@article {pmid41952137,
year = {2026},
author = {Park, HY and Joo, K and Woo, SJ},
title = {Therapeutic effect of faricimab in macular telangiectasia type 1 and Coats' disease: case series.},
journal = {BMC ophthalmology},
volume = {26},
number = {1},
pages = {},
pmid = {41952137},
issn = {1471-2415},
support = {RS-2025-02263279//Ministry of Health & Welfare, Republic of Korea/ ; },
abstract = {BACKGROUND: To report the anatomical and functional outcomes of intravitreal faricimab injection in cases of macular telangiectasia type 1 and Coats’ disease that were refractory to previous treatments.

METHODS: We describe four cases of macular telangiectasia type 1 and Coats’ disease with macular edema, which were treated with intravitreal faricimab injection.

RESULTS: Four patients with persistent cystoid macular edema despite prior treatment received intravitreal faricimab injections, and two of them showed anatomical and visual improvement. In case 1, a patient with Coats’ disease achieved improved telangiectatic vessel at macula and visual recovery following eight monthly injections of faricimab, with central macular thickness (CMT) reduced from 645 μm to 217 μm and BCVA improved from 20/30 to 20/25. In case 2, a patient with diabetic retinopathy and suspected macular telangiectasia type 1 showed improvement in CMT (670 μm to 219 μm) and visual acuity (20/63 to 20/40) with resolution of telangiectatic vessel with leakage after four faricimab injections. Case 3 and 4 were chronic and long-standing cases; in case 3, a patient with Coats’ disease demonstrated partial response with reduced macular edema, while in case 4, with a Coats’ disease, showed no response after two faricimab injections.

CONCLUSIONS: Faricimab may provide therapeutic benefits in cases of macular telangiectasia type 1 and Coats’ diseases unresponsive to previous anti-VEGF agents, potentially due to its dual inhibition of vascular endothelial growth factor-A and angiopoietin-2. However, its efficacy may be limited in patients with chronic phase. Further studies are warranted to assess its role in vascular retinal diseases beyond currently approved indications.},
}

@article {pmid42078357,
year = {2026},
author = {Hönes, GS and Liao, XH and Mahler, EA and Herrmann, P and Eckstein, A and Führer, D and Castillo, JM and Chiang, J and Vincent, AL and Weiss, RE and Dumitrescu, AM and Refetoff, S and Moeller, LC},
title = {THRB splice site variants lead to exon 4 skipping and TRβ1 gain-of-function syndrome.},
journal = {medRxiv : the preprint server for health sciences},
volume = {},
number = {},
pages = {},
pmid = {42078357},
abstract = {BACKGROUND: Heterozygous c.283+1G>A and c.283G>A variants in the THRB gene, encoding for thyroid hormone receptor (TR)β1 and β2, lead to autosomal dominant macular dystrophy (ADMD). We report the detailed clinical characterization of two first-degree relatives with ADMD, heterozygous for THRB c.283+1G>A, and an unrelated ADMD patient with a novel variant, c.283G>C. The genomic and molecular consequences of both variants were studied.

METHODS: gDNA and mRNA were obtained from leukocytes. Clinical characterization included biochemistry, bone density and body composition, ECG, echocardiography, ultrasound, audiometry and color-vision. In vitro assays investigated TR function and DNA binding.

RESULTS: The patients manifested no resistance to thyroid hormone beta (RTHβ) and had normal FT4 and TSH. Detailed studies in two patients showed no goiter, tachycardia, hypercholesterinemia or hepatic steatosis. Hearing was not impaired. Both had impaired color vision and reduced bone density. RT-PCR from all three patients revealed skipping of exon 4 exclusive to TRβ1, producing a deletion of 87 amino acids in the N-terminal domain (TRβ1[ΔNTD]). In vitro, DNA-binding affinity of TRβ1[ΔNTD] to DR4-TRE with or without RXRα was comparable to TRβ1[WT]. Surprisingly, TRβ1[ΔNTD] was transcriptionally twice more active than TRβ1[WT] with a similar EC50 for T3, demonstrating gain-of-function of TRβ1[ΔNTD]. THRA expression in leukocytes was increased by 3-fold compared to unrelated controls and different from RTHβ patients.

CONCLUSION: These THRB splice site variants produce TRβ1 exon 4 skipping, resulting in a gain-of-function mutant, TRβ1[ΔNTD]. This explains the dominant ADMD phenotype devoid of RTHβ and suggests a TRβ1 gain-of-function syndrome.},
}

@article {pmid42150558,
year = {2026},
author = {Zalke, J and Rotake, DR and Barve, VP and Rout, C and Singh, SG and Singh, R},
title = {Ultra-sensitive GO-MoS2/AuNPs hybrid biosensor for early-stage age-related macular degeneration via complement component C3 detection.},
journal = {Nanotechnology},
volume = {},
number = {},
pages = {},
doi = {10.1088/1361-6528/ae6f20},
pmid = {42150558},
issn = {1361-6528},
abstract = {Age-related macular degeneration (AMD) is a leading cause of vision loss, where early diagnosis remains critical for effective intervention. Complement Component 3 (C3) plays a central role in AMD pathogenesis, making it a promising biomarker for early-stage detection. In this study, we report an electrochemical immunosensor based on a graphene oxide-molybdenum disulfide/gold nanoparticle (GO-MoS2/AuNPs) hybrid nanocomposite for the ultrasensitive detection of C3 in tear samples via a non-invasive approach. The GO-MoS2 platform provides a high surface area with abundant functional groups for efficient antibody immobilization, while AuNPs enhance electron transfer and signal amplification. The sensor response was evaluated using electrochemical impedance spectroscopy, where antigen-antibody interactions modulate charge transfer resistance (Rct). The developed biosensor exhibits a wide linear detection range from 10 fg mL[-1] (1 x10-8 ppm) to 500 pg mL[-1] (5 x 10-4 ppm) and an ultralow theoretical limit of detection of 1.17 fg mL[-1], calculated using the 3.3σ/slope method. Additionally, a high sensitivity of 518.05 % (ΔRct/Rct) (g mL[-1])[-1] cm[-2] was achieved, indicating efficient signal transduction. These results demonstrate the strong potential of the proposed platform for rapid, sensitive, and non-invasive detection of C3, offering a promising strategy for early AMD diagnosis.},
}

@article {pmid42150954,
year = {2026},
author = {Chen, H and Tan, Q and Hu, Y and Liu, L and Liang, X and Hou, L},
title = {DAPL1 deficiency impairs autophagy in retinal pigment epithelium to drive age-dependent retinal pathologies.},
journal = {Journal of the Formosan Medical Association = Taiwan yi zhi},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.jfma.2026.05.038},
pmid = {42150954},
issn = {0929-6646},
abstract = {BACKGROUND/PURPOSE: Age-related retinopathy, mainly age-related macular degeneration (AMD), is a major cause of irreversible blindness in the elderly worldwide. Its precise mechanisms remain incompletely understood. Although autophagy deficiency in retinal pigment epithelial (RPE) cells is associated with AMD in patients, the regulatory pathways involved are still unclear. The research purpose is to investigate the functional role and underlying mechanism of DAPL1 in autophagy deficiency in the age-dependent retinal pathologies.

