322},
abstract = {Age-related Macular Degeneration (AMD) is a leading cause of vision loss globally; necessitating early detection and precise diagnosis for effective intervention. This study presents a computer-aided diagnosis (CAD) system for AMD detection and diagnosis over two main stages; that are SegNet-MobileNet for segmentation and feature extraction for classification. The SegNet-MobileNet architecture merges the SegNet's precise segmentation with the MobileNet's efficacy; achieving high accuracy in delineating AMD lesions from retinal images. Also, the features extracted from regions of interest (ROIs) capture diverse aspects of retinal structure and texture mandatory for the AMD diagnosis. A dataset of 864 retinal images (accompanied by detailed demographic and clinical information) was collected and analyzed. Through the proper evaluation of ML algorithms, we reported that ensemble methods (such as CatBoost, Extra Trees, and XGBoost) demonstrate superior performance in distinguishing AMD cases, with accuracies exceeding 97%. Model explainability is utilized through the SHapley Additive exPlanations (SHAP) technique; providing insights into feature importance and model decision-making. This study demonstrates the potential of advanced methodologies in contributing to AMD diagnosis and laying the groundwork for future research directions in the ophthalmic imaging and diagnostic field. While promising, these results indicate the need for larger, multi-center validation to ensure generalizability.},
}

@article {pmid42106726,
year = {2026},
author = {Saturno, MC and Gagliardi, OM and La Cava, M and Armentano, M and Alisi, L and Giovannetti, F and Iannetta, D},
title = {Fellow-eye herpes simplex virus type 1 uveitis after intravitreal bevacizumab: a case report.},
journal = {BMC ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12886-026-04872-z},
pmid = {42106726},
issn = {1471-2415},
abstract = {BACKGROUND: Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy is widely used for neovascular retinal diseases. Intraocular inflammation is a recognized adverse event and typically occurs in the injected eye. Inflammation in the fellow, uninjected eye is exceptionally rare and may be misinterpreted as sterile immune-mediated inflammation, potentially delaying appropriate treatment. We report a case of polymerase chain reaction (PCR)-confirmed herpes simplex virus type 1 (HSV-1) uveitis presenting in the fellow eye shortly after intravitreal bevacizumab administration.

CASE PRESENTATION: An 84-year-old man with well-controlled type 2 diabetes mellitus received intravitreal bevacizumab (1.25 mg) in the left eye for neovascular age-related macular degeneration. Three days later, he developed acute granulomatous anterior uveitis with dense vitritis in the right, uninjected eye, while the treated eye remained quiescent. Best-corrected visual acuity decreased to 20/400. Given the severity of inflammation and limited fundus visualization, viral retinitis was suspected. Empirical systemic valacyclovir and topical corticosteroids were initiated. Aqueous humor PCR detected HSV-1 DNA, confirming herpetic uveitis. Inflammation resolved within 40 days with recovery of visual acuity to 20/20 and no progression to acute retinal necrosis. The patient remained recurrence-free under antiviral prophylaxis at last follow-up.

CONCLUSIONS: Severe fellow-eye inflammation following intravitreal bevacizumab may reflect viral reactivation rather than sterile inflammation. Early diagnostic evaluation, including aqueous humor PCR when clinically indicated, is essential to guide appropriate therapy and prevent sight-threatening complications.},
}

@article {pmid42106786,
year = {2026},
author = {Hall, JC and Krishna Sudhakar, K and Daniszewski, M and Senabouth, A and Abbott, CJ and Liang, HH and Kumar, H and Lidgerwood, GE and Mirzaei, M and Ma, JY and Atkeson, T and Hirokawa, Y and Nandrot, EF and Barnett, A and Cazevieille, C and Manes, G and Mountford, S and Thompson, P and Fletcher, EL and Wu, Z and Bahlo, M and Ansell, BRE and Paull, D and Hewitt, AW and Guymer, RH and Powell, JE and Pébay, A},
title = {Patient induced pluripotent stem cells identify specificities of a reticular pseudodrusen phenotype in age-related macular degeneration.},
journal = {Genome medicine},
volume = {18},
number = {1},
pages = {},
pmid = {42106786},
issn = {1756-994X},
}

@article {pmid42103449,
year = {2026},
author = {Riedl, S and Mai, J and Enzendorfer, ML and Nugawela, MD and Fritsche, L and Prevost, T and Rueckert, D and Menten, M and Scholl, H and Sivaprasad, S and Lotery, A and Bogunovic, H and Sacu, S and Schmidt-Erfurth, U},
title = {OCT-based AI-assisted phenotyping of intermediate AMD in the prospective PINNACLE trial: PINNACLE Study Report 9.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-327938},
pmid = {42103449},
issn = {1468-2079},
abstract = {BACKGROUND/AIMS: PINNACLE is one of the largest prospective multicentre observational studies evaluating the progression of intermediate age-related macular degeneration (iAMD). This paper aims to provide an optical coherence tomography (OCT)-based qualitative and quantitative characterisation of the cohort's baseline morphology.

METHODS: Based on expert grader readings and artificial intelligence (AI)-based image analysis, we report the prevalence, quantitative measurements, topographic distribution and intercorrelation of characteristic iAMD features including drusen, drusen subtypes, subretinal drusenoid deposits (SDD), hyperreflective foci (HRF), double layer sign and various measurements of outer retinal condition, such as ellipsoid zone (EZ) and outer nuclear layer (ONL) thicknesses, incomplete retinal pigment epithelium and outer retinal atrophy (iRORA) and a semi-automated atrophic marker including EZ loss and choroidal hypertransmission (EZLHT).

RESULTS: Drusen accumulate within the central 3 mm while SDD predominantly occurs in the superior perifoveal quadrant. Whereas higher drusen volume was associated with the presence and volume of HRF, it was inversely correlated with SDD presence. Thickness measurements of the EZ and ONL demonstrate outer retinal thinning, indicating photoreceptor compromise in iAMD, more pronounced in eyes showing atrophic features such as iRORA or EZLHT.

CONCLUSION: This work combines expert grader readings with AI-based image analyses, applied on the largest prospectively, densely OCT-imaged cohort of iAMD reported on so far. The results show feature distribution comparable to previous reports. They substantially contribute to the comprehensive morphological characterisation of iAMD. This data is relevant for the interpretation of longitudinal data, refining inclusion criteria for future clinical trials and for providing a reference to other trials in the field.},
}

@article {pmid42095312,
year = {2026},
author = {Wartenberg, PJ and Jensen, AN and Thomsen, AK and Sørensen, TL},
title = {Geographical disparities in visual acuity at diagnosis among patients with neovascular age-related macular degeneration.},
journal = {Danish medical journal},
volume = {73},
number = {5},
pages = {},
doi = {10.61409/A05250419},
pmid = {42095312},
issn = {2245-1919},
mesh = {Humans ; Male ; Female ; Retrospective Studies ; *Visual Acuity ; Denmark/epidemiology ; Aged ; Aged, 80 and over ; Middle Aged ; *Macular Degeneration/diagnosis ; *Wet Macular Degeneration/diagnosis/physiopathology ; },
abstract = {INTRODUCTION: Neovascular age-related macular degeneration (nAMD) affects approximately 8% of the global population. While socioeconomic and geographical disparities have been increasingly studied in Denmark, geographical disparity in best corrected visual acuity (BCVA) at the time of diagnosis in nAMD remains understudied. This study aimed to investigate possible geographical disparity in BCVA at the time of diagnosis in nAMD patients in Region Zealand, Denmark.

METHODS: This was a retrospective study using data from the database "Bedre Oftalmologi for Brugere" from 2011 to 2021. BCVA was extracted for patients at the time of diagnosis with nAMD. Patients were grouped geographically by postal code and municipality. Data were analysed using the Kruskal-Wallis test to investigate geographical disparity and stratified by sex.

RESULTS: A total of 4,266 eyes with nAMD were included. Variations in BCVA at the time of nAMD diagnosis were found between geographical regions in Region Zealand at postal code level and at municipality level. Furthermore, we found a disparity between municipalities among males and females. However, no statistically significant disparity between postal codes was found among males or females.

CONCLUSIONS: There was a significant geographical disparity in BCVA at the time of diagnosis in nAMD patients, inviting further investigation to determine the extent and roots of this disparity.

FUNDING: None.

TRIAL REGISTRATION: Not relevant.},
}

Humans
Male
Female
Retrospective Studies
*Visual Acuity
Denmark/epidemiology
Aged
Aged, 80 and over
Middle Aged
*Macular Degeneration/diagnosis
*Wet Macular Degeneration/diagnosis/physiopathology

@article {pmid42097863,
year = {2026},
author = {Chi, K and He, Y and Zuo, X and Lai, C and Cao, J and Ying, Y and Zhang, B and Li, R and Chen, M and Tan, X and Li, Q and Wang, S and Wu, Q and He, J and Liu, L and Hu, Y and Zhu, Z and Zhang, X and Yu, H},
title = {Linking accelerated biological ageing to cataract susceptibility: evidence from cross-cohort analysis.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329061},
pmid = {42097863},
issn = {1468-2079},
abstract = {PURPOSE: The cross-sectional and longitudinal associations between accelerated biological ageing and the risk of cataract and other blinding eye diseases (including glaucoma and age-related macular degeneration (AMD)) remain unclear.

METHODS: We included participants aged 40 and above with biological ages, including phenotypic age (PhenoAge), Klemera-Doubal method (KDMAge) and retinal age (RetiAge), from the US National Health and Nutrition Examination Survey (NHANES) and UK Biobank. The cross-sectional analyses were conducted to identify associations of PhenoAge or KDMAge acceleration with cataract and other blinding eye diseases using logistic regression. In a prospective UK cohort, we explored the relationships between the acceleration of PhenoAge, KDMAge or RetiAge and cataract and other blinding eye diseases using the Cox proportional hazards model.

RESULTS: This study consisted of 5433 participants from the US NHANES and 269 615 participants from the UK Biobank. In both cross-sectional and longitudinal analyses, accelerated biological ageing was positively associated with an increased risk of cataract (all p<0.05). In a longitudinal cohort, RetiAge acceleration demonstrated the larger effect size estimates (HR 1.54 (95% CI 1.38 to 1.73)) compared with PhenoAge acceleration (HR 1.05 (95% CI 1.03 to 1.08)) and KDMAge acceleration (HR 1.06 (95% CI 1.04 to 1.08)). Only in the UK population, risks of glaucoma showed stronger links with KDMAge acceleration (HR 1.06 (95% CI 1.01 to 1.11)), while AMD showed more pronounced associations with PhenoAge acceleration (HR 1.08 (95% CI 1.02 to 1.14)).

CONCLUSIONS: Accelerated biological ageing might represent a potential target of assessment and intervention for cataract.},
}

@article {pmid42100539,
year = {2026},
author = {Zou, H and Li, D and Wang, X and Yu, L and Yang, B and Luo, L and Xiao, J},
title = {Knowledge, attitude and practice of patients and their family members regarding age-related macular degeneration: a cross-sectional study.},
journal = {Frontiers in public health},
volume = {14},
number = {},
pages = {1811521},
pmid = {42100539},
issn = {2296-2565},
mesh = {Humans ; Cross-Sectional Studies ; *Health Knowledge, Attitudes, Practice ; *Macular Degeneration/therapy/psychology ; Female ; Male ; *Family/psychology ; Aged ; Surveys and Questionnaires ; Middle Aged ; Adult ; Aged, 80 and over ; China ; },
abstract = {INTRODUCTION: Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the older adults, and understanding the knowledge, attitudes, and practices (KAP) of patients and their family members is essential for improving disease management and patient education. This study aimed to assess the knowledge, attitudes, and practices (KAP) of patients with age-related macular degeneration (AMD) and their family members.

METHODS: A cross-sectional survey was conducted between April and July 2023 at the Department of Ophthalmology, the Second Hospital of Jilin University, using a self-administered questionnaire.

RESULTS: A total of 538 valid questionnaires were included in the analysis, comprising 325 patients (60.41%) and 213 family members (39.59%). Among all participants, 495 (92.01%) reported having undergone intraocular injection therapy, while 43 (7.99%) had not received such treatment. The mean KAP scores were 10.99 ± 1.30 for knowledge, 43.05 ± 3.48 for attitude, and 22.36 ± 3.96 for practice. Significant positive correlations were observed between knowledge and attitude, knowledge and practice, and attitude and practice. Structural equation modeling further demonstrated that knowledge had a significant direct effect on attitude, and attitude had a significant direct effect on practice, with attitude fully mediating the relationship between knowledge and practice.

DISCUSSION: Overall, patients and their family members exhibited adequate knowledge of AMD, whereas attitude and practice levels were moderate. These findings highlight the need for targeted educational interventions to enhance AMD-related knowledge, foster positive attitudes through supportive patient-family interactions, and facilitate the translation of knowledge and attitudes into appropriate health-related behaviors, with particular emphasis on timely medical consultation and adherence to treatment.},
}

Humans
Cross-Sectional Studies
*Health Knowledge, Attitudes, Practice
*Macular Degeneration/therapy/psychology
Female
Male
*Family/psychology
Aged
Surveys and Questionnaires
Middle Aged
Adult
Aged, 80 and over
China

@article {pmid42100984,
year = {2026},
author = {Wolf, A and Clahsen, T and Langmann, T},
title = {The role of human complement factor H in retinal immune response and the prospects for targeted therapy for age-related macular degeneration (AMD).},
journal = {Expert opinion on therapeutic targets},
volume = {},
number = {},
pages = {},
doi = {10.1080/14728222.2026.2671685},
pmid = {42100984},
issn = {1744-7631},
}

@article {pmid42102824,
year = {2026},
author = {Brennan, K and Ozaki, E and Noone, E and Palko, S and Byrne, KP and Roche, F and McElheron, M and Byrne, K and Gibbons, L and Robb, K and Aktas, S and Connolly, E and Hudson, N and O'Riordan, MM and O'Boyle, D and Dalton, R and Zoller, A and Fahey, E and Hokamp, K and Feenstra, D and Bourke, N and Campbell, M and Finlay, D and Mulfaul, K and Mullins, RF and Kenny, RA and Cahill, MT and Doyle, SL},
title = {Circulating natural killer cells are phenotypically and functionally altered in age-related macular degeneration.},
journal = {Cell reports. Medicine},
volume = {},
number = {},
pages = {102792},
doi = {10.1016/j.xcrm.2026.102792},
pmid = {42102824},
issn = {2666-3791},
abstract = {Age-related macular degeneration (AMD) is the leading cause of irreversible central blindness and can result in pathological neovascularization. Using a "human-first" approach, we identify immunotherapy as a disease modifier in models of neovascular AMD (nAMD). Plasma cytokine analysis in a large population cohort reveals an imbalance of lymphocytic cytokines associated with severity of AMD, leading to discovery of a skewed peripheral natural killer (NK) cell phenotype in individuals with AMD. Peripheral NK cells are rapidly activated in nAMD models, and single-cell RNA sequencing demonstrates expansion of activated cytolytic NK cells within neovascular lesions during resolution. NK cells localize to neovessels in human AMD donor eyes; however, they exhibit markers of terminal differentiation and quiescence. Adoptive transfer of pre-activated NK cells reduces neovascularization and restores barrier integrity. Our data identify a distinct, functionally altered NK cell phenotype in nAMD and suggests harnessing NK cells represents an immunotherapeutic alternative for the treatment of nAMD.},
}

@article {pmid42103030,
year = {2026},
author = {Sadek, K and Yu, P and Al-Burak, SA and Osman, R and Tao, BK and Al-Ani, A and Ghaseminejad, F and Khan, H and Arjmand, P and Hutnik, C and Navajas, EV},
title = {The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.},
journal = {Survey of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.survophthal.2026.04.007},
pmid = {42103030},
issn = {1879-3304},
abstract = {Our goal is to determine whether adjunctive aqueous suppressants (topical β-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (±timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.},
}

@article {pmid42091216,
year = {2026},
author = {Huang, Z and Su, K and Zhou, L and Du, Y and Li, Y and Zhu, X},
title = {Systemic inflammatory biomarkers as risk factors for age-related ocular diseases: a large-scale prospective cohort study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328553},
pmid = {42091216},
issn = {1468-2079},
abstract = {AIMS: To evaluate associations between systemic inflammation biomarkers and incident age-related ocular diseases while also investigating their correlations with retinal structures.

METHODS: This population-based prospective cohort study analysed 415 599 UK Biobank participants. Systemic immune-inflammation index (SII) and low-grade inflammation score (INFLA-score) were calculated from baseline haematological parameters. Primary outcomes were incident diagnoses of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD) and diabetic retinopathy (DR). Multivariable Cox proportional hazards models estimated HRs with 95% CIs. Secondary analyses assessed the associations with optical coherence tomography-derived retinal layer thicknesses and vascular features.

RESULTS: Over a median 13.0-year follow-up, we identified 44 906 cataract, 5803 POAG, 7388 AMD and 3319 DR incident cases. Both SII and INFLA-score demonstrated significant, dose-dependent associations with all ocular outcomes (all p<0.05). Distinct exposure-response patterns emerged: J-shaped relationships for cataract and POAG (SII threshold >500; INFLA-score threshold >0), versus monotonically positive associations for AMD and DR. Elevated inflammatory markers also correlated with retinal thinning, especially in photoreceptor layers.

CONCLUSIONS: Systemic inflammation biomarkers could predict incident age-related ocular diseases with disease-specific patterns while concurrently associating with quantifiable retinal structural and vascular pathologies. These findings suggest that anti-inflammatory strategies might have potential to mitigate ocular ageing processes, although further evidence on causal mechanisms and interventions is warranted.},
}

@article {pmid42091217,
year = {2026},
author = {Li, Y and Tan, S and Xiong, R and Li, H and Zhu, Z and Chen, S and Wang, W},
title = {Posterior staphyloma and long-term structural and visual trajectories in high myopia.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2026-329468},
pmid = {42091217},
issn = {1468-2079},
abstract = {PURPOSE: To determine whether posterior staphyloma (PS) is associated with long-term trajectories of ocular structural changes, myopia-related complications and visual outcomes in high myopia.

METHODS: This prospective longitudinal cohort study included 614 highly myopic eyes from the Zhongshan High Myopia Cohort Study, followed for up to 12 years. Eyes were categorised by PS status: baseline PS (n=46), new-onset PS (n=94) or no PS (n=474). The associations between PS and myopic macular degeneration (MMD) progression, myopic traction maculopathy (MTM) and plus lesions incidence, longitudinal changes in ocular parameters and incident moderate-to-severe visual impairment (MSVI) were assessed.

RESULTS: PS was independently associated with increased risks of MMD progression (OR 3.39, 95% CI 1.81 to 6.35, p<0.001), MTM (OR 2.25, 95% CI 1.06 to 4.77, p=0.034) and incident plus lesions (OR 3.15, 95% CI 1.16 to 8.57, p=0.024). The highest risks of MTM and plus lesions were observed in eyes with new-onset PS. Eyes with PS demonstrated significantly faster axial elongation (mean annual rate: baseline PS, 0.120 mm (95% CI 0.099 to 0.142); new-onset PS: 0.129 mm (95% CI 0.114 to 0.145); no PS: 0.066 mm (95% CI 0.060 to 0.073), p<0.001) and a fivefold higher risk of MSVI (95% CI 1.36 to 18.45, p=0.016).

CONCLUSIONS: PS marks a pivotal structural transition in high myopia, identifying a phase of accelerated axial elongation, increased risk of complications and worse visual outcomes, and may serve as a key marker for risk stratification and an important target for early intervention.},
}

@article {pmid42093552,
year = {2026},
author = {Huang, Y and Zhu, X and Lu, R and Jiang, K and Zhu, L and Zhou, X and Hong, J and Zhang, C},
title = {Retina-targeted siRNA delivery via exosome-liposome hybrid vesicles for AMD treatment.},
journal = {Biomaterials science},
volume = {},
number = {},
pages = {},
doi = {10.1039/d6bm00090h},
pmid = {42093552},
issn = {2047-4849},
abstract = {Effective treatment of neovascular age-related macular degeneration (AMD) requires targeted inhibition of vascular endothelial growth factor (VEGF) within the retina. However, delivering therapeutic siRNA to the retinal pigment epithelium (RPE), a key source of pathogenic VEGF, remains a major challenge due to ocular barriers and poor cellular tropism. To address this, we developed a retina-targeted delivery system by engineering exosome-liposome hybrid vesicles that encapsulate VEGF-silencing siRNA (Hybrid-siVEGF). The hybrid design leverages the innate homing capability of RPE-derived exosomes for retinal targeting, combined with the high siRNA loading capacity of synthetic liposomes. In vitro, Hybrid-siVEGF showed significantly enhanced uptake by human RPE cells compared to conventional liposomes, leading to the potent and specific knockdown of VEGF expression and the subsequent inhibition of endothelial cell proliferation. In vivo, a single intravitreal injection of Hybrid-siVEGF in a laser-induced choroidal neovascularization mouse model resulted in efficient accumulation within the retina, significant suppression of pathological angiogenesis, preservation of retinal morphology, and restoration of visual function. Our work establishes exosome-liposome hybrids as an effective and targeted platform for ocular siRNA delivery, offering a promising strategy for RNAi-based therapy for AMD and other retinal disorders.},
}

@article {pmid42094155,
year = {2026},
author = {Sun, X and You, S and Sun, S and Cai, CX and Abraham, J and Yen, PY and Zhang, L},
title = {One Size Fits All? Comparing Foundation and Task-specific Models for Retinal Fluid Segmentation.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
doi = {10.64898/2026.04.26.26351792},
pmid = {42094155},
abstract = {Retinal fluids, detectable through optical coherence tomography (OCT), are key biomarkers for retinal diseases such as diabetic macular edema and age-related macular degeneration, guiding treatment decisions and monitoring response to therapy. Automated segmentation of retinal fluids could support large-scale clinical research and the development of clinical decision support tools. Recent ophthalmic foundation models trained on massive retinal imaging datasets show promise across many downstream tasks, including disease risk prediction and biomarker segmentation, but their performance relative to task-specific models for specialized clinical tasks remains unclear. We compared a task-specific segmentation model (RetiFluidNet) and an ophthalmic foundation model (VisionFM) using a standard benchmarking dataset containing 4,248 OCT images from 48 patients with three retinal diseases. Models were evaluated using three-fold cross-validation and assessed for pixel-level segmentation accuracy and patient-level fluid burden estimation. The task-specific model achieved higher segmentation performance and more consistent fluid quantification across devices. These findings suggest that, for retinal fluid segmentation, specialized task-specific models currently remain more reliable than general-purpose foundation models, highlighting the need for targeted adaptation before clinical deployment.},
}

@article {pmid42086315,
year = {2026},
author = {Cheng, S and Han, R and Zhang, W and Meng, L and Gu, X and Zhao, X and Chen, Y},
title = {Development and validation of a machine learning model to predict recurrence in polypoidal choroidal vasculopathy: a multicentre prospective study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328228},
pmid = {42086315},
issn = {1468-2079},
abstract = {AIM: This study aims to develop and validate machine learning models for predicting recurrence in polypoidal choroidal vasculopathy (PCV) patients using optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers.