METHODS: In this study, 18-month-old wild-type (WT) and Dapl1[-/-] mice were used. Fundus photography and optical coherence tomography (OCT) were employed to detect morphological abnormalities. Immunofluorescence was performed to examine GFAP, Rhodopsin/Opsin, IBA1, and LC3, and on RPE flat mounts for ZO-1. Lipid deposition was analyzed by Oil Red O staining. To investigate downstream mediators of DAPL1, western and RT-qPCR were used to identify and validate candidate genes, followed by functional validation using lentiviral overexpression and RNA interference.

RESULTS: At 18 months of age, Dapl1-deficient mice exhibit age-related retinal dysfunction and structural abnormalities. These include increased retinal stress, damage to photoreceptors and RPE cells, lipid accumulation, and microglial activation. Autophagy is impaired in the RPE cells of Dapl1-deficient mice. DAPL1 overexpression in RPE cells enhances autophagy activity. Furthermore, DAPL1 suppresses the expression of E2F1 and c-MYC. This downregulates mTOR and upregulates the expression of ATG16 and Beclin1 through DAPK1 in RPE cells, promoting autophagy.

CONCLUSION: These findings suggest DAPL1 is a novel regulator of autophagy in RPE cells, and its deficiency increases susceptibility to age-dependent retinal pathologies in mice.},
}

@article {pmid42151388,
year = {2026},
author = {Miura, M and Trinh, M and Juan, EG and Shu, X},
title = {Macular degeneration collection.},
journal = {Scientific reports},
volume = {16},
number = {1},
pages = {},
pmid = {42151388},
issn = {2045-2322},
mesh = {Humans ; *Macular Degeneration/therapy/diagnosis/pathology ; },
abstract = {Age-related macular degeneration (AMD) remains a leading cause of severe vision loss among the older adults in developed countries. Improving patient outcomes is dependent on elucidating the complex pathogenesis of the disease and refining clinical and therapeutic strategies. This Collection showcases a diverse range of papers exploring the frontiers of imaging-based prediction, treatment optimization, mechanistic biology, and the assessment of visual function. Together, these studies provide critical insights to inform the next generation of AMD management.},
}

Humans
*Macular Degeneration/therapy/diagnosis/pathology

@article {pmid42152120,
year = {2026},
author = {Gong, J and Ghotbaldini, S and Viniak, R and Rajesh, A and Lavine, JA},
title = {Tissue-resident macrophages maintain choroidal homeostasis by complement dependent and independent mechanisms.},
journal = {Journal of neuroinflammation},
volume = {},
number = {},
pages = {},
doi = {10.1186/s12974-026-03872-6},
pmid = {42152120},
issn = {1742-2094},
support = {Unrestricted Departmental Grant//Research to Prevent Blindness/ ; Research and Education Award//The Retina Society/ ; EY034486/EY/NEI NIH HHS/United States ; CA060553/CA/NCI NIH HHS/United States ; 1S10OD032270-01A1/NH/NIH HHS/United States ; },
abstract = {BACKGROUND: Age-related macular degeneration (AMD) is characterized by disruption of the choriocapillaris (CC) and retinal pigment epithelium (RPE) dysfunction, leading to drusen accumulation. The CC and RPE form a tightly interdependent unit that maintains homeostasis where the CC supplies oxygen and nutrients to the RPE, while the RPE produces vascular endothelial growth factor (VEGF) to maintain the CC. Genetic studies link alternative complement pathway variants to AMD, and complement deposition on the CC increases during both aging and AMD. Macrophages express complement protein, receptors, and inhibitors, suggesting that they may be a missing link in understanding the role of complement in AMD. In support, previous groups have shown that macrophage depletion disrupts RPE-CC homeostasis, leading to AMD-like pathology, but the mechanism remains unclear.

METHODS AND RESULTS: To investigate the role of macrophages in CC-RPE homeostasis, we generated Cx3cr1[CreER]Csf1r[i-DTR] and Ms4a3[Cre]Rosa26[DTR] mice. In Cx3cr1[CreER]Csf1r[i-DTR] mice, tamoxifen administration induced diphtheria toxin receptor (DTR) expression, allowing ablation of all macrophages (many tamoxifen injections) or long-lived, tissue-resident macrophages (tamoxifen followed by a 3-4 week wash out period). Ms4a3[Cre]Rosa26[DTR] mice were used to deplete monocyte-derived macrophages. Ablation of all macrophages caused decreased CC density, increased CC apoptosis, RPE disorganization, and membrane attack complex (MAC) accumulation. Tissue-resident macrophage ablation phenocopied this result while monocyte-derived macrophage ablation had no phenotype. Additionally, long-term depletion of tissue-resident macrophages led to formation of drusen-like sub-RPE deposits and retinal thinning, mimicking AMD pathology. Finally, pharmacologic depletion of all macrophages similarly reduced CC density to genetic ablation, but C3[-/-] mice showed an attenuated phenotype.

CONCLUSIONS: These data demonstrate that long-lived, tissue-resident macrophages are essential for maintaining CC-RPE homeostasis while monocyte-derived macrophages are dispensable in this context. Further, ocular macrophage ablation led to MAC accumulation, while C3[-/-] mice were resistant to CC regression. Together, these findings suggest that tissue-resident choroidal macrophages maintain CC-RPE homeostasis partially by complement dependent mechanisms. Further, the loss of tissue-resident choroidal macrophages over time is a potential mechanism of AMD pathogenesis.},
}