METHODS: This multicentre prospective study was conducted at 14 hospitals between June 2019 and December 2023. Patients who achieved remission after anti-vascular endothelial growth factor treatment were followed up for at least 1 year with serial OCT/OCTA imaging. Predictive features were selected using the least absolute shrinkage and selection operator (LASSO) regression with 10-fold cross-validation. Five classifiers (logistic regression, support vector machine, random forest, k-nearest neighbours and extreme gradient boosting (XGBoost)) were developed and evaluated using area under the curve (AUC), accuracy, sensitivity and specificity. Shapley additive explanations (SHAP) were applied for model interpretation and feature ranking.

RESULTS: A total of 204 eyes were included, with 125 from Peking Union Medical College Hospital (training set) and 79 from 13 other centres across China (external validation set). Ten features were selected for model development. In the external validation set, AUCs ranged from 0.801 to 0.861, with the XGBoost model achieving the highest AUC (0.861). SHAP analysis revealed that the percent change in polyp height, the change in branching neovascular network area and the change in subfoveal choroidal thickness were the top three significant predictors.

CONCLUSION: The XGBoost model demonstrated the best predictive performance, providing a reliable tool for recurrence prediction, aiding personalised treatment decisions and optimising clinical resources.},
}

@article {pmid42086316,
year = {2026},
author = {Shah, P and Farah, HA and Wisotsky, DJ and Nawani, P and Hariharan, S and Satasia, A and Muir, ER and Mian, UK and Duong, TQ},
title = {Classification of retinal diseases based on optical coherence tomography angiography using cross-modal transfer learning of domain-specific foundation AI models.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-329249},
pmid = {42086316},
issn = {1468-2079},
abstract = {AIMS: This study evaluated the use of ophthalmic foundation deep-learning models with cross-modal transfer learning to classify multiple diseases on optical coherence tomography angiography (OCTA) with limited sample size.

METHODS: The OCTA-500 dataset (n=500 subjects) was split into an 85% training/validation set for fivefold cross-validation and a 15% held-out test set. Superficial and deep projections from OCTA were combined using intermediate fusion. Outcomes were multi-disease classification of normal, diabetic retinopathy, age-related macular degeneration and 'other'. Transfer-learning from colour fundus photography was used to overcome the limitation of small sample sizes. Vision-Transformer-VisionFM and Vision-Transformer-RETFound domain-specific foundation models with cross-modal transfer learning were evaluated. Comparison was made with Vision-Transformer-ImageNet, a non-domain-specific model. Performance was evaluated using accuracy, F1-score, precision, recall and area under the receiver operating characteristic curve. Saliency maps were also computed.

RESULTS: VisionFM with cross-modal transfer learning outperformed ImageNet in classifying different diseases on OCTA (accuracy: 0.8133±0.0470 vs 0.7600±0.0502). RETFound with cross-modal transfer learning outperformed ImageNet in classifying different diseases on OCTA (accuracy: 0.8000±0.0507 vs 0.7600±0.0521). Similar conclusions were reached with other performance metrics. Saliency maps from VisionFM and RETFound yielded attention patterns that localised pathology to relevant retinal structures on superficial and deep projections from OCTA, comparing favourably with those from ImageNet models.

CONCLUSIONS: Retinal foundation models with cross-modal transfer learning enable accurate multi-class classification using OCTA data, which had small sample size. Results from domain-specific foundation models compared favourably with a non-domain-specific model. Saliency analysis showed attention patterns of pathology localised to anatomically relevant retinal structures.},
}

@article {pmid42088264,
year = {2026},
author = {Wickman, I and Huzevkova, I and Schroeder, M and Granstam, E and Kjellström, U and Lövestam-Adrian, M},
title = {Visual Acuity and Intraretinal Fluid as Predictive Factors for Legal Blindness and Macular Atrophy in Neovascular AMD Eyes Treated with Anti-VEGF: A Swedish Real-World Study.},
journal = {Clinical ophthalmology (Auckland, N.Z.)},
volume = {20},
number = {},
pages = {579968},
pmid = {42088264},
issn = {1177-5467},
abstract = {PURPOSE: Ocular coherence tomography (OCT) biomarkers have previously been able to predict low visual acuity (VA). The purpose of this study was to identify other OCT predictors for a final VA ≤35 and risk factors for macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD).

METHODS: This retrospective observational study included 107 treatment naïve nAMD eyes who initiated treatment and were followed for 3 years ± 2 months or until VA deterioration to or below 35 ETDRS letters. Eyes with final VA ≤35 letters (low VA group) were compared with those with a final VA >35 letters (maintenance group). Swedish Macula Register (SMR) data and OCT images were analyzed to identify risk factors for MA development and low VA. MA was defined according to the criteria for Complete Retinal Pigment Epithelium and Outer Retinal Atrophy (cRORA), which was based on OCT parameters.

RESULTS: Twenty eyes (19%) were presented with a final VA ≤35 ETDRS letters. Mean time from baseline to ≤35 ETDRS letters was 587.7 ± 330.4 days, with a mean 9.7 ± 5.3 injections during that period. Mean baseline VA in the maintenance group vs the low VA group were 65.4 ± 10.8 and 52.0 ± 10.6, respectively; p <0.001. Lower baseline VA was a predictor for low final VA. At baseline, 87% did not have MA on OCT. Among eyes with at least 1 OCT follow-up value in this group, 25% developed MA during the 3-year period. The presence of intraretinal fluid (IRF) at baseline was a predictor for MA development within 3 years in this subgroup.

CONCLUSION: After 3 years, 19% had declined to VA ≤35 ETDRS letters. About 25% with ≥1 available OCT follow-ups developed MA. Lower baseline VA predicted a final VA ≤35 ETDRS letters in nAMD eyes. IRF at baseline predicted MA. The high prevalence of missing VA values emphasizes the importance of increasing the frequency of VA testing.},
}

@article {pmid42082325,
year = {2026},
author = {Karri, R and Sousa, DC and Hadoux, X and Al-Qureshi, S and Harper, CA and Cohn, AC and Fagan, XJ and Chong, E and Edwards, TL and Lin, ML and Wickremasinghe, S and Chiu, D and Arnold, JJ and Kwan, AS and Campbell, TG and Durkin, SR and Mehta, H and Fraser-Bell, S and Razavi, H and Korobelnik, JF and Lanzetta, P and Holz, FG and Cheung, CMG and Boyer, DS and Balaratnasingam, C and Allen, PJ and Lim, LL and Guymer, R and Van Wijngaarden, P},
title = {Expert consensus on fundus fluorescein angiography reporting in ophthalmology: a Delphi study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2025-328870},
pmid = {42082325},
issn = {1468-2079},
abstract = {PURPOSE: Fundus fluorescein angiography (FFA) is an important tool in evaluating retinal vascular disease. In the era of optical coherence tomography angiography (OCTA), however, expert preferences regarding the comparative utility of FFA and OCTA remain unclear. Additionally, despite FFA's widespread use, variability exists in the terminology used to describe angiographic findings. This study aimed to establish expert consensus on clinical indications for FFA versus OCTA and to provide consensus definitions of key angiographic terms.

METHODS: Using a two-round modified Delphi process, 25 retinal subspecialists provided perspectives on the clinical indications for FFA in the assessment of a range of retinal vascular conditions. They also evaluated proposed definitions for FFA findings in retinal vascular diseases. Consensus was defined as ≥80% agreement and near consensus as 70%-79%.

RESULTS: Experts agreed that FFA is preferable for the diagnosis of retinal vasculitis, ocular ischaemic syndrome and proliferative diabetic retinopathy, even when OCTA is available. Furthermore, FFA was the favoured imaging modality to guide laser photocoagulation in branch retinal vein occlusion. Conversely, FFA was considered non-essential in evaluating neovascular age-related macular degeneration and mild-to-moderate non-proliferative diabetic retinopathy. Finally, definitions were agreed on for seven FFA terms used in the evaluation of retinal vascular diseases. These were non-perfusion, capillary dropout, window defect, pooling, leakage, neovascularisation and staining.

CONCLUSION: This study presents contemporary perspectives on the clinical indications for FFA in an era in which OCT and OCTA are widely available. It also provides a lexicon for FFA reporting in retinal vascular diseases based on expert consensus.},
}

@article {pmid42082781,
year = {2026},
author = {Biagioni, F and Forte, M and di Nonno, F and Busceti, CL and Pinelli, R and Bumah, VV and Ferrucci, M and Lazzeri, G and Sciarretta, S and Frati, G and Fornai, F},
title = {Spontaneous whole retinal degeneration in aged Beclin1 heterozygous mice.},
journal = {Journal of neural transmission (Vienna, Austria : 1996)},
volume = {},
number = {},
pages = {},
pmid = {42082781},
issn = {1435-1463},
abstract = {Retinal degenerative diseases range from rare inherited forms to common multifactorial disorders such as age-related macular degeneration, which is the leading cause of blindness in developed countries. Recent evidence identifies impaired autophagy as a key pathogenetic mechanism. In the disease process alterations of the outer retina start from the retinal pigment epithelium (RPE), to progress downstream in the inner retina leading to widespread whole retinal degeneration. Recent studies indicate that among autophagy-related proteins Beclin1 plays a relevant effect in sustaining retinal integrity, since it is induced by light exposure and it is placed at the intersection between mitophagy, lipophagy, and glycophagy, which are involved during retinal degeneration. The present study was carried out by profiting of BECN1 heterozygous aged mice (BECN+/-), where RT-PCR and western blotting analysis confirmed the loss of both the primary transcript (BECN1) and protein (Beclin1) in the whole retina. Multiple converging techniques indicate a marked degeneration of RPE and photoreceptor layer, where a dismantling of proteins forming tight junction was documented. Inner retinal degeneration was extended within outer and inner nuclear layer. In the inner retina the expression of the detrimental protein alpha synuclein was increased concomitantly with a defect of autophagy markers. The study indicates a seminal role of Beclin1 in maintaining retinal integrity and it defines the vulnerability of various retinal layers in the spreading of Beclin1-dependent retinal degeneration. The potential of increasing the expression of Beclin1 through photobiomodulation is discussed, since it supports retinal integrity when amber/red light-induced stimulation occurs.},
}

@article {pmid42084617,
year = {2026},
author = {Swarn, S and Singh, RK and Sharma, SK and Nasir, N and Wahab, S and Kapoor, DU},
title = {Nanoparticle-mediated targeted delivery of lutein for retinal protection: emerging strategies in ocular drug targeting.},
journal = {Naunyn-Schmiedeberg's archives of pharmacology},
volume = {},
number = {},
pages = {},
pmid = {42084617},
issn = {1432-1912},
support = {RGP1/44/46//Deanship of Research and Graduate Studies at King Khalid University for funding this work through Small Research Project/ ; },
abstract = {Lutein, a key macular carotenoid with potent antioxidant and blue-light-filtering properties, plays a crucial role in maintaining retinal integrity and preventing vision-threatening ocular disorders. However, its clinical efficacy is limited by poor aqueous solubility, instability, low bioavailability, and restricted penetration across ocular barriers. Recent advances in nanotechnology have enabled the development of lutein-loaded nanoparticle systems that significantly improve its stability, solubility, controlled release, and targeted delivery to anterior and posterior eye segments. This review comprehensively summarizes the physicochemical properties of lutein and the limitations of conventional lutein supplementation. The review entails diverse nanocarrier platforms including liposomes, polymeric nanoparticles, solid lipid nanoparticles, nanoemulsions, micelles, and cubosomes highlights their mechanisms of ocular transport, formulation variables, and therapeutic relevance. Emerging evidence demonstrates that lutein-loaded nanoparticles unveil enhanced antioxidant, anti-inflammatory, anti-angiogenic, and cytoprotective effects across multiple ocular pathologies such as age-related macular degeneration, cataract, dry eye disease, blue light-induced retinal degeneration, and retinal pigment epithelial cell injury. Preclinical studies reveal improved retinal uptake, prolonged retention, and superior biological activity compared to free lutein. The lutein-loaded nanoparticles represent a promising next-generation strategy for efficient ocular delivery and targeted management of degenerative and oxidative eye diseases.},
}

@article {pmid42069635,
year = {2026},
author = {Xu, Q and Li, M and Li, D and Dai, X and Zhang, Y and Qu, Y},
title = {3D spheroids of umbilical cord-derived MSCs protect retinal pigment epithelium against oxidative and inflammatory injury by activating autophagy.},
journal = {Stem cell research & therapy},
volume = {},
number = {},
pages = {},
doi = {10.1186/s13287-026-05043-z},
pmid = {42069635},
issn = {1757-6512},
support = {#ZR2025QC1712//Shandong Provincial Natural Science Foundation/ ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is characterized by progressive retinal pigment epithelium (RPE) dysfunction driven by oxidative stress and chronic inflammation, in which NLRP3 inflammasome activation plays a critical role. Mesenchymal stem cells (MSCs) exhibit therapeutic potential, but their efficacy is limited by poor survival and reduced paracrine activity in hostile microenvironments. Here, we investigated whether three-dimensional (3D) spheroid culture enhances the protective effects of umbilical cord-derived MSCs (UC-MSCs) on RPE cells by promoting autophagy and suppressing inflammasome activation.

METHODS: Human UC-MSCs were cultured as 3D spheroids or conventional 2D monolayers and applied in sodium iodate (NaIO3)-induced oxidative injury models both in vitro and in vivo. Retinal morphology and function were assessed via histology and electroretinography, while NLRP3/caspase-1 activation, LC3-II/I ratios, and autophagy flux were quantified using immunofluorescence and Western blot. GO/KEGG enrichment was performed to identify pathways associated with 3D MSCs efficacy. Mechanistic involvement of autophagy was validated using 3-methyladenine (3-MA) and rapamycin.

RESULTS: 3D MSCs formed compact spheroids exhibiting enhanced paracrine potential and significantly outperformed 2D MSCs in protecting RPE cells against NaIO3-induced injury. In vivo, 3D MSC treatment preserved retinal structure, reduced RPE cell loss, and improved retinal function. In vitro, co-culture with 3D MSCs markedly improved ARPE-19 viability, reduced apoptosis, and modulated autophagy-related marker expression, as evidenced by increased LC3-II/I ratios. 3D MSCs significantly inhibited NLRP3 inflammasome activation and pro-inflammatory cytokine release, effects reversed by 3-MA and further enhanced by rapamycin.

CONCLUSIONS: 3D spheroid culture substantially augments the therapeutic efficacy of UC-MSCs by boosting autophagy and suppressing NLRP3 inflammasome signaling, resulting in enhanced protection of RPE cells from oxidative and inflammatory injury. These findings provide preclinical evidence supporting 3D MSCs as a promising therapeutic strategy for AMD.},
}

@article {pmid42070018,
year = {2026},
author = {Agarwal, R and Iezhitsa, I and Hombrebueno, JR and Agarwal, P},
title = {Retinal organoids: current status of development and new avenues for application in disease modeling, drug discovery and therapeutics.},
journal = {International journal of retina and vitreous},
volume = {},
number = {},
pages = {},
doi = {10.1186/s40942-026-00846-x},
pmid = {42070018},
issn = {2056-9920},
abstract = {Visual impairment affects over 2.2 billion people worldwide and the major causes include age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy. For research in these areas, although animal models offer a more physiologically complex system than in vitro approaches, their use raises ethical considerations, and species-specific differences such as variations in protein sequences and signaling pathways. This can limit the direct translatability of the outcomes. Traditional 2-D cell cultures, in contrast, lack the multicellular organization and dynamic microenvironment necessary to replicate human retinal complexity. Retinal organoids (ROs), three-dimensional tissue constructs derived from pluripotent stem cells, have emerged as a promising model due to their human origin and complex cellular interactions that cannot be achieved in conventional 2-D/3-D co-culture models. In this review, we provide a brief overview of the evolution from 2-D to 3-D retinal models, highlight the structural and functional features of ROs including the presence of layered retinal architecture, photoreceptor outer segment formation, and light-responsive electrophysiological activity and summarize their applications in disease modeling, drug discovery, and gene and cell therapy. ROs represent a significant advancement over traditional models by enabling the recapitulation of human-specific retinal development, facilitating the study of patient-derived disease phenotypes, and providing a platform for personalized therapeutic screening. Their development has deepened understanding of pathological mechanisms in conditions such as retinitis pigmentosa and AMD, while enabling preclinical testing of targeted interventions like CRISPR-based gene editing and photoreceptor cell replacement. Nonetheless, challenges remain in fully replicating retinal vascularization, long-term functional maturation, and synaptic connectivity, underscoring the need for continued refinement and integration with complementary model systems.},
}

@article {pmid42072143,
year = {2026},
author = {Maggi, MA and Mastromartino, R and Piccardi, M and Minnella, AM and Marangoni, D and Di Marco, S and Falsini, B and Bisti, S},
title = {Saffron as a Retinal Neuroprotectant: A Narrative Review of Preclinical Studies and Clinical Results.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
doi = {10.3390/antiox15040501},
pmid = {42072143},
issn = {2076-3921},
abstract = {The present narrative review reports the main preclinical and clinical results obtained by using supplementation of saffron or its pure components in neurodegeneration, with special emphasis on age-related macular degeneration. Beyond that, this article will address shared pathways between neurodegenerative diseases of the eye and the brain. It will be shown that saffron treatment might counteract oxidative damage in the retina and brain, as well as inflammation and inflammatory mediators that induce neuronal degeneration and death. The ways of action are multiple, and saffron chemical components appear to act in a synergistic manner, inducing tissue resilience. These effects critically depend upon the saffron chemical composition and structure. A well-defined ratio among molecules is linked to a patented batch known as Repron[®] and offers the maximum protection against neurodegeneration.},
}

@article {pmid42072148,
year = {2026},
author = {Wiciński, M and Fajkiel-Madajczyk, A and Kurant, Z and Rzepiński, Ł and Słupski, M},
title = {Review of Therapeutic Potential of Coenzyme Q10 in Ophthalmology: Focus on Age-Related Macular Degeneration, Glaucoma, and Retinitis Pigmentosa.},
journal = {Antioxidants (Basel, Switzerland)},
volume = {15},
number = {4},
pages = {},
doi = {10.3390/antiox15040506},
pmid = {42072148},
issn = {2076-3921},
abstract = {Coenzyme Q10 (CoQ10), a natural antioxidant produced by the human body, has strong anti-inflammatory properties, reduces oxidative stress, and improves mitochondrial function. It is also known for its strong neuroprotective effects. With age, endogenously produced CoQ10 levels decline, contributing to the development of chronic diseases, including eye disorders. Irreversible ocular diseases that result in blindness present a significant challenge in contemporary medicine, as no fully effective cure exists; current treatments primarily aim to decelerate disease progression, manage symptoms, and preserve residual vision. Our study reviews research on the use of CoQ10 in eye diseases like age-related macular degeneration (AMD), retinitis pigmentosa (RP), and glaucoma, which can cause permanent vision loss and are linked to oxidative stress and mitochondrial dysfunction. This article explores whether CoQ10 can be a safe and effective addition to treatment for these conditions. We also outline directions for future research and explain how CoQ10 functions in the studies discussed in this review.},
}

@article {pmid42072314,
year = {2026},
author = {Menna, F and De Luca, L and Meduri, A and Baldascino, A and Lupo, S and Vingolo, EM},
title = {New Clinical Trials and Therapeutic Advances with Faricimab and Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration: A Durability-Oriented Comparative Perspective.},
journal = {Biomedicines},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/biomedicines14040773},
pmid = {42072314},
issn = {2227-9059},
abstract = {Neovascular age-related macular degeneration (nAMD) remains a major cause of visual morbidity worldwide, although its contribution to blindness in developed healthcare systems has declined in the era of anti-VEGF therapy. Although randomized clinical trials have consistently demonstrated meaningful visual gains under structured retreatment protocols, real-world outcomes frequently decline over time due to undertreatment, limited durability, and persistent disease activity. Recent therapeutic advances have shifted the focus from maximizing short-term efficacy to engineering sustained disease control. Faricimab, a bispecific antibody targeting both VEGF-A and angiopoietin-2, introduces dual-pathway vascular modulation, while high-dose aflibercept (8 mg) enhances VEGF suppression through pharmacokinetic intensification. This perspective critically examines the biological rationale, clinical evidence, real-world implications, and strategic positioning of these agents, proposing a durability-centered framework for next-generation management of nAMD.},
}

@article {pmid42072323,
year = {2026},
author = {Menna, F and Pinelli, C and De Luca, L and Meduri, A and Baldascino, A and Lupo, S and Vingolo, EM},
title = {From Genetic Diagnosis to Therapeutic Implementation in Retinal Diseases: Translational Advances and Persistent Bottlenecks.},
journal = {Biomedicines},
volume = {14},
number = {4},
pages = {},
doi = {10.3390/biomedicines14040782},
pmid = {42072323},
issn = {2227-9059},
abstract = {Background: Retinal and optic nerve disorders are a leading cause of irreversible visual impairment worldwide. Advances in molecular genetics-including next-generation sequencing, genome-wide association studies, and gene-based therapeutic technologies-have reshaped understanding of both inherited and complex retinal diseases. However, translating genetic discovery into sustained clinical benefit remains biologically and practically constrained. Methods: A structured literature search was conducted using PubMed and Scopus to identify relevant studies published between 2015 and 2025. The search focused on molecular genetics, epigenetic modulation, mitochondrial biology, and translational applications in inherited retinal dystrophies and selected complex retinal diseases, prioritizing high-impact original research and systematic reviews addressing diagnostic innovation and therapeutic development. Results: Inherited retinal dystrophies represent the most advanced model of precision ophthalmology, with diagnostic yields approaching 70-80% in well-characterized cohorts. Gene augmentation and genome-editing strategies have demonstrated proof-of-concept efficacy, yet clinical benefit depends on residual cellular viability, delivery efficiency, and durability of expression. Emerging platforms include AAV-mediated gene transfer, in vivo CRISPR-based editing, RNA-directed splice modulation, and mitochondrial-targeted approaches. Persistent barriers include unresolved non-coding and structural variants, variant interpretation uncertainty, and endpoint selection in clinical trials. In contrast, complex retinal diseases such as glaucoma, age-related macular degeneration, and pathological myopia reflect polygenic susceptibility interacting with environmental and aging-related factors. Although polygenic risk scores refine probabilistic prediction, their utility is limited by ancestry bias and incomplete predictive performance. Epigenetic and mitochondrial mechanisms further modulate disease expression but remain largely non-actionable in routine practice. Conclusions: Retinal genetics has progressed from gene discovery to early therapeutic implementation. Future advances will depend on improved variant detection, functional validation, biomarker-guided staging, and integration of genomics with imaging and longitudinal modeling to achieve durable and equitable precision ophthalmology.},
}