@article {pmid42152481,
year = {2026},
author = {Cai, J and Jiang, Y and Liu, X and Yang, T and Yang, P and Chen, L},
title = {FASN mediates crosstalk between autophagy and lipid metabolism via the AMPK-MTOR pathway in early age-related macular degeneration.},
journal = {Autophagy},
volume = {},
number = {},
pages = {1-20},
doi = {10.1080/15548627.2026.2673559},
pmid = {42152481},
issn = {1554-8635},
abstract = {Age-related macular degeneration (AMD) involves sub-retinal pigment epithelium (sub-RPE) lipid deposition in the early stage, with dysregulated lipid metabolism and impaired macroautophagy/autophagy implicated, yet the molecular mechanisms underlying their interaction remain unclear. In this study, transcriptomic analysis of human macular tissues identified FASN (fatty acid synthase), a regulator of lipid metabolism and lysosomal function, as a significantly upregulated key hub gene in early AMD. In apoe[-/-] mice fed a high-fat diet (HFD), retina-RPE-choroid complexes revealed elevated FASN alongside autophagy suppression, lysosomal dysfunction, and lipid accumulation. In vitro, FASN protein levels increased in RPE cells treated with the autophagy inhibitor 3-methyladenine (3-MA), but decreased with the autophagy activator rapamycin (RAPA), without transcriptional changes; lysosomal blockade with chloroquine (CQ) induced FASN accumulation, which was significantly delayed following autophagy inhibition. These findings indicate that FASN accumulation results from insufficient autophagic degradation. Conversely, FASN knockdown or pharmacological inhibition enhanced autophagic flux and promoted lysosomal lipid clearance in RPE cells. Mechanistically, FASN inhibition increased AMPK phosphorylation and decreased MTOR activity, thereby facilitating autophagy and lipophagy. Collectively, our findings reveal a self-amplifying pathological circuit in early AMD: autophagy impairment drives FASN accumulation, which in turn exacerbates lysosomal dysfunction and lipid accumulation. Targeting the FASN-AMPK-MTOR axis may offer a promising therapeutic strategy for early AMD.},
}

@article {pmid42153784,
year = {2026},
author = {Estay-Ahumada, CE and Roux, M and Ciocca, D and El-Kholti, N and Birling, MC and Rossolillo, P and Felder-Schmittbuhl, MP and Hicks, D},
title = {Abca4 Knockdown in the Cone-Rich Rodent Psammomys Obesus Leads to Stargardt's Disease-Like Progressive Retinal Degeneration.},
journal = {Investigative ophthalmology & visual science},
volume = {67},
number = {5},
pages = {47},
doi = {10.1167/iovs.67.5.47},
pmid = {42153784},
issn = {1552-5783},
mesh = {Animals ; Gerbillinae ; *ATP-Binding Cassette Transporters/genetics ; Electroretinography ; Stargardt Disease/genetics ; Disease Models, Animal ; *Retinal Cone Photoreceptor Cells/metabolism/pathology ; Tomography, Optical Coherence ; *Macular Degeneration/genetics/congenital/metabolism ; *Retinal Degeneration/genetics/metabolism ; CRISPR-Cas Systems ; Gene Knockdown Techniques ; Genetic Vectors ; Dependovirus/genetics ; },
abstract = {PURPOSE: Mutations in the gene ABCA4 coding for photoreceptor-specific ATP-binding cassette subfamily A member 4, are responsible for Stargardts disease type 1 (STGD1), the most common form of inherited macular degeneration. We recently showed that injection of viral vectors expressing CRISPR/Cas9 tools directed against Abca4 into young Sand Rat (Psammomys obesus) eyes led to extensive structural and functional retinal degeneration resembling STGD1. Here we provide further evidence that this is highly likely due to specific knockdown of Abca4 and not off-target errors.

METHODS: We performed subretinal injections of Adeno-Associated Virus-CRISPR/Cas9-Abca4 constructs into postnatal (∼P15) Psammomys obesus. Eyes were examined by noninvasive exploration (ocular coherence tomography, fundus and electroretinography) at 15-60 days after injection. Additionally, subgroups were euthanized over the same time period, and ocular tissue was used for immunochemical analyses.

RESULTS: RNAscope analysis of injected eyes showed knockdown of Abca4, rhodopsin and cone transducin mRNA in transduced regions; neighbouring tissue that was not transduced showed robust expression of all three. Injection of control AAV, expressing CAS9 alone, induced only mild glial activation. Statistically significant decreases in visual responses to light flashes were only seen in eyes injected with the fully active CRISPR/Cas9-Abca4 probes.

CONCLUSIONS: Taken together, these data rule out off-target effects as responsible for the observed degeneration, and indicate that Psammomys obesus faithfully recapitulates many of the features seen in human STGD1, thus positioning it as an important research opportunity to further explore genotype-phenotype relationships and test putative therapeutic approaches.},
}

Animals
Gerbillinae
*ATP-Binding Cassette Transporters/genetics
Electroretinography
Stargardt Disease/genetics
Disease Models, Animal
*Retinal Cone Photoreceptor Cells/metabolism/pathology
Tomography, Optical Coherence
*Macular Degeneration/genetics/congenital/metabolism
*Retinal Degeneration/genetics/metabolism
CRISPR-Cas Systems
Gene Knockdown Techniques
Genetic Vectors
Dependovirus/genetics

@article {pmid42154370,
year = {2026},
author = {Benekos, K and Katsanos, A and Laspas, P and Panos, GD and Vagiakis, I and Fousekis, FS and Luca, R and Zhou, B and Kostoulas, C and Georgiou, I and Katsanos, KH and Skondra, D and Konstas, AG},
title = {An Update and Overview of the Ocular and Extraocular Microbiome and Its Impact on Ophthalmic Care.},
journal = {Advances in therapy},
volume = {},
number = {},
pages = {},
pmid = {42154370},
issn = {1865-8652},
abstract = {The microbiome has been described as the last human "organ" and is currently the topic of great research interest worldwide. The application of culture-independent methods, like 16S ribosomal next-generation sequencing, has offered researchers the opportunity to identify bacterial populations that were impossible to detect previously using conventional culture methods. Further standardization of these new approaches to characterizing the microbiome is desirable. The present review discusses the mounting evidence suggesting that alterations in the microbiome and microbial metabolites, such as short-chain fatty acids in the gut, mouth, and ocular surface, may play a key role in the pathogenesis of ocular pathologies such as ocular surface disease, glaucoma, uveitis, age-related macular degeneration, and diabetic retinopathy. Clarifying the probable role of the microbiome in ocular diseases would not only offer valuable insights into pathogenesis but could also enable the development of novel therapeutic approaches. As yet, microbial-based therapeutic applications in ophthalmology are limited. Nevertheless, recently emerging strategies utilizing probiotics and prebiotics, or even fecal transplantation to regulate microbiome composition, offer promising research avenues for developing future innovative therapies for ocular diseases. Further studies employing standardized methodological protocols are needed to ensure the reproducibility of results and to eventually unlock the precise links between the microbiome and the eye.},
}

@article {pmid42154378,
year = {2026},
author = {Matsumoto, H and Hoshino, J and Numaga, S and Asatori, Y and Akiyama, H},
title = {One-year outcomes of treat-and-extend regimen with intravitreal aflibercept 8 mg for treatment-naïve neovascular age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42154378},
issn = {1613-2246},
abstract = {PURPOSE: To evaluate 1-year outcomes of loading phase treatment followed by a treat-and-extend (TAE) regimen with intravitreal aflibercept 8 mg for neovascular age-related macular degeneration (nAMD).