@article {pmid42072770,
year = {2026},
author = {Unlu, BH and Durmaz Engin, C and Ozturk, AT},
title = {The Role of Systemic Inflammation in Age-Related Macular Degeneration Subtypes: Exploring Novel Biomarkers.},
journal = {Diagnostics (Basel, Switzerland)},
volume = {16},
number = {8},
pages = {},
doi = {10.3390/diagnostics16081144},
pmid = {42072770},
issn = {2075-4418},
abstract = {Background/Objectives: This study aimed to compare hematological and inflammatory markers among patients with dry and wet age-related macular degeneration (AMD) and healthy controls, and to evaluate the influence of geographic atrophy (GA) in dry AMD and treatment response (TR) in wet AMD on these markers. Methods: The study included patients with dry AMD (n = 54), wet AMD (n = 53), and age- and sex-matched controls (n = 55). Hematological parameters, serum albumin, and systemic inflammatory indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), and hemoglobin, albumin, lymphocyte, and platelet index (HALP), were compared among the groups. Results: Age and sex distributions did not differ significantly between groups. Compared to controls, the wet AMD group had significantly higher neutrophil counts (p = 0.013), red cell distribution width (RDW) (p = 0.033), and inflammatory indices, including NLR, PLR, SII, SIRI, and PIV (all p < 0.01). HALP levels were significantly lower in wet AMD (p < 0.001). Dry AMD patients also had higher PLR (p = 0.045) and RDW (p = 0.005) than controls. When comparing wet and dry AMD groups directly, SIRI (p = 0.041) and PIV (p = 0.029) were significantly elevated in wet AMD, indicating stronger systemic inflammatory burden. In the dry AMD subgroup, patients with GA had significantly lower hemoglobin (p = 0.002) and erythrocyte counts (p = 0.039) than those without GA. No significant differences were observed between TR-positive and TR-negative wet AMD patients. Conclusions: Patients with wet AMD exhibit a more pronounced systemic inflammatory profile than both dry AMD patients and healthy controls. These findings support the hypothesis that systemic inflammation may contribute to AMD pathogenesis. Geographic atrophy in dry AMD may also be associated with additional hematologic alterations, whereas treatment response in wet AMD is not reflected in systemic markers.},
}

@article {pmid42074336,
year = {2026},
author = {Bruzaite, A and Vilkeviciute-Petraite, A and Cebatoriene, D and Zaliuniene, D and Ciapiene, I and Smalinskiene, A and Kriauciuniene, L and Liutkeviciene, R},
title = {Metabolic and Genetic Alterations in Early and Exudative Age-Related Macular Degeneration: Inosine, Amino Acids, and COL2A1 Gene Variant.},
journal = {International journal of molecular sciences},
volume = {27},
number = {8},
pages = {},
doi = {10.3390/ijms27083697},
pmid = {42074336},
issn = {1422-0067},
support = {S-MIP-23-96//Research Council of Lithuania/ ; },
mesh = {Humans ; Female ; Male ; Aged ; *Polymorphism, Single Nucleotide ; *Macular Degeneration/genetics/metabolism ; *Inosine/metabolism ; *Amino Acids/metabolism ; *Collagen Type II/genetics/metabolism ; Genetic Predisposition to Disease ; Middle Aged ; Genotype ; Case-Control Studies ; Alleles ; Aged, 80 and over ; },
abstract = {Age-related macular degeneration (AMD) is a complex retinal disease influenced by genetic and metabolic factors. Genetic variants impact disease susceptibility, while alterations in amino acid and purine metabolism are involved in AMD development. This study aimed to examine the association between the COL2A1 rs1635529 polymorphism and AMD, as well as its relation to specific metabolites. The study comprised 919 participants: 261 with early AMD, 229 with exudative AMD, and 429 controls. DNA was extracted using the salting-out method, and genotyping was performed using real-time PCR. Metabolite levels were analysed with liquid chromatography-mass spectrometry. Statistical analysis was conducted using IBM SPSS Statistics 27.0. Logistic regression revealed that carriers of the GT + TT genotypes had a 1.63-fold higher risk of early AMD (p = 0.046). The T allele was also linked to a 1.67-fold elevated risk (p = 0.033). No significant associations were observed in exudative AMD. Furthermore, lower leucine levels were noted in exudative AMD patients, and inosine levels were reduced in GT genotype carriers within the early AMD group. The COL2A1 rs1635529 polymorphism showed a nominal association with early AMD, but not exudative AMD. Differences in leucine and inosine levels were observed, suggesting a potential link between genetic variation and metabolic alterations. These findings indicate possible involvement of collagen-related and metabolic pathways in early disease development; however, the results should be interpreted with caution and require validation in larger studies.},
}

Humans
Female
Male
Aged
*Polymorphism, Single Nucleotide
*Macular Degeneration/genetics/metabolism
*Inosine/metabolism
*Amino Acids/metabolism
*Collagen Type II/genetics/metabolism
Genetic Predisposition to Disease
Middle Aged
Genotype
Case-Control Studies
Alleles
Aged, 80 and over

@article {pmid42074510,
year = {2026},
author = {Rowe, LW and Becerra, SP and MacLaren, RE and Avery, RL and Wykoff, CC and Ho, AC and Regillo, CD and Eliott, D and Osborne, A and Binley, KM and Ciulla, TA},
title = {Gene-Agnostic Therapeutic Strategies for Inherited Retinal Diseases: Neuroprotection and Immunomodulation.},
journal = {Genes},
volume = {17},
number = {4},
pages = {},
doi = {10.3390/genes17040392},
pmid = {42074510},
issn = {2073-4425},
mesh = {Humans ; *Genetic Therapy/methods ; *Retinal Diseases/genetics/therapy ; *Neuroprotection/genetics ; *Immunomodulation/genetics ; Animals ; Nerve Growth Factors/genetics ; },
abstract = {Background/Objectives: Inherited retinal diseases (IRDs) represent a genetically heterogeneous group of disorders caused by mutations in over 280 genes with more than 3100 identified variants. While gene-specific replacement therapies have achieved landmark success with voretigene neparvovec (Luxturna) for biallelic RPE65-associated retinal dystrophy, developing individual therapies for each genetic subtype remains impractical. This review examines gene-agnostic therapeutic approaches utilizing neuroprotection and immunomodulation that target common pathophysiological mechanisms shared across multiple IRD genotypes. Methods: We reviewed the literature on neuroprotective and immunomodulatory gene therapy strategies for IRDs, focusing on neurotrophic factors and complement system modulation. Results: Neuroprotective approaches delivering neurotrophic factors-including pigment epithelium-derived factor (PEDF), ciliary neurotrophic factor (CNTF), rod-derived cone viability factor (RdCVF), brain-derived neurotrophic factor (BDNF), fibroblast growth factors (FGFs), glial cell line-derived neurotrophic factor (GDNF), and proinsulin-have demonstrated photoreceptor preservation across multiple preclinical IRD models regardless of the underlying genetic mutation. The recent FDA approval of CNTF cell-based gene therapy (Encelto) for macular telangiectasia type 2 validates this therapeutic paradigm. Complement system inhibition represents another gene-agnostic strategy, with intravitreal complement inhibitors approved for geographic atrophy secondary to age-related macular degeneration and gene therapy approaches targeting C3, C5, or delivering soluble complement regulators under investigation for IRDs. Combination strategies simultaneously addressing multiple pathogenic pathways may offer synergistic benefits. Conclusions: Gene-agnostic approaches targeting neuroprotection and immunomodulation offer a therapeutic paradigm capable of benefiting patients across the spectrum of IRD genotypes, potentially transforming treatment for conditions where mutation-specific therapies remain unavailable.},
}

Humans
*Genetic Therapy/methods
*Retinal Diseases/genetics/therapy
*Neuroprotection/genetics
*Immunomodulation/genetics
Animals
Nerve Growth Factors/genetics

@article {pmid42074639,
year = {2026},
author = {Kamao, H and Goto, K and Mizukawa, K and Hiraki, R and Miki, A and Kimura, S},
title = {Five-Year Changes in Pachydrusen with Late-Phase Hyperfluorescence on Indocyanine Green Angiography.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082836},
pmid = {42074639},
issn = {2077-0383},
abstract = {Background/Objectives: Pachydrusen are a drusen subtype associated with the pachychoroid disease spectrum; however, their long-term natural history and pathophysiological significance remain unclear. We investigated 5-year morphological and topographic changes in pachydrusen using diagnostic criteria incorporating late-phase indocyanine green angiography (ICGA) hyperfluorescence. Methods: This retrospective observational study included fellow eyes with pachydrusen from patients with unilateral neovascular age-related macular degeneration. Pachydrusen were defined as sub-retinal pigment epithelium (RPE) deposits ≥ 125 µm in size with corresponding hyperfluorescence on late-phase ICGA. Lesion number, size, and spatial distribution (ETDRS grid and quadrant-based classification) were evaluated at baseline and 5 years. The incidence of macular neovascularization (MNV) and its colocalization with pachydrusen were assessed. Results: Among 57 fellow eyes with pachydrusen, incident MNV developed in 8 eyes (14.0%) during follow-up; the mean time to onset was 25.6 ± 16.3 months. No clear colocalization between pachydrusen and incident MNV was observed. Nineteen eyes completed the 5-year follow-up period. Pachydrusen were predominantly located outside the 6000 µm ETDRS grid at baseline (63.4%) and 5 years (66.3%), significantly exceeding the expected proportion based on the area ratio (p < 0.001). The lesions were most frequently observed in the superotemporal quadrant (52.6%). Over 5 years, 19.8% of the lesions increased in size, 67.2% remained stable, and 12.9% regressed; none of the regressed lesions were accompanied by RPE atrophy. Conclusions: Pachydrusen, defined as late-phase ICGA hyperfluorescence, was predominantly distributed outside the ETDRS grid with a superotemporal predilection and could increase or decrease over a 5-year follow-up period. No colocalization with MNV was observed, and no accompanying RPE atrophy after pachydrusen regression was identified, suggesting that late-phase ICGA-hyperfluorescent pachydrusen may represent a pathophysiology distinct from that of soft drusen.},
}

@article {pmid42074670,
year = {2026},
author = {Sanders, FWB and Acton, JH and Ryan, B and McAlinden, C},
title = {Psychometric Assessment of the Metamorphopsia Questionnaire in Patients with Macular Diseases Receiving Anti-Vascular Endothelial Growth Factor Treatment.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082867},
pmid = {42074670},
issn = {2077-0383},
support = {2023/2024(ER)-ER-23-07-Dr Francis William Barwise Sanders//HCRW/ ; },
abstract = {Background: The metamorphopsia questionnaire (MeMoQ) is an established patient-reported outcome measure (PROM) in the context of macular disease. However, its performance has not been proved in those being treated for various macular conditions with intravitreal anti-vascular endothelial growth factor (Anti-VEGF). The objective was to eliminate misfitting items, enhance measurement precision, and ensure optimal response categorisation. Methods: Rasch analysis was performed iteratively on 2286 responses from patients with macular diseases being treated with Anti-VEGF to optimise the MeMoQ. Fit statistics, reliability indices, person and item separation measures, and principal component analysis (PCA) of residuals were assessed to determine the optimal model. This study was conducted in an outpatient clinic specialising in retinal diseases in Hywel Dda University Health Board. Results: Misfitting items were removed in successive iterations, leading to optimised category probability curves and stable fit statistics for the MeMoQ. The resulting model for all responses included two final items, with person separation remaining inadequate reducing from 1.23 to 1.12 and reliability from 0.60 to 0.56. Category probability curves demonstrated good ordering of response variables with Andrich thresholds separated by >1.2 logits. In the subgroups of neovascular age-related macular degeneration and diabetic macular oedema person separation remained below two and reliability remained low. Conclusions: Rasch analysis demonstrated that the MeMoQ was not a valid or reliable PROM in this patient population. Therefore, the MeMoQ may not provide a reliable index of patient's perception and visual experience when undergoing Anti-VEGF treatment.},
}

@article {pmid42074763,
year = {2026},
author = {Dmoch, W and Sawicka, J and Żelichowska, N and Kępczyńska, Z and Maciejewicz, P and Kęcik, D},
title = {Statins and Fibrates in Age-Related Macular Degeneration: A Contemporary Clinical Narrative Review (2020-2025).},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082960},
pmid = {42074763},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) remains the leading cause of irreversible central vision loss in the elderly. Increasing attention has been directed toward lipid metabolism as a potential contributor to disease onset and progression. The overlap between AMD and atherosclerosis-particularly regarding lipid accumulation, endothelial dysfunction, and chronic inflammation-has prompted interest in lipid-lowering therapies. This narrative review synthesizes the clinical evidence published between 2020 and 2025 on the potential role of statins and fenofibrate in AMD risk modification and disease progression. A structured literature search was conducted in PubMed, Scopus, and Web of Science using combined MeSH and free-text terms related to lipid-lowering agents and AMD. Human studies evaluating clinical incidence or progression outcomes were considered alongside contextual evidence from prior evidence syntheses. Overall, findings remain heterogeneous. Most studies did not demonstrate a consistent association between statin therapy and AMD incidence or progression in unselected populations. However, selected reports suggested a potential delay in dry AMD onset or slower disease progression among patients receiving prolonged or higher-intensity statin treatment. Evidence regarding fenofibrate was more limited and heterogeneous, with only a tentative protective signal observed in adherent users, particularly for non-exudative AMD. The current literature does not support lipid-lowering therapy as a universal preventive strategy for AMD. Nonetheless, subgroup-specific benefits cannot be excluded, especially in early disease stages or metabolically high-risk populations. Further well-designed prospective and randomized studies are needed to clarify therapeutic relevance and identify the patients who are most likely to benefit.},
}

@article {pmid42074798,
year = {2026},
author = {Nagano, N and Kanemori, E and Hirano, Y and Hojo, T and Sakaeda, Y and Yuguchi, T and Kuwayama, S and Ogura, S and Kimura, M and Morita, H and Uemura, K and Yasukawa, T},
title = {Assessing the Validity of the Fellow Eye as an Internal Control in Early-Phase Clinical Trials for Myopic Chorioretinal Atrophy.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15082997},
pmid = {42074798},
issn = {2077-0383},
support = {Not applicable//PharmaBio Corporation/ ; },
abstract = {Background/Objectives: Age-related macular degeneration, particularly geographic atrophy, is a major cause of irreversible vision loss and shares pathological features with myopic chorioretinal atrophy (CRA). This study was designed as an exploratory methodological analysis to evaluate the feasibility of using the fellow eye as an internal control in early-phase clinical trials for myopic CRA. Methods: This exploratory and methodological retrospective study included eight patients (16 eyes) with myopic CRA who visited the Department of Ophthalmology at Nagoya City University Hospital between January 2010 and August 2023. Atrophic areas in both eyes were measured, and the longitudinal changes were analyzed. Three mixed-effects models were compared to assess the impact of inter-individual and inter-ocular variability on atrophic area progression. Subsequently, fixed-effects and mixed-effects models were compared using the Akaike Information Criterion (AIC). Finally, the square root of the variance ratio was calculated to quantify the contribution of inter-ocular variability to atrophic area progression. Results: In all eyes, the square root of the atrophic area increased over time. The model including random intercepts and slopes for each eye nested within patients had the lowest AIC of 69.4, suggesting that accounting for both inter-individual and inter-ocular variability improved model accuracy. The mixed-effects model had a lower AIC than the fixed-effects model, indicating a better fit. The square root of the variance ratio was 0.34 in the mixed-effects model, indicating that the inter-ocular variability was lower than the inter-individual variability, though it remained appreciable. Conclusions: This study quantitatively supports the feasibility and methodological validity of inter-ocular comparison designs for early-phase clinical trials in myopic CRA.},
}

@article {pmid42074899,
year = {2026},
author = {Ahmad, NU and Mir, TA},
title = {Advances in Gene Therapy for Age-Related Macular Degeneration: A Narrative Review.},
journal = {Journal of clinical medicine},
volume = {15},
number = {8},
pages = {},
doi = {10.3390/jcm15083097},
pmid = {42074899},
issn = {2077-0383},
abstract = {Age-related macular degeneration (AMD) is the most common cause of blindness and vision impairment in individuals over 60 years of age in the United States (US). Despite this, current treatment options have limitations related to drug efficacy and durability. Gene therapy provides a potential solution by providing a more durable and longer- acting treatment option that can decrease treatment burden and improve long-term visual outcomes. This review presents the current treatment approaches, routes of administration, and vectors being investigated for gene therapy delivery in AMD. It also provides an update on the ongoing gene therapy clinical trials for dry and wet AMD. As these therapies advance into later-stage clinical trials, ophthalmologists need to be mindful of the many challenges pertaining to gene therapy delivery, including safety, limitations related to immunogenicity, long-term ocular and systemic side effects, and potential barriers to drug manufacturing and access. Continued efforts are required to improve precision, safety, and efficacy, including identifying the safest and most effective vectors and delivery routes, and minimizing potential adverse effects. In addition, guidelines need to be established to guide appropriate patient selection before gene therapy can be integrated into clinical practice.},
}

@article {pmid42079735,
year = {2026},
author = {Yu, B and Liu, L and Yang, N and Xu, L and Wu, H},
title = {Visual acuity and stereopsis across the parafoveal and perifoveal retina in young adults: an eccentricity and meridian analysis.},
journal = {PeerJ},
volume = {14},
number = {},
pages = {e21251},
pmid = {42079735},
issn = {2167-8359},
mesh = {Humans ; *Visual Acuity/physiology ; Male ; Female ; Adult ; *Depth Perception/physiology ; Young Adult ; *Retina/physiology ; *Fovea Centralis/physiology ; Vision, Binocular/physiology ; },
abstract = {BACKGROUND: Visual acuity (VA) and stereoacuity (SVA) are fundamental visual functions that decline with increasing retinal eccentricity. Patients with macular degeneration and other central vision disorders often rely on paracentral vision, yet location-specific reference data for VA and SVA across the parafoveal and perifoveal retina remain limited. This study aimed to quantify the distribution of binocular VA and SVA across eccentricity and meridian in young adults, develop prediction equations with 95% prediction intervals, and examine the relationship between these two visual functions in the paracentral retina.

METHODS: Thirty-five healthy young adults (13 males, 22 females; mean age 27.23 ± 2.43 years) were recruited. Binocular VA and SVA were measured at 48 test positions across eight meridians (0°, 45°, 90°, 135°, 180°, 225°, 270°, 315°) and six eccentricities (2.5° to 15° in 2.5° increments) using a polarized 3D display system. A four-alternative forced-choice task was employed with tumbling E optotypes for VA and random-dot stereograms for SVA. Eye tracking ensured fixation stability throughout testing. Generalized estimating equations were used to analyze the effects of eccentricity and meridian. Linear mixed-effects models and Bayesian Tobit models were employed to develop prediction equations. Ten-fold cross-validation assessed model generalizability.

RESULTS: Both VA and SVA significantly declined with increasing eccentricity (P < 0.001). VA decreased from a median of 0.40 logMAR at 2.5° to 1.20 logMAR at 15.0°, at a rate of 0.057 logMAR per degree. SVA increased from 2.1 log arcsec at 2.5° to 2.9 log arcsec at 7.5°, declining approximately three times faster than VA (0.154 log arcsec per degree). Both functions showed significant meridional anisotropy (P < 0.001), with the horizontal meridian demonstrating 0.058 logMAR better VA and 0.106 log arcsec better SVA compared to the vertical meridian. Despite parallel declines with eccentricity, no significant correlations were observed between VA and SVA at any test position within 7.5° eccentricity (P > 0.05).

CONCLUSIONS: VA and SVA deteriorate with increasing eccentricity in the paracentral retina, with stereopsis declining approximately three times faster and demonstrating a more pronounced horizontal-over-vertical advantage. The absence of correlation between VA and SVA suggests distinct neural mechanisms underlying these functions. The prediction equations with 95% prediction intervals provide reference benchmarks for healthy young adults, facilitating clinical interpretation of patient measurements and enabling objective assessment of disease-related changes in paracentral visual function.},
}

Humans
*Visual Acuity/physiology
Male
Female
Adult
*Depth Perception/physiology
Young Adult
*Retina/physiology
*Fovea Centralis/physiology
Vision, Binocular/physiology

@article {pmid42079755,
year = {2026},
author = {Zhu, S and Yang, T and Sheng, L and Shi, L},
title = {TREM2 in age-related macular degeneration: a microglia-centered perspective in the retinal myeloid landscape.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1804578},
pmid = {42079755},
issn = {2674-0826},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults. Advanced AMD comprises an atrophic ("dry") form characterized by retinal pigment epithelium (RPE) and photoreceptor degeneration and a neovascular ("wet") form driven by choroidal neovascularization (CNV). Beyond genetic predisposition and environmental stressors, chronic dysregulation of innate immunity is increasingly recognized as a convergent mechanism linking drusen/Bruch's membrane alterations to outer retinal cell death and pathological angiogenesis. Retinal myeloid cells-including resident microglia and, in specific disease contexts, recruited monocyte-derived macrophages-can support homeostasis by clearing lipids and cellular debris, yet may also exacerbate inflammation, matrix remodeling, and neovascularization. Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed by microglia and other myeloid cells that regulates phagocytosis, lipid handling, migration, survival, immunometabolism, and inflammatory tone. Recent retinal studies suggest that TREM2-associated programs can restrain lesion expansion in outer retinal degeneration models and modulate CNV severity in experimental neovascularization; however, interpretation remains limited by disease stage, anatomical niche, and the difficulty of cleanly separating microglia from infiltrating macrophages in vivo. Here, we synthesize current evidence on retinal myeloid contributions to dry and neovascular AMD, provide an updated mechanistic framework for TREM2 signaling, and discuss therapeutic strategies and translational challenges for targeting TREM2 in AMD.},
}

@article {pmid42080790,
year = {2026},
author = {Piroozmand, S and Latifi-Navid, H and Soheili, ZS and Hosseinkhani, S and Samiei, S and Barzegar Behrooz, A and Ahmadieh, H and Leonardi, A and Ghavami, S and Sheibani, N},
title = {Suboptimal Responses to Anti-VEGF in Retinal Neurovascular Diseases: Linking Aging and Alternative Angioinflammatory Pathways.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {4},
doi = {10.1167/iovs.67.5.4},
pmid = {42080790},
issn = {1552-5783},
mesh = {Humans ; *Angiogenesis Inhibitors/therapeutic use ; *Vascular Endothelial Growth Factor A/antagonists & inhibitors ; *Aging/physiology ; Signal Transduction ; *Retinal Diseases/drug therapy/metabolism ; },
abstract = {PURPOSE: Vision-threatening ocular diseases are impacted by aging-associated molecular changes, including mitochondrial dysfunction, cellular senescence, and chronic inflammation. Anti-VEGF therapies targeting VEGF-A/VEGFR2 signaling remain the frontline standard of care, but many patients exhibit suboptimal or nondurable responses, often due to compensatory and/or compromised antiangiogenic and anti-inflammatory pathways. We aimed to elucidate shared mechanisms underlying treatment failure and disease progression.