STUDY DESIGN: Retrospective, interventional case series.

METHODS: We retrospectively studied 83 eyes of 80 consecutive patients with treatment-naïve nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), central choroidal thickness (CCT), total number of injections over 1 year, and intended injection interval at the last visit.

RESULTS: Sixty eyes (72.3%) completed the 1-year aflibercept 8mg treatment. Their BCVA improved significantly, with significant reductions in FT and CCT, for up to 1 year. The total number of injections was 6.5±0.7, and the intended injection interval at the last visit was 13.4±3.3 weeks. Of the 23 eyes (27.7%) failing to complete the 1-year treatment, 9 (10.8%) developed non-infectious intraocular inflammation (IOI) associated with retinal vasculitis during the loading phase, leading to treatment discontinuation. Moreover, 7 eyes (8.4%) were switched to intravitreal brolucizumab due to persistent exudation with an 8-week interval of aflibercept 8mg injections in the maintenance phase. The remaining 7 eyes (8.4%) dropped out.

CONCLUSIONS: Loading phase treatment followed by a TAE regimen with intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, there might be cases in which exudative changes cannot be adequately controlled with injections of aflibercept 8 mg. Moreover, careful monitoring is required due to the potential development of IOI associated with retinal vasculitis during the loading phase.},
}

@article {pmid42154379,
year = {2026},
author = {Yoneyama, S and Sakurada, Y and Fukuda, Y and Shijo, T and Kotoda, Y and Kikushima, W and Mabuchi, F and Kashiwagi, K},
title = {Genetic factors associated with response to as-needed brolucizumab treatment for exudative age-related macular degeneration.},
journal = {Japanese journal of ophthalmology},
volume = {},
number = {},
pages = {},
pmid = {42154379},
issn = {1613-2246},
abstract = {PURPOSE: To investigate the association between genetic variants susceptible to exudative age-related macular degeneration (AMD) and the treatment response to as-needed intravitreal brolucizumab (IVBr) therapy.

STUDY DESIGN: Interventional study METHODS: This retrospective study included 103 treatment-naïve eyes with exudative AMD. All eyes received three monthly IVBr injections (6.0 mg/0.05 mL) followed by a pro re nata regimen for 12 months. Seven major AMD-associated single nucleotide polymorphisms-ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH rs1329428, C2-CFB-SKIV2L rs429608, C3 rs2241394, CETP rs3764261, and ADAMTS9 rs6795735-were genotyped using TaqMan assays. The requirement for retreatment, the number of additional injections, and visual outcomes were compared across genotypes.

RESULTS: Of the 103 patients, 68 (66.0%) required additional injections. The T allele of ARMS2 A69S was significantly more frequent in the retreatment group than in the retreatment-free group (65.0% vs. 42.9%, p = 1.9 × 10⁻[3]) and remained independently associated with retreatment after adjustment for age, sex, and baseline visual acuity (p = 3.0 × 10⁻[3]). Eyes with the TT genotype required significantly more additional injections than those with the TG or GG genotypes (2.4 ± 1.7 vs. 1.3 ± 1.6 and 1.3 ± 1.5, respectively; p = 5.0 × 10⁻[3]). Kaplan-Meier analysis demonstrated a significant difference in retreatment-free survival among ARMS2 genotypes (p = 4.1 × 10⁻[4]). Visual outcomes did not differ across any genotypes.

CONCLUSIONS: ARMS2 A69S may serve as a predictor of recurrence and number of additional injections in as-needed brolucizumab therapy for exudative AMD.},
}

@article {pmid42154394,
year = {2026},
author = {Spartalis, C and Ullrich, M and Winkler, S and Leisser, C and Ruiss, M and Pilwachs, C and Findl, O},
title = {Prospective Real-World Outcomes After Switching to Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration with High Treatment Burden.},
journal = {Ophthalmology and therapy},
volume = {},
number = {},
pages = {},
pmid = {42154394},
issn = {2193-8245},
abstract = {INTRODUCTION: This study aimed to evaluate functional, anatomical, and safety outcomes after switching from aflibercept 2 mg to aflibercept 8 mg in patients with neovascular age-related macular degeneration (nAMD) requiring short re-treatment intervals in a real-world setting.

METHODS: This single-center prospective observational study included patients with nAMD insufficiently responsive to prior anti-vascular endothelial growth factor (anti-VEGF) therapy requiring re-treatment every 4-6 weeks. All eyes had received four consecutive intravitreal injections of aflibercept 2 mg prior to switching to aflibercept 8 mg as part of routine clinical management. Functional outcome was assessed by distance-corrected visual acuity (DCVA). Anatomical outcomes included central retinal thickness (CRT), central subfield thickness (CST), and optical coherence tomography (OCT) features. Injection burden, responder status, discontinuation, and safety outcomes were evaluated. Follow-up occurred at 3, 6, 9, and 12 months.

RESULTS: Fifty patients (50 eyes) were included (mean age 78.4 ± 6.9 years; 60% female). Median baseline DCVA was 0.19 logMAR (IQR 0.12-0.32; 75.5 ETDRS letters), median CST 272 µm, and median CRT 338 µm. DCVA improved significantly at months 3, 6, and 9 (p ≤ 0.046) and remained stable at month 12. CRT and CST decreased early and remained improved. Over 12 months, 24 patients (48%) completed follow-up, while 26 (52%) discontinued early. Intraocular inflammation (IOI) occurred in 10 eyes (20%), corresponding to 3.0% per injection, and was temporally associated with off-label aliquoted preparation; all cases resolved without permanent visual loss. No further IOI events were observed after transition to on-label preparation. During safety evaluation, seven patients discontinued aflibercept 8 mg as a result of precautionary safety measures. Seventeen (34%) required ≤ 8 injections per year.