METHODS: We applied an integrative systems biology framework that combined multiomics datasets, network-based machine learning, and disease-specific pathway mapping. A comprehensive literature review of conditions, including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and aging, identified 14 core genes consistently associated with angiogenesis, inflammation, and immune signaling. Multialgorithm centrality and enrichment analyses reconstructed disease-specific interaction networks, revealing consensus mechanistic axes. Integration of cell-type-specific single-cell RNA sequencing data from AMD-RPE clusters identified cluster-specific gene hubs and vertical signaling axes, leading to VEGF blockade failure.

RESULTS: EGFR, HSP90AA1, SIRT1, and STAT3 emerged as central resistance hubs linking angiogenesis and inflammatory processes. Pathway enrichment analyses revealed 21 conserved core signaling cascades, grouped into six functional categories, with AGE-RAGE, PI3K-Akt, HIF-1, MAPK, and chemokine pathways playing central roles. A MiRGD-based peptide nanocomplex delivering htsFLT01 achieved efficient RPE transfection and controlled gene activation under basal conditions.

CONCLUSIONS: This systems-level framework clarifies mechanisms of VEGF blockade resistance and provides a rational basis for next-generation, combinatorial therapeutic strategies requiring validation in disease-relevant models.},
}

Humans
*Angiogenesis Inhibitors/therapeutic use
*Vascular Endothelial Growth Factor A/antagonists & inhibitors
*Aging/physiology
Signal Transduction
*Retinal Diseases/drug therapy/metabolism

@article {pmid42080917,
year = {2026},
author = {Haroon, MM and Akram, L and Jalal, L and Ahmed, A and Haider, S},
title = {Granzyme B in age-related macular degeneration: mechanistic insights and therapeutic perspectives.},
journal = {Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie},
volume = {},
number = {},
pages = {},
pmid = {42080917},
issn = {1435-702X},
abstract = {Granzyme B (GzmB), beyond its established role in corneal and conjunctival disease, is increasingly recognized in the retinal and choroidal distribution of several pathologies. GzmB targets tight-junction proteins (e.g., ZO-1, JAM-A) and extracellular proteins such as fibronectin and laminin within the retinal pigment epithelium (RPE) and Bruch's membrane, thereby disrupting the outer blood-retinal barrier and contributing to the pathogenesis of age-related macular degeneration (AMD) and Macular neovascularization (MNV). This mini review highlights recent mechanistic insights into how GzmB drives extracellular matrix breakdown, inflammation, and angiogenesis; summarizes experimental and clinical evidence supporting its role in AMD; and discusses emerging therapeutic approaches, limitations, and translational potential for targeted therapy.},
}

@article {pmid42081160,
year = {2026},
author = {Lin, Y and Han, Z and Zhang, Y and Yuan, R and Huang, M and Liu, Y and Wang, J and Xu, C and Liu, L and Yu, P and Yang, Q and Zeng, L and Li, S},
title = {The aging eye: navigating molecular mechanisms and innovative interventions.},
journal = {Biogerontology},
volume = {27},
number = {3},
pages = {},
pmid = {42081160},
issn = {1573-6768},
mesh = {Humans ; *Aging/pathology/metabolism ; Oxidative Stress ; Animals ; Cellular Senescence ; *Eye/metabolism/pathology ; *Eye Diseases/therapy/metabolism ; Autophagy ; },
abstract = {The global demographic shift toward aging has precipitated a surge in age-related ocular pathologies, imposing a formidable public health challenge that demands urgent intervention. Blinding disorders such as age-related macular degeneration (AMD), cataracts, and dry eye disease exemplify this crisis, with their pathogenesis being intrinsically linked to tissue-specific aging processes in the eye. At the molecular level, core pathways including telomere attrition, oxidative stress, cellular senescence, and autophagic dysregulation orchestrate this degenerative cascade. This review systematically delineates the dynamic interplay network of these pathways during ocular aging, with particular emphasis on four pivotal mechanisms: oxidative stress-driven reactive oxygen species (ROS) accumulation, senescence-associated secretory phenotype (SASP)-mediated inflammatory cascades, autophagic flux dysfunction, and epigenetic remodeling aberrations. We further evaluate recent advancements in translational therapies, emphasizing the clinical potential of targeted gene-editing technologies, stem cell-derived regenerative approaches, and novel senolytic agents. Additionally, artificial intelligence (AI) -assisted diagnostics are explored as pivotal tools for precision medicine, particularly in early disease detection via retinal imaging and biomarker analysis. Future research priorities should focus on the integration of aging-specific biomarkers including methylation signatures, the advancement of tissue-selective drug delivery systems tailored to anterior and posterior ocular compartments. Collectively, these initiatives will propel the development of targeted interventions to address age-related visual decline, positioning precision medicine as the cornerstone of next-generation geriatric ophthalmic care.},
}

Humans
*Aging/pathology/metabolism
Oxidative Stress
Animals
Cellular Senescence
*Eye/metabolism/pathology
*Eye Diseases/therapy/metabolism
Autophagy

@article {pmid42081293,
year = {2026},
author = {Procyk, CA and Melati, A and Tariq, M and Liu, J and Branch, MJ and Delicata, JD and Harding, P and Khazim, M and Moshtagh Khorasani, M and Ladino, B and Lanning, EP and Margari, M and Mahamoud, I and Mofidi, C and Kumar, KN and Van Heerden, S and Smith, AJ and West, EL and Ali, RR and Pearson, RA},
title = {Transplantation of human stem cell-derived cone photoreceptors partially restores vision in aged rd1 mice with advanced retinal degeneration.},
journal = {Stem cells (Dayton, Ohio)},
volume = {},
number = {},
pages = {},
doi = {10.1093/stmcls/sxag023},
pmid = {42081293},
issn = {1549-4918},
abstract = {Targeted photoreceptor replacement therapy is a promising, potentially disease-agnostic approach for reversing sight-loss associated with advanced retinal degenerations, including age-related macular degeneration. We have previously shown that transplantation of human stem cell-derived cone photoreceptors (hCones) into young adult (3-month-old) mouse models of advanced retinal degeneration can restore retinal function. However, substantial remodeling of the remaining inner retinal circuitry continues long after complete photoreceptor loss, raising the critical question of whether photoreceptor transplantation can effectively rescue function at very late-stage degeneration. rd1 mice received transplants at 12-15 months of age and were examined ∼3 months later. Transplanted hCones survived in large numbers, while host inner retinal neurons exhibited significant plasticity, extending dendrites to transplanted hCones, and making synapse-like contacts. Host Müller glia undergo notable remodeling, apparently incorporating the donor cells within the retinal structure. Multielectrode array recordings showed robust rescue of light-evoked activity across the normal photopic range intensities and evidence of inner retinal processing, while some treated mice showed improvements in visually-evoked optokinetic head tracking behavior. Together, these data indicate that effective rescue following photoreceptor replacement therapy is feasible long after complete photoreceptor loss and extensive inner retinal remodeling.},
}

@article {pmid42082070,
year = {2026},
author = {Tran, J and Chhablani, J},
title = {Unsuccessful Clinical Trials in Retina: Lessons Learned.},
journal = {American journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.ajo.2026.04.028},
pmid = {42082070},
issn = {1879-1891},
abstract = {OBJECTIVE: To analyze patterns of non-success in phase 2 and 3 interventional retinal clinical trials conducted in the United States between 2015 and 2025.

DESIGN: Perspective based on retrospective analysis of unsuccessful clinical trials.

METHODS: Unsuccessful trials that were terminated, withdrawn, or completed without meeting primary endpoints were evaluated across indications, trial phases, intervention classes, and mechanisms of action to identify recurring design, feasibility, and operational challenges.

RESULTS: High attrition rates were observed across diabetic macular edema, diabetic retinopathy, neovascular age-related macular degeneration, and geographic atrophy. Phase 2 trials were more frequently discontinued following interim analyses, whereas phase 3 trials more often failed to meet primary efficacy endpoints. Later-phase studies were associated with increased sample size, geographic dispersion, follow-up duration, and assessment burden. Differences in endpoint selection, comparator choice, and population heterogeneity may contribute to attenuation of treatment effects. Operational and sponsor-level factors, including strategic and financial considerations, were also associated with trial discontinuation.

CONCLUSION: Translating early-stage findings into successful late-phase outcomes remains challenging in retinal drug development. Improved alignment of biological rationale, endpoint selection, and operational feasibility may enhance trial success.},
}

@article {pmid42082131,
year = {2026},
author = {Duo, L and Cheng, P and Jiang, W and Lin, Q},
title = {Free-standing chondroitin sulfate/collagen multilayered films as preliminary Bruch's membrane-mimetic platform for retinal pigment epithelial cell culture.},
journal = {International journal of biological macromolecules},
volume = {},
number = {},
pages = {152359},
doi = {10.1016/j.ijbiomac.2026.152359},
pmid = {42082131},
issn = {1879-0003},
abstract = {Age-related macular degeneration (AMD) is a leading cause of irreversible blindness, primarily associated with retinal pigment epithelial (RPE) cell degeneration. Although RPE cell therapy has emerged as a promising strategy for AMD, maintaining RPE cell attachment, organization, and functional characteristics remains a major challenge. In this study, free-standing chondroitin sulfate (CS)/collagen (Col) multilayered films were fabricated via spin-coating-assisted layer-by-layer (LbL) assembly and evaluated in vitro as preliminary Bruch's membrane (BM)-mimetic platform for supporting RPE growth and preserving cellular functionality. Genipin cross-linking improved the mechanical stability of the films and reduced their swelling behavior. ARPE-19 cells cultured on the 2 h cross-linked films showed improved attachment and proliferation compared with uncross-linked films, together with detectable RPE65 expression and several RPE-related functional features, including apical-basal differences in pigment epithelium-derived factor (PEDF) secretion, phagocytosis of labeled photoreceptor outer segments (POS), and formation of microvilli-like structures. Collectively, these findings suggest that CS/Col free-standing films can support ARPE-19 cell growth and maintain several RPE-related phenotypic and functional features in vitro, providing a preliminary BM-mimetic platform for future RPE culture studies.},
}

@article {pmid42082322,
year = {2026},
author = {Kortuem, KU and Zarranz-Ventura, J and Bandello, F and Duval, R and O'Toole, L and De Zanet, S and Blair, JPM and Seaman, J and Zvolanek, M and Jaeger, K and Gmeiner, B and Holz, FG},
title = {Impact of AI-enhanced three-dimensional OCT scans on disease activity assessment in patients with nAMD: the RAZORBILL study.},
journal = {The British journal of ophthalmology},
volume = {},
number = {},
pages = {},
doi = {10.1136/bjo-2024-327060},
pmid = {42082322},
issn = {1468-2079},
abstract = {BACKGROUND: The standard of care for neovascular age-related macular degeneration (nAMD) is repeated intravitreal injection with anti-vascular endothelial growth factor agents. Real world evidence suggests that some patients are undertreated, which might be linked with the retreatment decisions made by physicians. Therefore, this multicentre observational study aimed to investigate the extent to which enrichment of optical coherence tomography (OCT) images with segmentation information could influence and support disease activity assessment (DAA) in patients treated for nAMD.

METHODS: Descriptive statistics were tabulated for the demographic and clinical characteristics and outcome variables. To assess the influence of automated OCT image enrichment with segmentation information on DAA, a generalised linear mixed model was employed. The degree of agreement in classification of disease activity across reviewers was assessed by Krippendorff's alpha.

RESULTS: The odds estimate for DAA regarding enriched OCT images was 0.759 and for non-enriched OCT images 0.772. The OR for enriched versus non-enriched OCT images was 1.078 with a p value of 0.229. No difference in the odds of DAA between automated OCT image enrichment with segmentation and DAA was noted. Krippendorff's alpha coefficient was 0.416 for enriched and 0.402 for non-enriched OCT images. Thus, the inter-reviewer reliability/agreement was similarly low between enriched and non-enriched OCT images.

CONCLUSIONS: OCT image enrichment did not appear to impact the likelihood of adequately detecting disease activity, nor did it have an impact on agreement between reviewers of images in this study. No new safety signals in products involved in the study were detected.

TRIAL REGISTRATION NUMBER: NCT04662944.},
}

@article {pmid42066985,
year = {2026},
author = {Cui, X and Zhao, Q and Yuan, J and Yu-Wai-Man, P},
title = {Integrated plasma proteomics and metabolomics reveal immunometabolic pathways and predictive signatures for age-related eye diseases.},
journal = {Metabolism: clinical and experimental},
volume = {180},
number = {},
pages = {156624},
doi = {10.1016/j.metabol.2026.156624},
pmid = {42066985},
issn = {1532-8600},
abstract = {BACKGROUND AND AIMS: Age-related eye diseases (AREDs) share aging as a major risk factor, but the systemic molecular changes preceding disease onset remain incompletely understood. We aimed to define the shared and disease-specific immunometabolic architecture of major AREDs and to examine how circulating molecular features relate to retinal phenotypes, pre-diagnostic patterns, and disease risk.

METHODS: We performed a large-scale prospective multi-omics study in the UK Biobank integrating baseline plasma proteomics, metabolomics, retinal imaging-derived phenotypes, and longitudinal follow-up across five major AREDs: age-related macular degeneration, cataract, diabetic retinopathy, glaucoma, and retinal vascular occlusion. Cox regression, functional enrichment, protein-metabolite correlation, mediation analysis, trajectory analysis, and machine-learning models were applied.

RESULTS: Proteome-wide analyses identified both shared and disease-specific circulating signatures, mainly involving immune, extracellular matrix, vascular, and stress-response pathways. Reconstructed population-level molecular patterns diverged from controls up to 15 years before diagnosis, with marked heterogeneity across diseases. Integration with retinal imaging linked immune- and matrix-related proteins to retinal neurodegenerative and microvascular phenotypes. Metabolite clustering and mediation analyses highlighted recurrent lipoprotein-related pathways, particularly HDL-related structure and composition, as cross-layer features associated with systemic protein signals, metabolic states, and disease risk. Combined proteomic-metabolomic models improved prediction of incident disease compared with protein-only models.

CONCLUSIONS: Major AREDs share a systemic immunometabolic aging architecture while retaining substantial disease-specific molecular features. Circulating molecular alterations are detectable years before clinical onset and may support future biological stratification and risk prediction.},
}

@article {pmid42067026,
year = {2026},
author = {González Escobar, AB and Baquero Aranda, IM and Valera Ávila, JC and Barco Moreno, E and Galván Cano, JM and Luque Aranda, R},
title = {Bilateral peripheral exudative hemorrhagic chorioretinopathy treated with intravitreal injections of ranibizumab.},
journal = {Archivos de la Sociedad Espanola de Oftalmologia},
volume = {},
number = {},
pages = {502539},
doi = {10.1016/j.oftale.2026.502539},
pmid = {42067026},
issn = {2173-5794},
abstract = {Peripheral exudative hemorrhagic chorioretinopathy (PEHCR) is a rare entity consisting of lesions similar to those of age-related macular degeneration (AMD) and type 1 aneurysmal neovascularization (N1a), but located outside the macular region in the peripheral retina. We present the case of an 89-year-old woman who presented to the emergency department with loss of visual acuity (VA) in both eyes (OU) due to a massive macular subretinal hemorrhage in the right eye (OD) and a vitreous hemorrhage in her left eye (OS), accompanied in both eyes by peripheral hemorrhagic retinal pigment epithelium detachments (HPED). Ophthalmological examination and multimodal imaging led to the diagnosis of PEHCR. This case highlights the importance of the differential diagnosis of PEHCR from other vascular and neoplastic pathologies in order to avoid unnecessary tests and treatments. Early recognition and diagnosis are essential for establishing appropriate management, with intravitreal injections of anti-vascular endotelial groth factors (anti-VEGF) being recommended in cases with loss of VA or threat thereof. This case also contributes to the limited published literature on bilateral PEHCR, reinforcing the need to consider this pathology in elderly patients with peripheral hemorrhagic lesions.},
}

@article {pmid42068401,
year = {2026},
author = {Kaplan, E and Segal, O and Moisseiev, E and Allon, G},
title = {Switch to faricimab in various retinal diseases: real-world data.},
journal = {International ophthalmology},
volume = {46},
number = {1},
pages = {},
pmid = {42068401},
issn = {1573-2630},
mesh = {Humans ; Male ; Female ; Intravitreal Injections ; *Retinal Diseases/drug therapy/diagnosis ; Aged ; Retrospective Studies ; *Visual Acuity ; Middle Aged ; Angiogenesis Inhibitors/administration & dosage ; Tomography, Optical Coherence ; Treatment Outcome ; Fluorescein Angiography ; *Drug Substitution ; Aged, 80 and over ; Fundus Oculi ; Follow-Up Studies ; Antibodies, Bispecific ; },
abstract = {OBJECTIVE: To evaluate the efficacy of faricimab in various retinal conditions in previously treated patients.

METHODS: This study included patients who received at least three faricimab injections at a large medical center between April 2023 and October 2024, all of whom were not naive to treatment.

RESULTS: A total of 242 eyes from 219 patients were included in the analysis. The diagnoses were: 139 eyes with neovascular age-related macular degeneration (NVAMD), 63 eyes with diabetic macular edema (DME), 24 eyes with polypoidal choroidal vasculopathy (PCV), 5 eyes with choroidal neovascularization (CNV) secondary to central serous retinopathy (CSR), 5 eyes with branch retinal vein occlusion (BRVO) accompanied by cystoid macular edema (CME), 3 eyes with central retinal vein occlusion (CRVO) with CME, and 3 eyes with myopic CNV. Patients had previously received intravitreal injections of medications including bevacizumab, ranibizumab, aflibercept 2 mg, brolucizumab, triamcinolone, and Ozurdex. Following treatment with faricimab, the proportion of eyes with no intraretinal or subretinal fluid increased across all retinal diseases. Additionally, the average central subfield thickness decreased, the interval between injections was extended, and average visual acuity improved in every retinal condition. The average height of the pigment epithelium detachment (PED) decreased in cases of NVAMD and PCV.

CONCLUSIONS: Faricimab appears to be effective after the failure of other treatment options.},
}

Humans
Male
Female
Intravitreal Injections
*Retinal Diseases/drug therapy/diagnosis
Aged
Retrospective Studies
*Visual Acuity
Middle Aged
Angiogenesis Inhibitors/administration & dosage
Tomography, Optical Coherence
Treatment Outcome
Fluorescein Angiography
*Drug Substitution
Aged, 80 and over
Fundus Oculi
Follow-Up Studies
Antibodies, Bispecific

@article {pmid42068868,
year = {2026},
author = {Hammond, BR and Buch, J},
title = {The evidentiary basis and challenges associated with studying the role of light damage on ocular health.},
journal = {Journal of optometry},
volume = {19},
number = {3},
pages = {100616},
doi = {10.1016/j.optom.2026.100616},
pmid = {42068868},
issn = {1989-1342},
abstract = {The interaction between light and the eye is both essential and potentially harmful. Light regulates ocular development, supports vision, and influences systemic physiology, yet it can also induce photochemical damage. Determining whether chronic exposure to high-energy visible (HEV) light contributes to age-related ocular disease remains challenging. Randomized clinical trials, the gold standard for medical evidence, are largely infeasible for exposures that are lifelong, ubiquitous, and potentially harmful. Instead, researchers rely on a spectrum of evidence, from cellular and animal models to case studies, cohort studies, and expert consensus, each with unique advantages and limitations. This review categorizes existing evidence according to study design, evaluates its strengths and weaknesses, and considers how converging findings might inform clinical practice. We conclude that while acute light injury is well established, the long-term impact of low-level HEV exposure remains largely and necessarily inferential. Definitive evidence is difficult to obtain but improvements in exposure assessment and integration across different categories of evidence have led to a cautious but reasonable conclusion on the potential harms of long-term exposure.},
}

@article {pmid42069034,
year = {2026},
author = {Hekimsoy, HK and Şekeroğlu, MA and Ateşoğlu, Hİ and Doğuizi, S},
title = {The Foveal Microvasculature of Adult Offspring of Patients with Neovascular Age-Related Macular Degeneration.},
journal = {Photodiagnosis and photodynamic therapy},
volume = {},
number = {},
pages = {105497},
doi = {10.1016/j.pdpdt.2026.105497},
pmid = {42069034},
issn = {1873-1597},
abstract = {AIM: To assess the foveal microvasculature in adult offspring of patients with neovascular age-related macular degeneration (nAMD) who exhibit no clinical or imaging signs of AMD, and to compare these parameters with those of healthy controls without a family history of AMD.

METHODS: This cross-sectional study included 82 adult offspring of patients with nAMD and 85 age- and sex-matched controls. Optical coherence tomography angiography (OCTA) was used to evaluate vessel densities of the superficial and deep capillary plexuses (SCP and DCP), the foveal avascular zone (FAZ), outer retinal flow, and choriocapillaris (CCP) flow area.

RESULTS: There were no significant differences in demographic or visual parameters between groups, nor in FAZ area, perimeter, or acircularity index. However, vessel densities in all SCP and DCP zones, as well as outer retinal and CCP flow areas, were significantly reduced in the nAMD offspring group (all p < 0.05).

CONCLUSION: Subclinical microvascular alterations in SCP, DCP, and CCP were identified in clinically unaffected adult offspring of patients with nAMD. These findings suggest a potential heritable vascular component in early AMD pathogenesis and support the use of OCTA as a tool for risk stratification.},
}