CONCLUSIONS: In chronically treated patients with nAMD requiring short re-treatment intervals, switching to aflibercept 8 mg was associated with modest anatomical improvement and stable visual function. A reduction in treatment burden was observed in a subset of patients, although overall durability remained heterogeneous and discontinuation rates were high. A cluster of sterile inflammatory events occurred during off-label aliquoted preparation, highlighting the importance of appropriate drug handling. Careful patient selection and strict adherence to on-label preparation procedures are essential to optimize safety. These findings should be interpreted cautiously given the exploratory design, lack of a comparator group, and high discontinuation rate.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT07390253.},
}

@article {pmid42155048,
year = {2026},
author = {Sbrana, F and Dal Pino, B and Schettler, VJJ and Muso, E and Harada-Shiba, M and Di Mola, M and Kagitani, M and Pineda, E and Selke, N and Jenke, S and Zimmermann, T and Bernhardt, W and Bigazzi, F and Heigl, F and Grützmacher, P and Löhlein, I and Klingel, R and Corciulo, C and Hohenstein, B and Ramlow, W and Vogt, A and Ramunni, A and Emdin, M and Sampietro, T and Julius, U and Schlieper, G and Stefanutti, C and Moriarty, PM},
title = {Lipoprotein apheresis in the era of new lipid-lowering therapies.},
journal = {European heart journal},
volume = {},
number = {},
pages = {},
doi = {10.1093/eurheartj/ehag328},
pmid = {42155048},
issn = {1522-9645},
abstract = {During the 1960s, in a pioneering way, plasmapheresis was used to treat children with homozygous familial hypercholesterolaemia (HoFH). Over the years, apheresis has evolved to increasingly selective methods, which have been used in paediatric HoFH since the 1990s. Today, lipoprotein apheresis (LA) is able to selectively remove atherogenic apoB100-containing lipoproteins from the blood: the main component of LDL-cholesterol, VLDL-cholesterol, and lipoprotein(a). Lipoprotein apheresis has demonstrated protective effects in the endothelium and microcirculation, prevention of the development of new aortic and coronary lesions in HoFH, reducing the incidence of major cardiovascular events, and proving helpful in subjects who fail to reach the LDL-cholesterol target or who have elevated lipoprotein(a) levels in secondary prevention. Although advances in pharmacological therapies (proprotein convertase subtilisin/kexin Type 9 inhibitors, antisense oligonucleotides, and siRNA-based treatments) have expanded the options for lipid management, LA remains a safe therapeutic approach for patients with severe lipid disorders, including HoFH, to reduce their cardiovascular risks. Currently, to put LA into perspective, some obstacles need to be overcome, including (i) the underdiagnosis of HoFH and high lipoprotein(a) level; (ii) therapeutic inertia resulting from the use of new lipid-lowering drugs with partial achievement of lipid targets; and (iii) availability of qualified LA centres and practitioners. Further prospective studies may prove useful to identify other therapeutic scenarios for LA, such as renal disease, diabetic foot ulcer, peripheral arterial disease, pre-eclampsia, macular degeneration, or sudden sensorineural hearing loss. In these clinical settings, prospective, randomized clinical trials are therefore warranted.},
}

@article {pmid42156503,
year = {2026},
author = {Diaz-Marin, R and Hata, M and Guber, V and De Guire, V and Wilson, AM and Crespo-Garcia, S and Sapieha, P},
title = {Adipocytes influence choroidal neovascularization via PRDM16.},
journal = {EMBO molecular medicine},
volume = {},
number = {},
pages = {},
pmid = {42156503},
issn = {1757-4684},
support = {183779//Canadian Institutes of Health Research (CIHR)/ ; 529136//Canadian Institutes of Health Research (CIHR)/ ; M2022015I//BrightFocus Foundation (BFF)/ ; },
abstract = {Neovascular age-related macular degeneration (nAMD) is a prominent cause of blindness in the elderly, characterized by pathological subretinal choroidal neovascularization (CNV). While age and genetics predispose to AMD, modifiable factors such as body adiposity are also thought to contribute. In a mouse model of nAMD, we identified a role for adipose tissue (AT) in exacerbating CNV, specifically pathways in adipocytes expressing Prdm16. Laser-induced CNV in the retina led to heightened expression of genes associated with browning and inflammation in distal inguinal white AT (iWAT). Selective deletion of the browning-associated transcription factor Prdm16 in adipocytes inhibited AT browning and reduced CNV. Reintroduction of Prdm16-expressing adipose tissue was sufficient to aggravate CNV in Prdm16-deficient mice. Ex vivo experimentation suggested that Prdm16-expressing adipocytes secrete angiogenic factors such as IGFBP5 and contribute to pathological angiogenesis. Thus, Prdm16-expressing adipocytes contribute to CNV, highlighting communication between the retina and distal tissues in the pathogenesis of AMD.},
}

@article {pmid42139589,
year = {2026},
author = {Xiao, J and Yavari, N and Nimmagadda, H and Mruthyunjaya, P and Rahimy, E and Smith, SJ and Ludwig, CA and Koo, E and Wai, KM},
title = {Association Between Mental Health Disorders in Age-Related Macular Degeneration: A Cohort Study Using a Global Health Records Network.},
journal = {Ophthalmic surgery, lasers & imaging retina},
volume = {57},
number = {5},
pages = {301-308},
doi = {10.3928/23258160-20260311-02},
pmid = {42139589},
issn = {2325-8179},
mesh = {Humans ; Female ; Aged ; Male ; *Mental Disorders/epidemiology/etiology ; *Wet Macular Degeneration/complications/epidemiology ; Aged, 80 and over ; Retrospective Studies ; Risk Factors ; *Macular Degeneration/complications ; Electronic Health Records ; Global Health ; Middle Aged ; Propensity Score ; Angiogenesis Inhibitors ; },
abstract = {BACKGROUND AND OBJECTIVE: This study assessed risk of mental health disorders in patients with age-related macular degeneration (AMD).

PATIENTS AND METHODS: Data were obtained from an aggregated electronic health records database. Patients who were diagnosed with AMD with cataract were propensity score-matched with cataract controls. Diagnoses were identified using International Classification of Diseases, 10th Revision (ICD-10) codes. Subgroup analyses evaluated relative risk (RR) of new diagnoses of mental health disorders among patients with dry AMD, neovascular AMD (nAMD), vision impairment, and receipt of intravitreal therapy.

RESULTS: After matching, 126,799 cases comprising 53.1% female patients with a mean age of 74.6 ± 8.9 years were included. Patients with AMD and cataract had elevated risk of receiving diagnoses of depression (RR = 1.27; 95% CI 1.24-1.29) and anxiety (RR = 1.19; 1.17-1.22). These patients were also at increased risk for self-harm (RR = 1.16), substance use (RR = 1.10), dysthymia (RR = 1.41), and psychosis (RR = 1.22) (all P < .05). The presence of visual impairment amplified these risks, particularly for depression (RR = 1.97) and anxiety (RR = 1.62). Patients with dry AMD had an increased risk of depression and anxiety compared to those with nAMD. Treatment with intravitreal injections in nAMD patients was associated with decreased risk of depression (RR = 0.88) and anxiety (RR = 0.82).

CONCLUSIONS: AMD is associated with increased risk of mental health disorders, including anxiety, depression, and self-harm, particularly in the first year following diagnosis. Risk varies by disease subtype, visual function, and treatment status.},
}

Humans
Female
Aged
Male
*Mental Disorders/epidemiology/etiology
*Wet Macular Degeneration/complications/epidemiology
Aged, 80 and over
Retrospective Studies
Risk Factors
*Macular Degeneration/complications
Electronic Health Records
Global Health
Middle Aged
Propensity Score
Angiogenesis Inhibitors

@article {pmid42142069,
year = {2026},
author = {Kim, H and Joe, BH and Nam, D and Yoo, TK},
title = {Oculomics of lipid metabolism: A scoping review across anterior and posterior segment diseases.},
journal = {Science progress},
volume = {109},
number = {2},
pages = {368504261453276},
pmid = {42142069},
issn = {2047-7163},
mesh = {Humans ; *Lipid Metabolism ; *Dyslipidemias/metabolism ; *Eye Diseases/metabolism ; Biomarkers/metabolism ; Macular Degeneration/metabolism ; },
abstract = {Dyslipidemia comprises interacting disturbances in lipids and lipoproteins that track with metabolic status, vascular biology, and inflammation. Ocular imaging offers scalable, quantifiable phenotypes to interrogate lipid-related pathways and to develop oculomics. We conducted a scoping review to map evidence linking dyslipidemia and lipid-related biomarkers with ocular phenotypes across the ocular surface, lens, macula, retinal microvasculature, and vascular occlusive disease, and to consider implications for AI-based risk modeling. We searched PubMed, Embase, Scopus, and Web of Science, supplemented by reference screening, and charted lipid exposures such as LDL-C, non-HDL-C, apoB/apoA-I, and the triglyceride-glucose index. The biologically grounded patterns were observed in macular disease, where cholesterol- and apolipoprotein-related material within the RPE-Bruch's membrane complex and drusen-related phenotypes support lipid-handling and innate immune pathways in age-related macular degeneration. Retinal vascular phenotypes showed generally consistent signals compatible with endothelial stress and microvascular remodeling. Epidemiologic associations were apparent in metabolically co-traveling conditions such as meibomian gland dysfunction and diabetic retinopathy, in which triglyceride-rich dyslipidemia and insulin resistance markers were often more informative than LDL-C alone and associations were often non-linear or interaction-dependent. By contrast, findings for glaucoma and cataract were modest and inconsistent, while vascular occlusive phenotypes clustered with broader atherosclerotic risk. Statin associations varied by outcome and were vulnerable to confounding. Predicting individual lipid analytes from retinal images appears limited, whereas integrated ocular signatures may support cardiovascular risk stratification. Future studies should refine phenotype definitions, model non-linearity, account for lipid-lowering therapy, and prospectively validate multimodal oculomics and AI across devices and populations.},
}

Humans
*Lipid Metabolism
*Dyslipidemias/metabolism
*Eye Diseases/metabolism
Biomarkers/metabolism
Macular Degeneration/metabolism

@article {pmid42144178,
year = {2026},
author = {Nguyen, VP and Zheng, M and Lee, Y and Park, S and Dang, C and Tran, K and Wei, Z and Yang, D and Paulus, YM},
title = {A Low-Cost, Tunable Suprachoroidal Injection Platform with Real-Time OCT Guidance for Gene Therapy Delivery.},
journal = {Experimental eye research},
volume = {},
number = {},
pages = {111060},
doi = {10.1016/j.exer.2026.111060},
pmid = {42144178},
issn = {1096-0007},
abstract = {Gene therapy shows considerable promise for treating vision impairments, including retinitis pigmentosa (RP), age-related macular degeneration (AMD), and diabetic retinopathy (DR). Current delivery methods, such as subretinal, intravitreal, and conventional suprachoroidal injections, are effective but pose significant challenges, including inflammation and complications that hinder their clinical translation. In this study, we present an integrated suprachoroidal injection (SCI) platform that combines a low-cost, tunable needle design with real-time optical coherence tomography (OCT) guidance for precise and safe suprachoroidal delivery. The injection device is constructed from a standard insulin syringe fitted with an adjustable silicone sheath that enables rapid and continuous control of needle penetration depth, eliminating the need for complex nested-needle assembly used in prior approaches. Real-time spectral-domain OCT imaging was incorporated to dynamically monitor needle positioning and confirm suprachoroidal delivery. In vivo studies in rabbits demonstrated accurate delivery of indocyanine green (ICG) and adeno-associated virus (AAV) vectors without ocular or systemic toxicity. Furthermore, AAV delivery exhibited dose-dependent transgene expression over 28 days, validating the platform for gene therapy applications. Compared with existing microneedle and catheter-based systems, this approach offers a simplified, scalable, and cost-effective alternative while maintaining precision through imaging guidance. This combined platform provides a practical solution for suprachoroidal drug delivery and facilitates broader adoption in both preclinical and translational research.},
}

@article {pmid42147074,
year = {2026},
author = {Nowosielska, AJ and Rotuski, G},
title = {Impact of treatment gap on visual acuity in patients with submacular hemorrhage secondary to neovascular age-related macular degeneration treated with quadruple intervention strategy.},
journal = {Therapeutic advances in ophthalmology},
volume = {18},
number = {},
pages = {25158414261447184},
pmid = {42147074},
issn = {2515-8414},
abstract = {BACKGROUND: Submacular hemorrhage (SMH) is an uncommon complication of neovascular age-related macular degeneration (AMD).

OBJECTIVES: The study aim was to evaluate the efficacy of combination therapy vitrectomy with subretinal recombinant tissue plasminogen activator (rtPA) given under the retina and anti-VEGF given into the vitreous cavity in patients with SMH based on duration of symptoms and to identify biomarkers to help predict potential visual acuity gain after the procedure.

DESIGN: Retrospective case series.

METHODS: Patients with SMH secondary to AMD were treated with quadruple therapy: (1) vitrectomy; (2) rtPA administration; (3) bevacizumab injection into the vitreous cavity; followed by (4) monthly intravitreal double-dose bevacizumab 2.5 mg.

RESULTS: Forty-eight patients were treated (68.8% women; mean age, 80 years). A median of 14 days elapsed between SMH onset and surgical intervention (range, 2-120 days), with vitrectomy performed after ⩾30 days in 39.6% of patients. A significant improvement from baseline in mean best-corrected visual acuity (BCVA) was observed 6 months after SMH treatment (1.6 (baseline) vs 0.9 (Month 6) logMAR; p < 0.001). Overall, 46 (95.8%) patients had improved BCVA and two (4.2%) had stable (unchanged) BCVA in the treated eye. Improvement in BCVA at Month 6 was similar between the cohort with only SMH and patients with coexisting subretinal pigment epithelium hemorrhage (p = 0.11). The main biomarkers predicting surgical outcome were the state of the retina in the foveal center point and hemorrhage thickness. Treatment ⩾30 days after SMH onset resulted in poorer BCVA at Month 6 compared with treatment occurring <30 days after onset (p < 0.05).

CONCLUSION: A combination of vitrectomy, subretinal rtPA, and bevacizumab, performed in patients with submacular hemorrhage due to neovascular AMD, followed by monthly intravitreal double-dose bevacizumab for SMH, was an effective intervention to achieve visual acuity improvement.},
}

@article {pmid42147450,
year = {2026},
author = {Gurnani, B and Kaur, K},
title = {Artificial intelligence in ophthalmology: from innovation to clinical integration.},
journal = {Frontiers in ophthalmology},
volume = {6},
number = {},
pages = {1839194},
pmid = {42147450},
issn = {2674-0826},
abstract = {Artificial intelligence (AI) has emerged as a transformative force in modern ophthalmology, enabling rapid advances in disease detection, clinical decision support, workflow optimization, and tele-ophthalmology. Ophthalmology is particularly suited for AI integration because of its reliance on imaging modalities such as fundus photography, optical coherence tomography (OCT), and visual field testing. Over the past decade, deep learning algorithms have demonstrated high diagnostic accuracy in identifying retinal diseases including diabetic retinopathy, age-related macular degeneration, and glaucoma. The approval of autonomous AI diagnostic systems for diabetic retinopathy screening marked a significant milestone in clinical adoption. Beyond diagnostics, AI is increasingly influencing surgical planning, predictive analytics, education, and patient engagement. Despite these promising advances, significant challenges remain regarding algorithm generalizability, ethical considerations, regulatory approval, data privacy, and integration into routine clinical practice. This perspective article reviews current innovations in AI applications within ophthalmology and discusses their clinical impact while outlining future directions for research and implementation. We argue that the next phase of AI in ophthalmology will involve multimodal learning systems, integration with large language models, and deployment in global eye-care networks to address disparities in access to care. A collaborative approach involving clinicians, data scientists, regulators, and industry will be essential to ensure safe, ethical, and effective adoption of AI technologies in ophthalmic practice.},
}

@article {pmid42147501,
year = {2026},
author = {Karagiannis, D and Bouratzis, N and Kontomichos, L and Batsos, G and Paroikakis, E},
title = {Prognosis and Treatment Approach for Stage 1 Retinal Angiomatous Proliferation Lesions: A Case Series With Long-Term Follow-Up.},
journal = {Cureus},
volume = {18},
number = {4},
pages = {e107009},
pmid = {42147501},
issn = {2168-8184},
abstract = {Retinal angiomatous proliferation (RAP) accounts for approximately 10%-20% of all neovascular (wet) age-related macular degeneration and is classically classified into three stages, with stage 1 representing the earliest form of disease. Despite its clinical relevance, limited evidence exists on the long-term prognosis of treatment-naïve stage 1 RAP, particularly regarding recurrence patterns and the development of macular atrophy or fibrosis over extended follow-up. This retrospective case series evaluates outcomes in four patients diagnosed with stage 1 RAP using optical coherence tomography (OCT) and fluorescein angiography. All patients were planned to receive a loading regimen of three monthly intravitreal aflibercept injections, followed by monthly review for at least 24 months. The loading phase was modified according to findings at each visit. At every appointment, best-corrected visual acuity (BCVA), slit-lamp examination, and OCT assessment of macular anatomy were performed, with recurrence defined as clinical and/or OCT evidence of exudative activity warranting re-treatment. Over the follow-up period, all four patients demonstrated stable or improved BCVA after anti-vascular endothelial growth factor (VEGF) therapy. Two patients had no recurrences across 24 months, while two patients each experienced a single recurrence, occurring at seven months and 24 months, respectively. Importantly, no eyes developed macular atrophy or fibrotic scarring during the observation period, and visual acuity remained stable or improved in all cases. These findings support the concept that early identification and prompt treatment of stage 1 RAP may be associated with a low recurrence burden and a favourable anatomic course, potentially limiting progression to atrophy or fibrosis and preserving long-term vision. They also suggest that a personalised management strategy, combining an initial loading phase with close surveillance and re-treatment only upon recurrence, may be effective in carefully selected early-stage RAP patients and could reduce overall injection burden. Larger studies with longer follow-up are required to confirm these preliminary observations and to better define stage-specific treatment strategies for RAP.},
}

@article {pmid42148323,
year = {2026},
author = {Jiang, L and Cuomu, G and Jijia, S and Yang, Y and Liu, J and Tao, Y},
title = {Crosstalk between endoplasmic reticulum stress and mitochondrial homeostasis: A new perspective on ophthalmic disease treatment.},
journal = {Journal of cell communication and signaling},
volume = {20},
number = {},
pages = {e70080},
pmid = {42148323},
issn = {1873-9601},
abstract = {Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are hallmarks of many ophthalmic diseases; however, they have traditionally been examined as isolated pathological processes. Recent evidence indicates that these organelles are inextricably coupled through mitochondria-endoplasmic reticulum contact sites, also known as mitochondria-associated membranes (MAMs), which coordinate Ca[2+] signaling, lipid transfer, mitochondrial dynamics, redox balance, and cell death decisions. Consequently, dysregulated ER-mitochondria communication has emerged as a key vulnerability that links the cellular stress responses among diverse ocular tissues, including lens epithelial cells, retinal ganglion cells, the retinal pigment epithelium, and corneal endothelial cells. In this review, we summarize the recent advances involving the molecular architecture and regulatory function of ER-mitochondria crosstalk. We focus on how the unfolded protein response signaling, pathological MAM remodeling, Ca[2+] dysregulation, and disrupted mitochondrial quality control collectively drive disease progression. By integrating evidence from cataract, glaucoma, diabetic retinopathy, age-related macular degeneration, and Fuchs endothelial corneal dystrophy, we reveal that these disorders are not driven by a uniform mechanism of organelle failure, but rather by the dominance of pathological nodes along the ER-mitochondria axis. We propose that ophthalmic diseases should be stratified based on these distinct failure nodes, which provides a mechanistic framework for developing therapeutics. Within this context, interventions targeting maladaptive ER stress, MAM destabilization, bioenergetic failure, or defective mitophagy should be considered complementary and context-dependent strategies. By reframing ophthalmic disorders as diseases of inter-organelle stress integration, this review positions the ER-mitochondria axis as a modifiable upstream determinant of ocular cell fate, which provides a foundation for stage-specific precision therapies.},
}

@article {pmid42149082,
year = {2026},
author = {Chen, PJ and Wan, L and Yip, HT and Tien, PT and Wang, IM and Tsai, FJ and Huang, YT and Lin, HJ},
title = {Bidirectional Association Between Age-Related Macular Degeneration and Cardiovascular Disease: A Population-Based Cohort Study in Taiwan with 15-Year Follow-up.},
journal = {Ophthalmic epidemiology},
volume = {},
number = {},
pages = {1-9},
doi = {10.1080/09286586.2026.2675291},
pmid = {42149082},
issn = {1744-5086},
abstract = {PURPOSE: To investigate the bidirectional association between age-related macular degeneration (AMD) and cardiovascular disease (CVD), including acute myocardial infarction (AMI) and ischemic stroke (IS), in a large Taiwanese cohort.

METHODS: We conducted a retrospective cohort study using electronic health records from China Medical University Hospital (CMUH), Taiwan. From 2003 to 2014, we identified 9,333 AMD patients with 37,332 matched controls, and 26,897 CVD patients with 107,588 matched controls. All patients were followed through December 31, 2019. Multivariable Cox regression was used to estimate the risk of CVD in AMD patients and the risk of AMD in CVD patients. The effects of common cardiovascular medications were also analyzed.

RESULTS: AMD patients had an increased risk of AMI (adjusted HR = 1.45, 95% CI = 1.25-1.69) and IS (adjusted HR = 1.78, 95% CI = 1.52-2.09) compared to controls. CVD patients had a higher risk of AMD (adjusted HR = 2.57, 95% CI = 1.30-5.09). Aspirin use among CVD patients was associated with a lower risk of AMD (HR = 0.69, 95% CI = 0.50-0.94). Several comorbidities, including diabetes, hypertension, and chronic kidney disease, further increased risks in both directions.

CONCLUSION: This population-based study demonstrates a significant bidirectional association between AMD and CVD in Taiwan. Integrated screening and management should be considered for patients with either condition.},
}

@article {pmid42149141,
year = {2026},
author = {Purola, P and Hujanen, P and Uusitalo, H and Uusitalo-Järvinen, H},
title = {Impact of delayed appointments on treatment outcomes in neovascular macular degeneration.},
journal = {Acta ophthalmologica},
volume = {},
number = {},
pages = {},
doi = {10.1111/aos.70169},
pmid = {42149141},
issn = {1755-3768},
support = {//Tampere University Hospital Support Foundation/ ; //The Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital/ ; //The Finnish Eye Foundation/ ; //State Funding for University-Level Health Research, Tampere University Hospital, Wellbeing Services County of Pirkanmaa/ ; //Suomen Kulttuurirahasto/ ; //Sokeain Ystävät/ ; //Finnish Federation of the Visually Impaired/ ; },
abstract = {PURPOSE: To evaluate the real-world visual outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy, the frequency of delayed appointments and the relationship between delays and visual outcomes in patients with neovascular age-related macular degeneration (nAMD).

METHODS: This single-centre retrospective study included a cohort of 3831 treatment-naïve nAMD patients who were treated with bevacizumab monotherapy using a pro re nata protocol between 2008 and 2023, comprising a total of 79 545 visits. Visual acuity (VA) was measured at the time of diagnosis and during follow-up visits and was converted into Early Treatment Diabetic Retinopathy Study letters. One eye per patient was included in the analysis. Delayed visits were categorised as >6 weeks and ≤8 weeks, >8 weeks and ≤ 10 weeks and >10 weeks.

RESULTS: After an initial stabilisation in VA during the first treatment year, VA started to decline. The proportion of visits delayed >6 weeks varied between 24% and 36% per treatment year, with delays being more common during the early years of the study when the new therapies were introduced. In general, the decline in VA was more severe with a higher number and longer duration of delayed visits.

CONCLUSIONS: Delays in anti-VEGF injections are common and strongly associated with vision loss. Therefore, it is important to improve patient awareness and compliance. Use of new longer-acting therapies may support this process.},
}

@article {pmid42138654,
year = {2026},
author = {Pierre-Henry, G and Creuzot-Garcher, C},
title = {Re: Shaheen et al: Efficacy and Safety of Anti-VEGF Injections and Surgery for Age-Related Macular Degeneration-Related Submacular Hemorrhage: A Systematic Review and Meta-analysis (Ophthalmol Retina. 2025;9:4-12).},
journal = {Ophthalmology. Retina},
volume = {},
number = {},
pages = {},
doi = {10.1016/j.oret.2026.04.015},
pmid = {42138654},
issn = {2468-6530},
}

@article {pmid42139166,
year = {2026},
author = {Lim, JI and Leng, T and Siedlecki, J and Lupidi, M and Wells, JA and Keane, PA and Nudleman, E and Mar, F and Gibson, K and Margaron, P and Tabano, D and Bührer, C and Holekamp, N},
title = {A Matching-Adjusted Comparison of Faricimab and Aflibercept 8 mg in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.},
journal = {Ophthalmic research},
volume = {},
number = {},
pages = {1-14},
doi = {10.1159/000552388},
pmid = {42139166},
issn = {1423-0259},
abstract = {INTRODUCTION: Matching adjusted network meta-analyses (NMA) provide an established method to indirectly compare treatments across trials that share a common comparator. In this exploratory analysis, we conducted a matching-adjusted NMA to compare the efficacy of faricimab with aflibercept 8 mg for treatment of diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) via the common comparator of aflibercept 2 mg during the first 12 weeks of treatment when all agents are dosed equally.

METHODS: Weighting was applied to match patient populations from YOSEMITE/RHINE (NCT03622580/NCT03622593) and TENAYA/LUCERNE (NCT03823287/NCT03823300) based on their baseline characteristics to published aggregated baseline characteristics for PHOTON (NCT04429503) and PULSAR (NCT04423718), respectively. The matched populations were used to recalculate outcomes from faricimab trials and an NMA anchored to aflibercept 2 mg was conducted. The analysis focused on change in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study letters and central subfield thickness (CST) in µm during the first 12 weeks of treatment when dosing was every 4 weeks for all three agents. Results are expressed as mean difference in change in BCVA or CST for each aflibercept dose.

RESULTS: For nAMD, BCVA change was similar between faricimab and aflibercept 2 mg and 8 mg, whereas CST reduction was greater for faricimab versus aflibercept 8 mg (-17.0 µm; 95% credible interval [CrI], -25.0, -8.4) and 2 mg (-19.0 µm; 95% CrI, -24.0, -13.0). For DME, BCVA change from baseline at 12 weeks was similar between faricimab and aflibercept 2 mg and 8 mg, while CST reduction was greater for faricimab versus aflibercept 8 mg (-19.0 µm; 95% CrI, -35.0, -3.2) and 2 mg (-19.0 µm; 95% CrI, -27.0, -12.0).

CONCLUSION: This matching-adjusted NMA indicated that dual angiopoietin-2/vascular endothelial growth factor (VEGF)-A inhibition with faricimab was associated with greater retinal drying during the matched-dosing phase in patients with nAMD and DME. Early dual pathway inhibition may therefore improve outcomes beyond anti-VEGF monotherapy.},
}

@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.},
}